Structural and diffusion properties of formamide/water mixture interacting with TiO2 surface.

The photoreaction and adsorption properties on surfaces, thermal decomposition, chemical transformation, and other properties of the formamide molecule are widely used to understand the origins of the formation of biological molecules (nucleosides, amino acids, DNA, monolayers, etc.) needed for life. The titanium oxide (TiO2) surface can act both as a template on which the accumulation of adsorbed molecules like formamide occurs through the concentration effect, and as a catalytic material that lowers the activation energy needed for the formation of intermediate products. In this paper, a formamide-water solution interacting with TiO2 (anatase) surface is simulated using the molecular dynamics method. The structural, diffusion and density properties of formamide-water mixture on TiO2 are established for a wide temperature range from T=250 K up to T=400 K.

Activation Energy Calculations for Formamide-TiO2 and Formamide-Pt Interactions in the Presence of Water.

Formamide contains the four elements (C, H, O, and N) most required for life and it is attractive as a potential prebiotic starting material for nucleobase synthesis. In the presence of catalysts (for example, TiO2) and with moderate heating, formamide can pass surface energy barriers, yielding a complete set of nucleic bases and acyclonucleosides, and favoring both phosphorylations and transphosphorylations necessary for life. In the reaction mechanism, interaction with water seems to be an essential factor for the formamide molecule to function. In this paper, a formamide-water solution on a TiO$_2$ (anatase) surface is simulated using the molecular dynamics method, and activation energy calculations are performed for the temperature range of T = 250 K to T = 400 K. A correlation is established between the diffusion and density profiles for the formamide and water molecules on an anatase surface. Also, the calculated activation energies of the formamide-water-anatase and formamide-water-platinum systems are compared. A comparative analysis is performed of the behavior of formamide-water and ethanol-water interaction on the same (anatase and platinum) surfaces.

Novel antagonists for proteinase-activated receptor 2: inhibition of cellular and vascular responses in vitro and in vivo.

BACKGROUND AND PURPOSE: Proteinase-activated receptor 2 (PAR(2)) is a G-protein coupled receptor associated with many pathophysiological functions. To date, the development of PAR(2) antagonists has been limited. Here, we identify a number of novel peptide-mimetic PAR(2) antagonists and demonstrate inhibitory effects on PAR(2)-mediated intracellular signalling pathways and vascular responses. EXPERIMENTAL APPROACH: The peptide-mimetic compound library based on the structures of PAR(2) agonist peptides were screened for inhibition of PAR(2)-induced calcium mobilisation in human keratinocytes. Representative compounds were further evaluated by radioligand binding and inhibition of NFkappaB transcriptional activity and IL-8 production. The vascular effects of the antagonists were assessed using in vitro and in vivo models. KEY RESULTS: Two compounds, K-12940 and K-14585, significantly reduced SLIGKV-induced Ca(2+) mobilisation in primary human keratinocytes. Both K-12940 and K-14585 exhibited competitive inhibition for the binding of a high-affinity radiolabelled PAR(2)-ligand, [(3)H]-2-furoyl-LIGRL-NH(2), to human PAR(2) with K(i) values of 1.94 and 0.627 microM respectively. NFkappaB reporter activity and IL-8 production were also significantly reduced. Furthermore, relaxation of rat-isolated aorta induced by SLIGRL-NH(2) was inhibited competitively by K-14585. K-14585 also significantly lowered plasma extravasation in the dorsal skin of guinea pigs and reduced salivation in mice. CONCLUSIONS AND IMPLICATIONS: K-12940 and K-14585 antagonized PAR(2) competitively, resulting in inhibition of PAR(2)-mediated signalling and physiological responses both in vitro and in vivo. These peptide-mimetic PAR(2) antagonists could be useful in evaluating PAR(2)-mediated biological events and might lead to a new generation of therapeutically useful antagonists.

Wall motion velocities of abdominal aorta measured by tissue Doppler imaging in normal children.

Tissue Doppler imaging (TDI) offers a new technique for assessing aortic wall expansion/contraction velocities and may provide a noninvasive approach to aortic wall mechanics. The purpose of this study was to determine the normal values of abdominal aortic wall motion velocities and the effect of age on these velocities in normal children. We examined 103 normal children. Using TDI, maximum wall expansion velocity during systole (peak S) and maximum wall contraction velocity during diastole (peak D) were measured. M-mode diameter of the abdominal aorta and systolic, diastolic, and mean arterial pressures were measured. Aortic stiffness was measured as (I(n)[BP(syst)/BP(diast)])/(D(s)-D(d)/D(d), where I(n) is the natural log, D(s) is the maximal abdominal aortic diameter during systole, and D(d) is the abdominal aortic diameter at end-diastole. In all subjects, wall motion velocities of the abdominal aorta were recorded. The mean values for peak S and peak D were 4.23, 1.14 and 2.16, 0.45 cm/sec, respectively. Both peak S and peak D were low in infants and increased significantly with age (r = 0.63, p < 0.0001 and r = 0.36, p = 0.0002, respectively), systolic blood pressure (r = 0.42 and 0.47, respectively, p < 0.0001), and diastolic blood pressure (r = 0.24, p = 0.016 and r = 0.28, p = 0.0038, respectively). Aortic stiffness index of the abdominal aorta was constant with age and did not correlate with peak S or peak D. Abdominal aortic wall motion velocities can be easily assessed by TDI. Age-related changes in the aortic wall motion velocities are observed in normal children. This study provides baseline information for further quantitative assessment of arterial stiffness in children with congenital or acquired heart disease.

Nanoscale hydrophobic interaction and nanobubble nucleation.

We report large-scale atomistic simulation of midrange nanoscale hydrophobic interaction, manifested by the nucleation of nanobubble between nanometer-sized hydrophobes at constrained equilibrium. When the length scale of the hydrophobes is greater than 2 nm, the nanobubble formation shows hysteresis behavior resembling the first-order transition. Calculation of the potential of mean force versus interhydrophobe distance provides a quantitative measure of the strength of the nanoscale hydrophobic interaction.

Tei index determined by tissue Doppler imaging in patients with pulmonary regurgitation after repair of tetralogy of Fallot.

The myocardial performance index (Tei index) determined by the pulsed Doppler method is a simple and noninvasive measurement for assessing global right ventricular (RV) function. This index can also be obtained by tissue Doppler imaging (TDI). The effects of significant pulmonary regurgitation (PR) on the determination of the Tei index by these two methods have not been investigated. We examined 15 patients (6.3 +/- 2.2 years) with significant PR after repair of tetralogy of Fallot (TOF) and 24 age-matched healthy children. Myocardial wall motion velocities at the tricuspid annulus were assessed during systole (Sa), early diastole (Ea), and late diastole (Aa) from a four-chamber view. Pulsed Doppler-Tei index and TDI-Tei index were measured as reported previously. The Tei index obtained by the pulsed Doppler method in TOF patients did not differ from that in normal children (0.30 +/- 0. 12 vs 0.32 +/- 0.07, p = not significant). TDI showed that TOF patients had significantly decreased Ea, Aa, and Sa velocities compared to those of normal children. Both isovolumic contraction time and isovolumic relaxation time in TOF patients were significantly longer than those in normal children (88 +/- 18 vs 62 +/- 23 msec and 46 +/- 11 vs 21 +/- 12 msec, respectively; p < 0.0001), although the duration of Sa did not differ between the two groups. Consequently, the Tei index as measured by TDI was significantly greater in TOF patients than in normal children (0.48 +/- 0.07 vs 0.30 +/- 0.07, p < 0.0001). The Tei index measured by the pulsed Doppler method is limited in its ability to assess RV function in patients with significant PR. However, the Tei index determined by TDI is a sensitive indicator of RV function in these patients, and it appears to be a promising new means of assessing global RV function in patients with significant PR.

Effect of dobutamine on a Doppler echocardiographic index of combined systolic and diastolic performance.

Dobutamine stress echocardiography has become accepted in the evaluation of cardiac functional reserve. Although the Doppler-derived index of combined systolic/diastolic myocardial performance (Tei index) has been reported to be easily obtainable and useful for predicting left ventricular performance, the effect of dobutamine on the Tei index has not been determined in children. To assess the effect of dobutamine on the Tei index, 8 patients who had undergone surgery for ventricular septal defect and 7 patients who had a history of Kawasaki disease were examined. Echocardiographic recordings were obtained before and after dobutamine infusion (5 microg/kg per minute). Variables measured were transmitral flow velocities (E, A, E/A), rate-corrected mean velocity of circumferential fiber shortening (rate-corrected Vcf), and IMP. We measured isovolumic contraction time (ICT), isovolumic relaxation time (IRT), and ejection time (ET) and then calculated the Tei index using the following formula: Tei index = (ICT + IRT)/ET. Dobutamine infusion increased rate-corrected Vcf (29%, p < 0.01), peak E (7%, p < 0.05), and peak A (13%, p < 0.05). E/A ratio did not change during dobutamine infusion. ET, ICT, and IRT were found to decrease during dobutamine infusion. The magnitude of the change in the ICT (-21%, p < 0.01) was greater than those in IRT (-12%, p < 0.01) and ET (-8%, p < 0.05). The decrease in Tei index (-16%, p < 0.01) resulted in a decrease in ICT/ET (-21%, p < 0.01) and a slight decrease in IRT/ET (-12%, p < 0.05). The Tei index has potential as a sensitive indicator of the effects of inotropic stimilation on global left ventricular function.

[Public music concerts in a psychiatric hospital: effects on public opinion and as therapy for patients].

We investigate the effects of music therapy concerts, which were held 60 times over a four year period, 1992 to 1996, in Geiyo Psychiatric Hospital, Kochi Prefecture and found that; 1) Musicians who performed at the concerts were not only from Kochi prefecture but also from other prefectures (10 times) and from four foreign countries (7 times). 2) Live concerts in a small hall had a positive influence on patients and drew the patient's attention and interest away from their hallucinations and delusions to the real world. Moreover, the concerts provided the patients with chances to acquire social graces such as being well-groomed. 3) Explanations by the musicians, interviews with the musicians and the seasonal choruses accompanied by the musicians were helpful to give the patients motives for recovering communication skills and to interact with society. 4) Inquiries to the patients about the concerts indicated discrepancies between the poor observed estimations during the concerts (83.3%) and the good subjective impressions expressed by the patients (82.0%), suggesting that the patients were not good at expressing their internal emotions through facial expressions or attitudes. 5) Many citizens including children came to the concerts and/or gave aid to the hospital because the concerts were open to the public and we suggest that this contributed to improving the general publics' image of psychiatric hospitals. Questionnaires revealed that 90% of people in a control group had a bad image of psychiatric hospitals in Japan, but only 32% of the members of the general public who attended our concerts had a bad image of psychiatric hospitals. In addition, the revolving ratio of the hospital beds rose from 0.4 to 1.2 over the four years, which also suggests a beneficial effect on the patients.

A comparison of tissue Doppler imaging and velocities of transmitral flow in children with elevated left ventricular preload.

Compared with transmitral velocities of flow, myocardial wall velocities obtained by tissue Doppler imaging are less influenced by left atrial pressure. The data supporting this assumption, however, are limited in patients with congenital cardiac disease. The aim of this study was to compare the effects of left ventricular preload on transmitral inflow and velocities assessed by tissue Doppler imaging. Tissue Doppler imaging, and conventional Doppler echocardiography with simultaneous invasive hemodynamic studies, were performed in 33 patients with a simple ventricular septal defect or patency of the arterial duct. Transmitral velocities (E, A) and mitral annular velocities (Ea, Aa) were measured, permitting calculation of the ratio of E to Ea. The ratio of pulmonary to systemic flows, and mean left atrial pressure, were also measured. In 10 of 33 patients, echocardiographic and hemodynamic studies were performed 4 to 5 months after surgery. The E and A values in the patients were greater than those in the controls (p < 0.01). In contrast, neither Ea nor Aa differed between the two group. The ratio of E to Ea in the patients increased significantly compared with that in the controls (8.9+/-2.1 vs 7.3+/-1.3, p < 0.01). The E value was directly related to mean left atrial pressure and the ratio of pulmonary to systemic flows. The velocities measured by Tissue Doppler imaging, however, had no significant relationship to either of these measurements. The ratio of E to Ea correlated well with mean left atrial pressure (r = 0.75, p < 0.01). In 10 post-operative patients, the values for E and A decreased from 119+/-14 to 89+/-10 cm/sec (p < 0.01) and from 91+/-22 to 61+/-9 cm/sec (p < 0.01), respectively. No significant changes were noted in the values of Ea and Aa. The ratio of E to Ea, and mean left atrial pressure, decreased from 10.3+/-1.9 to 8.2+/-1.5 (p < 0.01) and from 11.0+/-1.8 to 7.4+/-1.0 mmHg (p < 0.01), respectively. The percentage change in left atrial pressure correlated with the percent change in the ratio of E to Ea (r = 0.64, p < 0.05). The present study showed that the velocities obtained with tissue Doppler imaging are less dependent on mean left atrial pressure in children with elevated left ventricular preload caused by a left-to-right shunt.

Coronary blood flow assessed by transthoracic echocardiography in neonates.

Coronary flow measurement has provided useful clinical and physiologic information. However, there is little information about values for coronary flow in normal neonates, much less neonates with congenital heart disease. The aim of this study was to assess coronary blood flow in normal neonates and to compare the results with those in infants with ventricular septal defect. The study groups consisted of 12 normal neonates and 9 infants with simple ventricular septal defect associated with pulmonary hypertension. Left ventricular dimension, left ventricular mass, and the diameter of the coronary vessel were measured by standard M-mode and two-dimensional echocardiography. Peak flow velocities, flow velocity integrals, and flow volumes in the left anterior descending and circumflex coronary arteries were measured. The flow signals from the left anterior descending and circumflex coronary arteries were recorded in 84% (10/12) and 17% (2/12), respectively, in the normal neonates and 78% (7/9) and 11% (1/9), respectively, in the patients. The left ventricular end diastolic diameter and mass were significantly lower in normal infants than in the infants with ventricular septal defect (1.56 +/- 0.11 vs 1.84 +/- 0.09 cm and 5.4 +/- 1.6 vs 8.8 +/- 0.8 g, respectively, p < 0.01). The mean peak diastolic velocity and the flow velocity time integral in the left anterior descending coronary artery were significantly lower in the normal neonates than in the patients (15 +/- 4 vs 28 +/- 6 cm/sec and 2.3 +/- 0.6 vs 5.9 +/- 1.5 cm, respectively, p < 0.01). The coronary flow volume was significantly lower in the normal neonates than in the patients (3.1 +/- 1.4 vs 7.9 +/- 4.7 ml/min, p < 0.05). However, the flow volume of the left anterior descending coronary artery/left ventricular mass did not show any significant difference between the two groups. Our study demonstrated in neonates that it is feasible to detect noninvasively and to evaluate the flow of the left anterior descending coronary artery under physiologic conditions and abnormal hemodynamic situations. Increased flow volume in the left anterior descending coronary artery in patients with ventricular septal defect may be a compensated mechanism for the increase in oxygen demand of hypertrophic myocardium of the left ventricle.

Effects of dobutamine on coronary flow velocity response and their relations to age.

The purpose of this study was to assess the effects of low-dose dobutamine on left ventricular (LV) functional and coronary flow reserves using transthracic echocardiography. The study group consisted of 30 children aged from 5 months to 16 years (mean 4.8 +/- 4.4 years). Echocardiographic studies were repeated before and during dobutamine infusion (5 microg/kg per minute). The peak diastolic velocity in the left descending coronary artery (LAD) was recorded by pulsed-Doppler under the guidance of color Doppler flow mapping. The coronary flow velocity (CFV) response was calculated as the ratio of LAD peak flow velocity at dobutamine infusion to basal LAD peak flow velocity. Left ventricular contractility was calculated by two-dimensionally directed M-mode echocardiography. The rate-corrected mean velocity of circumferential fiber shortening (mVcfc) and LV end-systolic wall stress (ESS) were used as indices of contractility. Adequate spectral Doppler recordings of the LAD peak flow velocity for the assessment of CFV response were obtained in 26 of 30 patients (87%). The LAD peak flow velocity at dobutamine infusion increased significantly compared with the basal values. The CFV response in the younger children was low and increased significantly with age. The CFV response did not show significant correlations with the changes in heart rate, systolic blood pressure, rate-pressure product, nor ESS during dobutamine infusion. However, a significant relationship between the CFV response and the percent change of mVcfc was observed. In the present study using high frequency transthoracic echocardiography, we demonstrated the age-related changes in CFV response and LV functional reserve by dobutamine infusion. Responses of LV contractility and coronary flow to dobutamine are less sensitive in youngerchildren and increased with increasing age.

Tissue doppler imaging of left and right ventricles in normal children.

Tissue Doppler imaging is a new ultrasound technology that derives measurements of contraction and relaxation velocities directly from the myocardium. However, data on myocardial velocities by using tissue Doppler imaging have not been established in normal children. In 48 normal children, myocardial velocities were measured using tissue Doppler imaging at three different sites (base, middle, and apex) in the left and right ventricles and the interventricular septum. In the left ventricular wall, the peak myocardial velocities during early diastole (peak E), during atrial contraction (peak A), and during systole (peak S) waves decreased gradually between the base and apical sites, whereas the ratio of E to A waves (peak E/A wave ratio) did not change among the 3 segments. Similar findings were obtained from the myocardial velocities in the right ventricle and the interventricular septum. A systolic and diastolic velocity gradient was also observed between the different ventricular walls. Significant correlations of the tissue Doppler parameters with age or heart rate were observed. In the left ventricle, the peak E wave demonstrated a stronger relation with age (r=0.77) than with heart rate (r=-0.65). The peak A wave did not change with age but correlated with heart rate. The peak E/A wave ratio showed a weaker relation with age (r=0.54) than with heart rate (r=0.62). The peak S wave was related to age (r=0.65) and to a lesser extent to heart rate (r= -0.51). Similar relationships of tissue Doppler parameters with age or heart rate were observed for the right ventricle and interventricular septum. The heterogeneous pattern and age- and heart-rate-related changes in normal myocardium demonstrated in this study must be taken into account when attempting to identify altered regional myocardial function with tissue Doppler echocardiography.

Intracellular behavior of rabies virus matrix protein (M) is determined by the viral glycoprotein (G).

To investigate the nature and intracellular behavior of the matrix (M) protein of an avirulent strain (HEP-Flury) of rabies virus, we cloned and sequenced the cDNA of the protein. Using expression vectors pZIP-NeoSV(X)1 and pCDM8, the cDNA was transfected to animal cells (BHK-21 and COS-7) with or without coexpression of viral glycoprotein (G). When M protein alone was expressed in the cells, it displayed homogeneous distribution in the whole cell including the nucleus. In contrast, coexpression with G protein resulted in the abolishment of nuclear distribution of M antigen, and both of the antigens displayed a colocalized distribution in the cell, especially at the cellular membrane as seen in the virus-infected cells, while the distribution of G antigen was not affected by coexpressed M antigen. Immunoprecipitation studies revealed that M protein was coprecipitated with G protein by anti-G antibody, and vice versa, although cross-linking with dithiobis(succinimidyl propionate) was necessary for coprecipitation because of their easier dissociation in the presence of sodium deoxycholate. These results suggest that M protein intimately associates with G protein, which may affect or regulate the behavior (e.g., intracellular localization) of M protein. Studies with deletion mutants of M protein indicate that an internal region around the amino acids from 115 to 151 is essential for the M protein to preserve its binding ability to G protein.

Right ventricular diastolic filling assessed by conventional doppler and tissue Doppler imaging in normal children.

To examine age-related changes in right ventricular filling dynamics, we performed conventional pulsed Doppler (n=99) and tissue Doppler (n=30) echocardiographic studies in normal subjects aged 7 days to 273 months. The tricuspid flow velocity during early diastole (peak E) wave correlated significantly but weakly with the logarithm of age. The peak E wave in the early neonatal period was almost 80% of the older children's values and increased to 100% by 36 months of age. In the right ventricular tissue Doppler imaging, the peak myocardial velocity during early diastole also increased significantly with the logarithm of age. However, the tissue Doppler peak A did not change with age. There was a significant correlation between the tissue Doppler peak E wave and the tricuspid peak E wave and between the tissue Doppler peak E/A wave and the tricuspid peak E/A wave. The age-related changes in the tricuspid inflow velocity patterns were similar to the age-related alterations in the right ventricular myocardial velocity patterns. Age-related changes in the tricuspid inflow velocity and myocardial velocity patterns may be related to age-related maturation in the right ventricular diastolic performance.

Bioprocess fault detection by nonlinear multivariate analysis: application of an artificial autoassociative neural network and wavelet filter bank.

A nonlinear multivariate analysis, artificial autoassociative neural network (AANN), was applied to bioprocess fault detection. In an optimal production process of a recombinant yeast with a temperature controllable expression system, faults in test cases with faulty temperature sensors and plasmid instability of recombinant cells could be detected by the AANN. Since the raw data of measured variables included high-frequency noise, a wavelet filter bank (WFB) was applied to noise elimination before training of the AANN. The filtering performance of the WFB was compared with those of some classical first-order digital filters. The filtered signals at several resolution scales by the WFB were employed as the training data of the AANN. The computing time and summation of square of errors in training were compared, and the appropriate degree of the noise filtering and the density of the training data of the AANN were discussed. The performance of the feature capturing by the AANN was compared with that by a linear multivariate analysis, principal component analysis. A J index defined in this paper, using inputs and outputs of the AANN, was used for fault detection successfully. The output of the first unit of the trained AANN functioned effectively for the discrimination of the data in the abnormal cases from the data in the normal cases.

Management and design of the maintenance of SAM mouse strains: an animal model for accelerated senescence and age-associated disorders.

The Senescence-Accelerated Mouse (SAM) was established by inbreeding and pedigree selection based on the life span, degree of senescence, as well as the incidence and degree of several age-associated disorders. At first, SAM strains were developed under conventional conditions, but now some strains are also maintained under specific pathogen-free conditions. There are many methods used to maintain such strains of mice; our methods will be introduced as one example of how to develop and maintain strains of mice used in aging research.

Acceleration of chromosome aberrations in senescence-accelerated strains of mice.

Age-related changes in the frequency of chromosome aberrations were examined using bone marrow cells of senescence-accelerated strains of mice (SAM). An accelerated senescence-prone strain, SAM-P/1, showed a striking increase in the frequency of chromosome aberrations, from age 3 to 8 months, whereas an accelerated senescence-resistant strain, SAM-R/1, at the same ages showed only a slight increase. Both these strains were derived from the same ancestral strain (AKR/J). The rate of increase of chromosome aberration frequency paralleled the advancement of senescence in both strains. These observations suggest that there are genetic factors which closely relate to chromosomal instability and acceleration of the senescence processes.

Interaction of adenosine-5'-O-(3-thiotriphosphate) with Ca2+,Mg2+-adenosine triphosphatase of sarcoplasmic reticulum.

Interaction of adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S) with Ca2+,Mg2+-ATPase of sarcoplasmic reticulum was studied. The nucleotide was slowly hydrolyzed by the ATPase at 30 degrees C at a rate of about 0.5% that of ATP hydrolysis. Whereas at 0 degrees C, ATP gamma S showed only a limited reactivity toward the ATPase in that a thiophosphorylated intermediate was formed and ADP was released, but hydrolysis of the intermediate to complete the catalytic cycle did not occur. A fairly stable analog of the E-P intermediate could thus be obtained. Presence of the thiophosphorylated intermediate was indicated by the [3H]ADP in equilibrium ATP gamma S exchange reaction and also by using [35S]ATP gamma S. When the ATPase was reacted with ATP gamma S at 0 degrees C in the presence of ferricyanide, EP-forming activity was rapidly lost. Free Ca2+ ions were required for this inactivation. Disulfide bond formation between a cysteinyl residue located near the substrate binding site and the enzyme-bound ATP gamma S or the thiophosphorylated intermediate was suggested by the fact that 2-mercaptoethanol reversed the inactivation. The reaction may prove to be a useful tool for affinity labeling of the active site of the ATPase.