Depression is associated with discoordination between heart rate variability and physical acceleration in older women.

Background and Aims: It is well known that depression is closely associated with the autonomic nervous system and physical acceleration (PA), which may cause functional time-deviance between these two parameters. Exploring this relationship is important in sustaining the mental and physical health of older adults in daily life. However, few studies have assessed the relationship between depression and the coordination of parasympathetic nervous activity (PSNA) and PA. The present study was designed to investigate whether the coordination between PSNA and PA is associated with the mental state of healthy volunteers in normal daily lives and the underlying mechanism. Methods: In total, 95 adult women were divided into non-older and older groups comprising 50 (aged 20-59 years) and 45 (aged 60-85 years) women, respectively. PSNA and PA data were simultaneously obtained every minute for 24 h during the free-moving day using the ActiveTracer accelerometer. Lag time was determined as the time difference between PSNA and PA, and it was introduced as a parameter of %lag0, which is the percent ratio of the lag = 0 min between PSNA and PA in 1 h. The General Health Questionnaire 28 (GHQ28) was used to evaluate the effects of psychological distress, including depression. Results: In the hour before sleep, %lag0 was significantly lower in older women (38.7 ± 6.4) who had higher GHQ28 values (subscale D = 0, n = 12) compared with that in older women (19.4 ± 10.5) with lower values (subscale D ≧ 1, n = 33) (p < 0.05). Conclusion: Impairments in coordination between PSNA and PA are significantly associated with depression in older women, particularly in the hour before sleep on free-moving days.

Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine.

Fibroblast activation proteins (FAP) are overexpressed in the tumor stroma and have received attention as target molecules for radionuclide therapy. The FAP inhibitor (FAPI) is used as a probe to deliver nuclides to cancer tissues. In this study, we designed and synthesized four novel 211At-FAPI(s) possessing polyethylene glycol (PEG) linkers between the FAP-targeting and 211At-attaching moieties. 211At-FAPI(s) and piperazine (PIP) linker FAPI exhibited distinct FAP selectivity and uptake in FAPII-overexpressing HEK293 cells and the lung cancer cell line A549. The complexity of the PEG linker did not significantly affect selectivity. The efficiencies of both linkers were almost the same. Comparing the two nuclides, 211At was superior to 131I in tumor accumulation. In the mouse model, the antitumor effects of the PEG and PIP linkers were almost the same. Most of the currently synthesized FAPI(s) contain PIP linkers; however, in our study, we found that PEG linkers exhibit equivalent performance. If the PIP linker is inconvenient, a PEG linker is expected to be an alternative.

Coordination between heart rate variability and physical activity may be diminished by fatigability in non-older women in the hour before sleep.

Fatigability is related to several diseases as well as the autonomic nervous system. We investigated whether fatigability is associated with coordination between physical acceleration (PA) and parasympathetic nervous activity (PSNA) in women. Overall, 95 women were divided into non-old (n = 50; age: 22-59 years) and old (n = 45; age: ≥60 years) groups. PSNA and PA data were simultaneously obtained every minute for 24 h. We defined %lag0 as the percent ratio of lag = 0 min between PSNA and PA in 1 h. Cornell Medical Index was used to determine the degrees of physical and psychological symptoms. In the non-older group in the hour before sleep, the participants with high fatigability scores had significantly lower %lag0 than those with low fatigability (p < 0.05). Additionally, those with higher fatigability combined with exhaustion in the morning had significantly lower %lag0 than those without exhaustion in the hour before sleep (p < 0.05) but not in the hour after waking up. These results suggest that fatigability in non-older women was associated with loss of coordination between PSNA and PA in the hour before sleep. Additionally, exhaustion in the morning may be related to loss coordination of PSNA and PA during the previous night.

Parasympathetic Nervous Activity Associated with Discoordination Between Physical Acceleration and Heart Rate Variability in Patients with Sleep Apnea.

Sleep apnea syndrome (SAS) often accompanies alterations in heart rate variability (HRV). The severity of SAS is sometimes evaluated using the oxygen desaturation index (ODI). We hypothesized that effects of the autonomic nervous system could be involved in the coordination between HRV and physical acceleration during free movement in patients with SAS. Among 33 women aged 60 years or older, 19 had a high ODI (>5). Their HRV and physical acceleration were simultaneously obtained every minute for 24 hours. The low frequency/high frequency (LF/HF) ratio and the high frequency in normalized units (HFnu) were used as HRV indices. Low levels of %Lag0, defined as the percentage of the lag = 0 min in 1 h, indicated coordination between physical acceleration and HRV. Nineteen participants were divided into group A (high %Lag0 before sleep [n = 9]) or group B (low %Lag0 [n = 10]). In group B participants with a high ODI and low %Lag0 in the hour after waking, HFnu was significantly increased compared to that in group A participants with high ODI and high %Lag0 in the hour after waking (p < 0.05). These results suggest that close associations between high ODI and discoordination between HRV and physical acceleration may be due to higher parasympathetic nervous system activity after waking.

Decrease in exhaled hydrogen as marker of congestive heart failure.

Objective: Hydrogen excretion is thought to be related to systemic antioxidation activity. H2 selectively reduces the hydroxyl radical of free hydrogen (·OH), a highly cytotoxic form of reactive oxygen species, in cultured cells. Methods: We investigated whether exhaled H2 decreased during night sleep, reflected ·OH production and was associated with heart failure severity. We enrolled 108 patients with chronic heart failure (CHF) and 15 control participants without CHF. H2 concentration was measured by gas chromatography in exhaled breath collected before sleep and in the morning after overnight fasting. Overnight change in H2 concentration (ΔH2) was calculated. Mitochondrial morphology evaluated by transmission electron microscopy in endomyocardial biopsies collected from 18 patients with dilated cardiomyopathy. Results: ΔH2 was significantly lower in patients with CHF compared with controls (-4.3±1.0 vs 2.0±2.1 ppm, p=0.030) and was positively correlated with cardiac index (CI; r = -0.285, p=0.003). Patients with a ΔH2<0 ppm had a significantly lower CI compared with those who had a ΔH2>0 ppm (2.85±0.61 vs 3.24±0.65 L/min/m2, p=0.005). ΔH2 was negatively correlated with both the percentage of vacuole-containing mitochondria and indices of cristae remodelling (r = -0.61, p=0.007). Conclusions: Decrease in exhaled H2 during night sleep was associated with CHF severity. ΔH2 warrants investigation as marker of CHF severity.

Exhaled Acetone Concentration Is Related to Hemodynamic Severity in Patients With Non-Ischemic Chronic Heart Failure.

BACKGROUND: We hypothesized that exhaled acetone concentration (EAC), reflecting altered blood ketone body metabolism and increased acetone exhaust because of pulmonary congestion in heart failure (HF), would correlate with hemodynamic parameters in patients with non-ischemic chronic HF. METHODS AND RESULTS: We prospectively enrolled 102 non-ischemic HF patients with New York Heart Association (NYHA) class I-III. Exhaled breath was collected after an overnight fast. Echocardiography and cardiac catheterization were performed in all patients. We also enrolled 17 control patients without HF. EAC in the HF patients was significantly higher than that in the control patients (median EAC; 0.53 vs. 0.38 ppm, P=0.012). EAC positively correlated with blood total ketone bodies (r=0.454, P<0.001), NYHA class (r=0.489, P<0.001), and plasma B-type natriuretic peptide (r=0.316, P=0.001). Right heart catheterization revealed that EAC significantly correlated with pulmonary capillary wedge pressure (PCWP, r=0.377, P<0.001). Receiver-operating characteristic analysis revealed that EAC >1.05 ppm was associated with PCWP ≥18 mmHg (area under the curve [AUC] 0.726, sensitivity 50%, specificity 89%). EAC was shown to be a comparable diagnostic biomarker for HF to BNP (AUC 0.760, sensitivity 80%, specificity 70%). CONCLUSIONS: EAC may be a novel noninvasive biomarker that correlates hemodynamic severity in non-ischemic chronic HF. (Circ J 2016; 80: 1178-1186).

The micro-flow reaction system featured the liquid-liquid interface created with ternary mixed carrier solvents in a capillary tube.

A micro-flow reaction system was developed in which liquid-liquid interface was created based on the tube radial distribution of ternary mixed carrier solvents. The system was constructed from double capillary tubes having different inner diameters (100 and 250 µm i.d.). The smaller tube was inserted into the larger one through a T-type joint. The reaction of a protein with a fluorescence derivatizing reagent was adopted as a model. A water-acetonitrile mixture (3:1 volume ratio) including bovine serum albumin (hydrophilic) was delivered into the large tube from the inside through the small tube and an acetonitrile-ethyl acetate mixture (7:4 volume ratio) containing fluorescamine (hydrophobic) as a derivatizing reagent was delivered from the outside through the joint. Solutions were mixed through the double capillary tubes to promote ternary mixed carrier solvents (water-acetonitrile-ethyl acetate; 1:2:1 volume ratio). The liquid-liquid interface was created based on the tube radial distribution of ternary solvents in the larger tube. The derivatization reaction was performed in the larger, or reaction, tube in the micro-flow system. The fluorescence intensity of the fluorescamine-derivatized bovine serum albumin obtained by the system, which specifically included the kinetic liquid-liquid interface in the tube, was greater than that obtained through a batch reaction using a homogeneous solution of water-acetonitrile (1:2 volume ratio).

Consideration of the tube radial distribution of the carrier solvents in a capillary tube under laminar flow conditions and computer simulation.

When the ternary mixed solvents of a water-hydrophilic/hydrophobic organic solvent mixture are delivered under microspace under laminar flow conditions, the solvent molecules are radially distributed in the microspace, and generate a major inner phase and a minor outer phase. We call this fluidic phenomenon as the tube radial distribution phenomenon (TRDP). In this paper, phase formation in the TRDP was collectively considered based on experimental data, such as the inner and outer phase formation in a microchannel under laminar flow conditions, the phase diagram for the ternary mixed solvents, the solvent-component ratios required for the TRDP, and the phase transformation in a batch vessel above atmospheric pressure, which were mainly reported in our previous papers. Furthermore, the formation of inner and outer phases in a capillary tube was simulated with the two-component solvents mixture model of water and ethyl acetate. Phase formations in capillary tubes were expressed through computer simulations.

Elution behavior of lambda-DNA with ternary mixed carrier solvents in an open-tubular capillary under laminar flow conditions.

An open-tubular capillary chromatography was developed based on the tube radial distribution of the ternary mixed carrier solvents that generated the inner and outer phases under laminar flow conditions. This is called "tube radial distribution chromatography" (TRDC). In this report, the elution behavior of lambda-DNA (48502 bp) as a biopolymer was examined by the TRDC system. The ternary mixture of water-acetonitrile-ethyl acetate, 15:3:2 or 3:8:4 volume ratio, as a carrier solution was fed into the capillary tube made of polytetrafluoroethylene (PTFE) or fused-silica. The mixture of hydrophobic 1-naphthol and hydrophilic lambda-DNA was subjected to the TRDC system using the water-rich carrier solution. Lambda-DNA and 1-naphthol were distributed between the inner and outer phases due to their hydrophilic and hydrophobic nature, and then eluted in this order, undergoing chromatographic separation. The mixture of hydrophilic 2,6-naphthalenedisulfonic acid and hydrophobic lambda-DNA that was treated with surfactants was also examined with the organic solvent-rich carrier solution. The modified hydrophobic DNA and 2,6-naphthalenedisulfonic acid were distributed and eluted in this order due to their nature.

Biomolecule analyses in an open-tubular capillary chromatography using ternary mixed carrier solvents with chemiluminescence detection.

We examined the elution behavior of isoluminol isothiocyanate (ILITC)-labeled biomolecules (α-amino acids, peptides, and proteins) in an open-tubular capillary chromatography system using an untreated fused-silica capillary tube and a water-acetonitrile-ethyl acetate mixture carrier solution. Such an open-tubular capillary chromatography is called "tube radial distribution chromatography (TRDC)" for convenience. A mixture of ILITC and ILITC-labeled biomolecules was analyzed using TRDC with chemiluminescence detection that provided simple instrument without a light source and complex optical devises. The ILITC and the labeled twenty α-amino acids were separated, in this order or the reverse order, or not separated with an organic solvent-rich and water-rich carrier solution. Their elution behavior was considered to be of hydrophilic or hydrophobic nature of ILITC and the labeled α-amino acids. The ILITC and the labeled protein, alcohol dehydrogenase and bovine serum albumin, were separated in this order with an organic solvent-rich carrier solution, while they were eluted in the reverse order with a water-rich carrier solution, based on the TRDC separation performance. The TRDC system worked with the untreated open-tubular capillary tube not using any specific capillary tubes, such as coated, packed, or monolithic.

Mixing process of ternary solvents prepared through microchannels in a microchip under laminar flow conditions.

The mixing process of ternary solvents (water-hydrophilic/hydrophobic organic mixture) prepared in microchannels in a microchip was examined by fluorescence observation of the dyes dissolved in the solvents under laminar flow conditions. A microchip incorporating microchannels was used. In it, three narrow channels were combined to form one wide channel. Water-acetonitrile (hydrophilic) mixture containing relatively hydrophilic Eosin Y (green) was fed into the narrow center channel and an acetonitrile-ethyl acetate (hydrophobic) mixture containing hydrophobic perylene (blue) was fed into the two narrow side channels in the microchip. The mixtures in the narrow channels combined in the wide channel to prepare the ternary solvents of water-acetonitrile-ethyl acetate, causing the tube radial distribution of the solvents. We observed the mixing process of the ternary solvents in the wide channel through fluorescence of the green and blue dyes, including an aqueous-organic interface. For example, the green dye that was fed into the center channel was distributed near the inner side walls and the blue dye that was fed into the two side channels was distributed around the center area in the wide channel. Such specific mixing behavior was not observed for two-component solvents in the wide channel, such as water-acetonitrile mixture and water-ethyl acetate mixture.

Tube radial distribution phenomenon of ternary mixed solvents in a microspace under laminar flow conditions.

When ternary mixed solutions of water-hydrophilic/hydrophobic organic solvents are fed into a microspace under laminar flow conditions, the solvent molecules are radially distributed in the microspace. The specific fluidic behavior of the solvents is termed "tube radial distribution phenomenon" (TRDP). In this study, water-acetonitrile-ethyl acetate mixed solutions (3:8:4 volume ratio) containing fluorescent dyes, perylene (0.1 mM) and Eosin Y (1 mM), were fed into fused-silica capillary tubes (75 µm i.d.) for investigating the TRDP with a fluorescence microscope-CCD camera under various analytical conditions. The pressure at the observation point for the fluorescence on the tube was changed by altering the flow rates, capillary total lengths, and capillary effective lengths. The obtained fluorescence images showed that the TRDP in the capillary tube created the inner and outer phases, i.e., the organic solvent-rich major inner and the water-rich minor outer phases in this case, providing the kinetic liquid-liquid interface. The formation of the inner and outer phases in the capillary tube was observed at flow rates of 0.5-2.0 µL min(-1) under the present analytical conditions. We also discuss the specific formation locations of the major and minor solvents.

Use of tube radial distribution of ternary mixed carrier solvents for introduction of absorption reagent for metal ion separation and online detection into capillary.

When ternary mixed solvents consisting of water-hydrophilic/hydrophobic organic solvents are fed into a micro-space under laminar flow conditions, the solvent molecules are radially distributed in the micro-space. The specific fluidic behavior of the solvents is called the "tube radial distribution phenomenon (TRDP)". A novel capillary chromatography method was developed based on the TRDP that creates the inner major and outer minor phases in a tube, where the outer phase acts as a pseudo-stationary phase. This is called "tube radial distribution chromatography (TRDC)". In this study, Chrome Azurol S as an absorption reagent was introduced into the TRDC system for metal ion separation and online detection. The fused-silica capillary tube (75 µm id and 110 cm length) and water-acetonitrile-ethyl acetate mixture (3:8:4 volume ratio) including 20 mM Chrome Azurol S as a carrier solution were used. Metal ions, i.e. Co(II), Cu(II), Ni(II), Al(III), and Fe(III), as models were injected into the present TRDC system. Characteristic individual absorption characteristics and elution times were obtained as the result of complex formation between the metal ions and Chrome Azurol S in the water-acetonitrile-ethyl acetate mixture solution. The elution times of the metal ions were examined based on their absorption behavior; Co(II), Ni(II), Al(III), Fe(III), and Cu(II) were eluted in this order over the elution times of 4.7-6.8 min. The elution orders were determined from the molar ratios of metal ion to Chrome Azurol S and Irving-Williams series for bivalent metal ions.

Experimental consideration of capillary chromatography based on tube radial distribution of ternary mixture carrier solvents under laminar flow conditions.

A capillary chromatography system has been developed based on the tube radial distribution of the carrier solvents using an open capillary tube and a water-acetonitrile-ethyl acetate mixture carrier solution. This tube radial distribution chromatography (TRDC) system works under laminar flow conditions. In this study, a phase diagram for the ternary mixture carrier solvents of water, acetonitrile, and ethyl acetate was constructed. The phase diagram that included a boundary curve between homogeneous and heterogeneous solutions was considered together with the component ratios of the solvents in the homogeneous carrier solutions required for the TRDC system. It was found that the TRDC system performed well with homogeneous solutions having component ratios of the solvents that were positioned near the homogeneous-heterogeneous solution boundary of the phase diagram. For preparing the carrier solutions of water-hydrophilic/hydrophobic organic solvents for the TRDC system, we used for the first time methanol, ethanol, 1,4-dioxane, and 1-propanol, instead of acetonitrile (hydrophilic organic solvent), as well as chloroform and 1-butanol, instead of ethyl acetate (hydrophobic organic solvent). The homogeneous ternary mixture carrier solutions were prepared near the homogeneous-heterogeneous solution boundary. Analyte mixtures of 2,6-naphthalenedisulfonic acid and 1-naphthol were separated with the TRDC system using these homogeneous ternary mixture carrier solutions. The pressure change in the capillary tube under laminar flow conditions might alter the carrier solution from homogeneous in the batch vessel to heterogeneous, thus affecting the tube radial distribution of the solvents in the capillary tube.

Fluorescence observation supporting capillary chromatography based on tube radial distribution of carrier solvents under laminar flow conditions.

We developed a capillary chromatography system by using an open capillary tube made of fused-silica, polyethylene, or polytetrafluoroethylene, and a water-hydrophilic/hydrophobic organic mixture carrier solution, called tube radial distribution chromatography (TRDC) system. By comparing with chromatograms obtained via the TRDC system, fluorescence photographs and profiles of the fluorescent dyes dissolved in the carrier solvents in capillary tubes were observed under laminar flow conditions. The chromatograms were obtained for a model mixture analyte consisting of 1-naphthol and 2,6-naphthalenedisulfonic acid with the TRDC system, by using a fused-silica capillary tube and a water-acetonitrile-ethyl acetate carrier solution. By altering the carrier flow rates, we examined the fluorescence photographs and profiles of the dyes, perylene and Eosin Y, dissolved in the carrier solvents in the capillary tube by using a fluorescence microscope equipped with a CCD camera. As confirmed by fluorescence observations, the major inner and minor outer phases generated in the capillary tube were based on the tube's radial distribution of the carrier solvents. We designed and manufactured a microreactor incorporating microchannels in which three narrow channels combined to form one wide channel. When the carrier solvents containing the dyes were fed into the channels, the inner and outer phase generations were also observed in the narrow and wide channels, strongly supporting the conclusions concerning the tube radial distribution phenomenon of the solvents.

Analytical conditions and separation performance of capillary chromatography based on the tube radial distribution of aqueous-organic mixture carrier solvents under laminar-flow conditions.

We have developed a capillary chromatography system using an open capillary tube made of fused-silica, polyethylene, or poly(tetrafluoroethylene), and a water-hydrophilic-hydrophobic organic mixture carrier solution. This tube radial distribution chromatography (TRDC) system works under laminar-flow conditions. In this study, the following analytical conditions in the TRDC system using a fused-silica capillary tube and a water-acetonitrile-ethyl acetate mixture carrier solution were for the first time examined: tube temperature, 5-25 degrees C; tube inner diameter, 50-250 microm; tube effective length, 100-200 cm; and flow rate, 0.2-1.5 microL min(-1). For example, the effects of temperature on the separation performance in the TRDC system were observed with an organic solvent-rich carrier solution; 1-naphthol and 2,6-naphthalenedisulfonic acid in a model mixture were eluted with baseline separation over the temperature range of 5-23 degrees C. The resolution, theoretical plate number, and height equivalent to the theoretical plate were calculated from the experimental data obtained by examining the effects of the tube length. A mixture of 1-naphthol, Eosin Y, 1-naphthalenesulfonic acid, 2,6-naphthalenedisulfonic acid, and 1,3,6-naphthalenetrisulfonic acid was subjected to the present TRDC system, and the analytes in the mixture solution were eluted in this order with the organic solvent-rich carrier solution, providing good separation performance on the chromatogram.

Separation of optical isomers in capillary chromatography using a poly(tetrafluoroethylene) capillary tube and an aqueous-organic mixture carrier solution.

Capillary chromatography for the separation of optical isomers was developed using an untreated poly(tetrafluoroethylene) capillary tube and a water-hydrophilic/hydrophobic organic solvent mixture as a carrier solution. The open tubular capillary was 110 cm in length (90 cm effective length) and 100 microm in inner diameter. The carrier solution was prepared with a water-acetonitrile-ethyl acetate mixture (15:3:2 volume ratio) containing 1 mM beta-cyclodextrin. A model analyte solution of dansyl-DL-methionine was injected into the capillary tube by a gravity method. The analyte solution was subsequently delivered through the capillary tube with the carrier solution by a microsyringe pump; the system worked under laminar-flow conditions. The analytes were separated through the capillary tube with on-capillary detection by an absorption detector. D-Isomer and L-isomer were eluted in this order with the water-acetonitrile-ethyl acetate carrier solution including beta-cyclodextrin.

Capillary chromatography based on tube radial distribution of aqueous-organic mixture carrier solvents: introduction of double tubes having different inner diameters to the system.

A tube radial distribution chromatography (TRDC) system was previously developed using an open capillary tube and an aqueous-organic solvent (water-acetonitrile-ethyl acetate) mixture as a carrier solution. In this study, we introduced double capillary tubes having different inner diameters to the system. The tubes were fused-silica capillary tubes with 100 and 250 microm i.d.; the smaller tube was inserted into the larger one through a T-type joint. Water-acetonitrile mixture (volume ratio 3:1) and acetonitrile-ethyl acetate mixture (volume ratio 4:1) solutions were delivered into the large tube from the inside through the small tube and from the outside through the joint, respectively, and then mixed through the large tube to provide a water-acetonitrile-ethyl acetate carrier solution. The carrier solution was further fed into the large tube and then to an absorption detector. By changing the flow rates of the mixture solutions in both tubes, we could control the component ratio of carrier solvents in the carrier solution, yielding either organic solvent-rich, water-acetonitrile-ethyl acetate (volume ratio 3:33:8) or water-rich, water-acetonitrile-ethyl acetate (volume ratio 24:12:1). A model analyte-mixture solution of 1-naphthol and 2,6-naphthalenedisulfonic acid was eluted in this order with the organic solvent-rich carrier solution and eluted in the reverse order with the water-rich carrier solution. We discussed the chromatographic data together with the analytical conditions from the viewpoint of the tube radial distribution of the carrier solvents.

Capillary chromatography based on tube radial distribution of aqueous-organic mixture carrier solvents: Introduction of inner-wall-modified capillary tubes.

We developed a novel capillary chromatography using an open capillary tube and a water-hydrophilic/hydrophobic organic solvent mixture as a carrier solution. The capillary chromatography was called a tube radial distribution chromatography (TRDC) system. In this study we tried to introduce inner-wall-modified (e.g. phenylboronic-acid- and iminodiacetic-acid-modified) fused-silica capillary tubes to the TRDC system to separate model mixture analytes. The phenylboronic-acid-modified capillary tube was combined with absorption detection to analyze a mixture of adenosine and deoxyadenosine. The iminodiacetic-acid-modified capillary tube was combined with chemiluminescence detection using a luminol reaction to analyze a mixture of copper(II) and hematin. A water (carbonate buffer)/ACN/ethyl acetate (2:7:4 v/v/v) and a water (carbonate buffer)/ACN/ethyl acetate (15:3:2 v/v/v) mixture solution were used as carrier solutions in the TRDC system, and typical carbonate buffer solutions not containing any organic solvents were also used as carrier solutions as reference solutions. In both modified capillary tubes, the organic-solvent-rich carrier solution successfully improved the separation of the mixture analytes in the system, and the water-rich carrier solution greatly depressed their separation, when compared with chromatography using carbonate buffer carrier solutions containing no organic solvents. Such observed phenomena were discussed considering the separation mechanism of the TRDC system.