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PubMed2005

Derivation of a quantitative minimal model from a detailed elementary-step mechanism supported by mathematical coupling analysis.

Accurate experimental data increasingly allow the development of detailed elementary-step mechanisms for complex chemical and biochemical reaction systems. Model reduction techniques are widely applied to obtain representations in lower-dimensional phase space which are more suitable for mathematical analysis, efficient numerical simulation, and model-based control tasks. Here, we exploit a recently implemented numerical algorithm for error-controlled computation of the minimum dimension required for a still accurate reduced mechanism based on automatic time scale decomposition and relaxation of fast modes. We determine species contributions to the active (slow) dynamical modes of the reaction system and exploit this information in combination with quasi-steady-state and partial-equilibrium approximations for explicit model reduction of a novel detailed chemical mechanism for the Ru-catalyzed light-sensitive Belousov-Zhabotinsky reaction. The existence of a minimum dimension of seven is demonstrated to be mandatory for the reduced model to show good quantitative consistency with the full model in numerical simulations. We derive such a maximally reduced seven-variable model from the detailed elementary-step mechanism and demonstrate that it reproduces quantitatively accurately the dynamical features of the full model within a given accuracy tolerance.

Journal Article↗
PubMed2007

Artifact reduction in moving-table acquisitions using parallel imaging and multiple averages.

Two-dimensional (2D) axial continuously-moving-table imaging has to deal with artifacts due to gradient nonlinearity and breathing motion, and has to provide the highest scan efficiency. Parallel imaging techniques (e.g., generalized autocalibrating partially parallel acquisition GRAPPA)) are used to reduce such artifacts and avoid ghosting artifacts. The latter occur in T(2)-weighted multi-spin-echo (SE) acquisitions that omit an additional excitation prior to imaging scans for presaturation purposes. Multiple images are reconstructed from subdivisions of a fully sampled k-space data set, each of which is acquired in a single SE train. These images are then averaged. GRAPPA coil weights are estimated without additional measurements. Compared to conventional image reconstruction, inconsistencies between different subsets of k-space induce less artifacts when each k-space part is reconstructed separately and the multiple images are averaged afterwards. These inconsistencies may lead to inaccurate GRAPPA coil weights using the proposed intrinsic GRAPPA calibration. It is shown that aliasing artifacts in single images are canceled out after averaging. Phantom and in vivo studies demonstrate the benefit of the proposed reconstruction scheme for free-breathing axial continuously-moving-table imaging using fast multi-SE sequences.

Artifacts↗
PubMed2004

Aberration reduction by multiple relays of an incoherent image.

Consider a generally aberrated one-dimensional (1D) optical pupil P illuminated by quasi-monochromatic light of mean wavelength lambda. In past work it was found that, if the pupil's intensity point-spread function (psf) is multiply convolved with itself, as in an imaging relay system, and then ideally (stigmatically) demagnified, the resulting psf s(x) approaches a fixed Cauchy form s(x) = deltax( pi2x2 + deltax2)(-1), which is independent of the aberrations of the pupil. Here deltax is the Nyquist sampling interval given by deltax = lambdaf/2 with f the f/number of the pupil. This Cauchy form for this intensity psf s(x) also manifestly lacks sidelobes. The overall questions that we examine are how far do these effects carry over to the case of a circular, two-dimensional (2D) pupil, and to what extent do practical imaging considerations compromise the theoretical results? It is found that, in the presence of spherical aberration of all orders, the resulting theoretical psf of a large number of self-convolutions approaches a "circular" Cauchy form, S(r) = 2deltar[pi2r2 + (4deltar/pi)2](-3/2), where deltar is the Nyquist sampling interval lambdaf/2 with f the f/number of the (now) circular pupil. Thus, for these aberrations the 1D effect does carry over to the 2D case: The output psf does not depend on the aberrations and completely lacks sidelobes. However, when all aberrations are generally present, the output psf s(r, theta) does depend on the aberrations, although its azimuthal average over theta still preserves the circular Cauchy form, as a superposition of Cauchy functions. Imaging requirements for achieving these ideal effects are briefly discussed as well as probability laws for photons that are implied by the above-mentioned PSF's s(x) and S(r). Real-time super resolution is not attained, since the stigmatic imaging demanded of the demagnification step requires the use of a larger-apertured lens. Rather, the approach achieves significant aberration suppression.

Journal Article↗
PubMed2004

[Usefulness of 3D conformal radiation therapy for reduction of radiation-induced white matter injury].

PURPOSE: The usefulness of three-dimensional conformal radiation therapy(3DCRT) in decreasing radiation-induced white matter changes(WMC) was assessed. MATERIAL AND METHODS: Thirty-seven patients(age 5-77 years, mean 42 years; male/female = 11/26) with primary intracranial tumors received 40 Gy or more, and were followed up with MRI for more than one year. Thirty-four patients underwent chemotherapy(with a platinum drug, 16; without a platinum drug, 18). Nineteen were treated with 3DCRT (radiation dose, range 60-64 Gy, mean 60.2 Gy; maximum width of radiation field, range 7-16 cm, mean 12.5 cm) and 18 were treated with non-3DCRT (radiation dose, range 40-62.4 Gy, mean 53.4 Gy; maximum width of radiation field, range 4-19 cm, mean 12.3 cm). RESULTS: WMC occurred in 37% of the 3DCRT group and 50% of the non-3DCRT group. Among the patients with WMC, Karnofsky performance scale(KPS) deteriorated in none of the 3DCRT group, whereas KPS deteriorated in 3 of 9 in the non-3DCRT group. All the patients with deterioration of KPS were at least 50 years of age. KPS did not strictly correlate with the severity of white matter changes on MRI. Chemotherapy with a platinum drug increased the incidence of WMC. Age(< 50 years vs. > or = 50 years), gender, radiation technique(3DCRT vs. non-3DCRT), radiation dose(< 60 Gy vs. > or = 60 Gy), maximum field-size(< 12 cm vs. > or = 12 cm), and maximum boost-field size(< 10 cm vs. > or = 10 cm) were not relevant to the incidence and severity of WMC. CONCLUSION: Though 3DCRT did not decrease the incidence and severity of white matter change on MRI, it may be useful to preserve the KPS, especially for older patients.

Adolescent↗
PubMed1991

Norepinephrine kinetics and cardiac output during nonhypotensive lower body negative pressure.

Recently we have shown that arterial norepinephrine (NE) concentration increases significantly during lower body negative pressure (LBNP) of -15 mmHg. Interestingly, the increase was found to be related predominantly to a decrease in arterial NE clearance. We postulated that this reduction in clearance would be related to a reduction in cardiac output. Accordingly, we measured both cardiac output (2-dimensional echocardiographic/Doppler technique) and arterial NE kinetics ([3H]NE continuous infusion radiotracer technique) during LBNP of -15 mmHg. These measures of cardiac output and arterial NE spillover and clearance were obtained in 12 normal subjects at baseline, 5 and 10 min (Early) and 25 and 30 min (Late) of LBNP. We found that arterial NE concentration increased significantly, by 25% Early and 22% Late (P = 0.001). Spillover, however, did not change (P = 0.258), whereas clearance decreased by 12% Early and 19% Late (P = 0.014), and cardiac output decreased by 15% Early and 19% Late (P = 0.001). These reductions in clearance and cardiac output correlated significantly (r = 0.61, P = 0.001). No correlation was noted between spillover and cardiac output (r = 0.027, P = 0.874). We conclude that the increases in arterial NE concentration during nonhypotensive LBNP are predominantly due to decreased cardiac output with resultant decreases in systemic clearance of NE. These findings suggest that the ability to clear NE from the circulation is linked to the level of cardiac output and that low cardiac output states by themselves may lead to an elevation in arterial plasma NE concentrations.

Adult↗
PubMedDate not supplied

Cardiac patch constructed from human fibroblasts attenuates reduction in cardiac function after acute infarct.

The current experiments used a scaffold-based, three-dimensional, human dermal fibroblast culture (3DFC) as a cardiac patch to stimulate revascularization and preserve left ventricular (LV) function of the infarcted LV in severe combined immunodeficient (SCID) mice. The 3DFC contains viable cells that secrete angiogenic growth factors and has been previously shown to stimulate angiogenesis. The hypothesis tested was that a 3DFC cardiac patch would attenuate a reduction in LV function of infarcted hearts. Five groups of mice were studied, including normal SCID mice (n = 13), normal SCID mice with 3DFC (n = 6), infarcted SCID mice (n = 6), infarcted mice with nonviable 3DFC (n = 6), and infarcted SCID mice with 3DFC (n = 6). An occlusion of a branch of the left anterior descending (LAD) coronary artery was performed by thermal ligation, and 3DFC was sized to the damaged area and implanted onto the epicardium at the site of tissue injury. Fourteen days postsurgery, LV mechanics were characterized with the Millar conductance catheter system (CCS). The data demonstrated that 3DFC-treated infarcted myocardium had significantly higher ejection fractions (EFs) compared with infarct-only mice (58.9 +/- 10.8 versus 31.0 +/- 5.8%, respectively; p < 0.05). Preload recruitable stroke work (PRSW) parameters were significantly higher in 3DFC-treated mice compared with infarct-only mice (64.6 +/- 11.9 versus 36.8 +/- 6.4 mmHg, respectively; p < 0.05). These results show that the 3DFC as a cardiac patch functioned to attenuate further loss of LV function accompanying acute myocardial infarct and that this may be related in part to myocardial revascularization.

Animals↗
PubMed1997

Regional wall motion during pacing for hypertrophic obstructive cardiomyopathy.

In order to assess the influence of right ventricular stimulation on LV contraction sequence in hypertrophic obstructive cardiomyopathy (HOCM), we performed a regional wall-motion analysis of the left ventricle by comparing normal His-Purkinje activation to pacing from the right ventricular apex. In 9 patients (5 males and 4 females, mean age 61 +/- 9 years) assessed after a mean pacing period of 12 weeks (range 7-24 weeks), AV sequential pacing induced a 52% reduction in maximal pressure gradient from 76 +/- 36 to 40 +/- 28 mmHg (P < 0.01) as determined by Doppler examination. Regional wall-motion analysis of the left ventricle was computed from digitized two-dimensional echocardiographic images by means of the area shrinking method. Pacing induced a significant reduction of total septal area shrinking from 25% +/- 17% to 12% +/- 17% (P < 0.005). A tendency toward paradoxical septal motion was observed in one patient only. The apex showed no significant variation. A 6% increase in area shrinking was observed at the posterior wall and lateral free wall, from 38% +/- 13% to 43% +/- 10% (P < 0.05). Pacing did not significantly alter the global ejection fraction. A direct correlation between the magnitude of subaortic pressure gradient reduction and that of septal motion changes was found in a majority of patients. In conclusion, dual chamber pacing reduces septal wall motion in patients with HOCM obstructive cardiomyopathy. This might be one of the mechanisms involved in the reduction of LV outflow tract obstruction.

Cardiac Pacing, Artificial↗
PubMed2004

Regression of left ventricular mass in hypertensive patients treated with perindopril/indapamide as a first-line combination: the REASON echocardiography study.

BACKGROUND: Increase in left ventricular mass (LVM) may be linked to morbidity and mortality in hypertensive patients. Arterial stiffness, systolic blood pressure (BP), and pulse pressure (PP) seem to be the main determinants of LVM. The perindopril/indapamide combination normalizes systolic BP, PP, and arterial function to a greater extent than atenolol. The aim of this study was to compare the effects of perindopril (2 mg)/indapamide (0.625 mg) first-line combination with atenolol (50 mg) on LVM reduction in hypertensive patients. METHODS: Two hundred fourteen patients with essential hypertension participating in the PREterax in Regression of Arterial Stiffness in a ContrOlled Double-BliNd (REASON), randomized, double-blind, parallel-group study, underwent M-mode two-dimensional-guided echocardiography. RESULTS: Perindopril/indapamide and atenolol were both effective at brachial BP reduction during the 12-month period. The systolic BP reduction was significantly greater with perindopril/indapamide than with atenolol (-21.2 v -15.3 mm Hg), whereas the reduction in diastolic BP was similar between treatment groups (-12.1 v -11.3 mm Hg). Reduction in LVM was higher with perindopril/indapamide than with atenolol. The between-group difference was significant for LVM (-13.6 v -4.3 g, P = .027), LVM/body surface area (LVMI1, P = .032), and LVM/body height2.7 (LVMI2, P = .013). The 124 patients with LV hypertrophy at baseline showed greatest LVM regression (LVM: -22.5 v -8.9 g, P = .009; LVMI1, P = .031; LVMI2, P = .028). The reduction in LVM adjusted for brachial systolic BP and heart rate was still significantly greater with perindopril/indapamide than with atenolol. CONCLUSIONS: Treatment, based on a first-line perindopril/indapamide combination in hypertensive patients, was more effective than atenolol on regression of echocardiographic indices of LVM and LV hypertrophy.

Adult↗
PubMedDate not supplied

A nondenaturing protein map of human plasma proteins correlated with a denaturing polypeptide map combining techniques of micro two-dimensional gel electrophoresis.

Human plasma proteins were separated by combining four types of two-dimensional electrophoresis (2-DE) techniques to obtain systematic information on proteins and their constituent polypeptides. A micro gel system was employed to facilitate the analysis. A plasma sample was first analyzed under nondenaturing conditions of electrophoresis (Type I 2-DE) to characterize the properties of proteins under physiological conditions. The sample was then analyzed, employing nondenaturing isoelectric focusing in the first dimension and sodium dodecyl sulfate (SDS) electrophoresis in the second dimension (Type II 2-DE), to study the dissociation of noncovalently bound protein subunits. In the third type of 2-DE (Type III 2-DE), proteins were separated by nondenaturing isoelectric focusing and treated with urea/mercaptoethanol/SDS and then subjected to second-dimension SDS electrophoresis, to study the dissociation of disulfide-bonded polypeptides. In the fourth type of 2-DE (Type IV 2-DE), the conditions of denaturing 2-DE were employed; the sample was treated with SDS-mercaptoethanol-urea-Nonidet P-40, separated by denaturing isoelectric focusing, and then subjected to SDS electrophoresis. The combined 2-DE technique will be useful to construct a comprehensive database of plasma proteins combining a "nondenaturing protein map" (a protein map) and a "denaturing protein map" (a polypeptide map).

Adult↗
PubMed2005

Molar enamel thickness in the chacma baboon, Papio ursinus (Kerr 1792).

Modern humans exhibit increasing relative enamel thickness from M1 to M3. Some biomechanical (basic lever) models predict that the more distal molars in humans encounter higher occlusal forces, and it has been postulated that this provides a functional explanation for the observed gradient in relative enamel thickness. However, constrained three-dimensional models and experimental observations suggest that there is a reduction in bite force potential from M1 to M3, which would be consistent with the tendency for humans to reduce the size of the distal molars. In this regard, it has been postulated that the distal increase in enamel thickness is a consequence of crown size reduction; thus, it is unnecessary to invoke functional scenarios to explain this phenomenon. We assess these competing proposals by examining relative enamel thickness in a catarrhine primate (Papio ursinus) that exhibits crown size increase from M1 to M3. The molar row of P. ursinus is positioned relatively far forward of the temporomandibular joint, which results in the baboon being able to exert relatively greater muscle forces during posterior biting in comparison to modern humans. Thus, a significant distalward gradient of increasing enamel thickness would be expected in P. ursinus according to the hypothesis that posits it to be functionally related to bite force. The present study reveals no significant difference in relative enamel thickness along the molar row in P. ursinus. This finding lends support to the notion that the relatively thicker enamel of human distal molars is related primarily to their reduction in size. This carries potential implications for the interpretation of enamel thickness in phylogenetic reconstructions: the relatively thick molar enamel shared by modern humans and some of our fossil relatives may not be strictly homologous, in that it may result from different underlying developmental mechanisms.

Anatomy, Cross-Sectional↗
PubMed1989

Application of an affinity electrophoretic and in situ oxidation method to the study of the equine protease inhibitory proteins.

An affinity method was developed to investigate the interaction between protease and protease inhibitor by incorporating a protease incubation step into a two-dimensional electrophoretic separation of the plasma protease inhibitory proteins. This involved the application of the isoelectric focusing gel to filter paper saturated in the protease of choice before being placed on the second-dimensional polyacrylamide electrophoresis gel. General protein staining or immunoblotting was used to detect the protein or ligand in the complex. An in situ oxidation method was developed using the reagent chloramine T to investigate the effect of this reagent on the complexing abilities and inhibitory activities of the protease inhibitory proteins. Oxidation was performed either after electrophoresis prior to staining for enzyme inhibition or during two-dimensional electrophoresis prior to the aforementioned protease incubation. The latter allowed the effect of oxidation on complex formation to be examined. Whole plasmas were utilized as the sources of protease inhibitory proteins with the human and mouse being used as models. The equine protease inhibitory system was examined by the two methods and shown to consist of three classes of inhibitory proteins based on their susceptibilities to oxidation and abilities to form complexes with various proteases.

Animals↗
PubMed2004

Proteomic analysis of hyperoxia-induced responses in the human choriocarcinoma cell line JEG-3.

Living cells exposed to changes in the surrounding oxygen tension, have the ability to adapt to the new environment through the regulatory effect of intracellular mediators. In an effort to identify important proteins that may be involved in the hyperoxic response, we performed proteomic analysis on the human choriocarcinoma cell line JEG-3, incubated under high oxygen tension (carbogen, 95% O2/5% CO(2)) or air (21% oxygen/5% CO(2)). We identified 13 protein spots that were significantly down-regulated (p < 0.05) in JEG-3 cells incubated under hyperoxic conditions compared to standard conditions. Ten of these spots were positively identified by matrix-assisted laser desorption/ionization time of flight-mass spectrometry as nine different proteins: Villin 2, tublin beta, profilin I, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate mutase, peroxiredoxin 1, neuroplypeptide h3, poly(rC)-binding protein 1 and cyclophilin A. These proteins have been implicated in regulating cytoskeletal structure, glycolysis, redox status, signal transduction, transcription and protein folding. The data obtained are consistent with the roles of these proteins in mediating cellular response to oxidative stress and in regulating cell proliferation and motility.

Cell Line, Tumor↗
PubMed1994

Structures of the N-linked oligosaccharides of the membrane glycoproteins from three lepidopteran cell lines (Sf-21, IZD-Mb-0503, Bm-N).

The primary structures of the Asn-linked carbohydrate chains isolated from membrane glycoproteins of the three insect cell lines Mamestra brassicae (Mb-0503), Bombyx mori (Bm-N), and Spodoptera frugiperda (Sf-21) have been determined. Tryptic glycopeptides derived from the membrane fraction were digested with peptide-N-glycanase A. The resulting oligosaccharides were reductively aminated with 2-aminopyridine and identified by two-dimensional HPLC mapping in combination with exoglycosidase digestions. Oligomannose-type structures ranging from Man2GlcNAc2 to Man9GlcNAc2 occurred in all three cell lines. The pattern of Man5- to Man9GlcNAc2-isomers suggests an alpha-mannosidase trimming pathway very similar to that in mammalian cells. In each cell line, the small (Man2, Man3) oligosaccharides were partly fucosylated at the asparagine-linked GlcNAc residue, but distinct fucosylation patterns were observed: while only a low degree of alpha 1,3-fucosylation was detected in Sf-21 and Bm-N cells, the glycoproteins isolated from Mb-0503 cells contained 30% of alpha 1,3-fucosylated glycans, predominantly in the difucosylated form, i.e., with two fucoses linked to the same N-acetylglucosamine residue. Additionally, the following alpha 1,6-fucosylated (Bm-N cells) or difucosylated (Sf-21, Mb-0503 cells) GlcNAc-terminated structures were found: [formula: see text]

Animals↗
PubMed1982

Echocardiographic diagnosis of tricuspid valve endocarditis in a child with a normal heart. Special emphasis on surgical considerations.

A previously healthy 8-year-old girl with a normal heart had development of tricuspid valve staphylococcal endocarditis. Serial two-dimensional echocardiograms first demonstrated an enlarging vegetation and later showed reduction in its size coincident with a pulmonary embolus. The occurrence of the pulmonary embolus along with persistent fevers, despite adequate antibiotic treatment, prompted surgical intervention. Surgical excision of a large residual vegetation, valve debridement, and pulmonary embolectomy led to prompt subsidence of fever and improvement in the patient's condition. Three months after surgery, the child remained asymptomatic with minimal tricuspid insufficiency. However, by eight months after surgery, the hemodynamic consequences of the tricuspid insufficiency had progressed, and the patient is mildly symptomatic. Additional tricuspid valve repair or replacement is expected.

Child↗
PubMed1992

Application problems of a biomechanical model in improving roofwork.

The compression force during traditional roofwork and improved roofwork was calculated by means of a two-dimensional static biochemical model. The improvement resulted in a 30% reduction in compression force, but also influenced factors which cannot be incorporated into the model but may cause back injuries. The frequency and velocity of movements were reduced and the trunk torsion increased. It is recommended that in further development this trunk torsion should be avoided. For valid application of biomechanical models in ergonomics, further research is needed. Priority should be given to epidemiologic research to establish the influence of compression force, trunk torsion and latero-flexion, frequency and velocity of movement on the development of lumbar injuries.

Journal Article↗
PubMed1983

Pig sperm tail tubulin. Its extraction and characterization.

Axonemal tubulin extracted from pig sperm tails has been characterized by one- and two-dimensional electrophoresis and by one-dimensional peptide mapping. The electrophoretic mobilities of its subunits after reduction and carboxymethylation were similar to those of the major subunits of pig brain tubulin. Sperm tail tubulin subunits also had roughly the same isoelectric points as pig brain tubulin subunits, except that they appeared to have a relatively larger tailing effect. The proteolytic cleavage pattern of the pig sperm tail beta-tubulin closely resembled those of both the tunicate (Ciona intestinalis) sperm beta-tubulin and pig brain beta-tubulin. The peptide pattern of pig sperm tail alpha-tubulin, however, was more similar to that of tunicate sperm tail alpha-tubulin than to that of pig brain alpha-tubulin. This supports the hypothesis put forward in a previous investigation [1] that functionally similar tubulins from taxonomically distant species can be more related than functionally dissimilar tubulins from the same species.

Animals↗
PubMedDate not supplied

Changes in glomerulotubular dimensions, single nephron glomerular filtration rates and the renin-angiotensin system in hypothyroid rats.

Glomerular diameters (GD) and lengths of attached proximal convoluted tubules (TPL) were measured in nephrons dissected from the superficial (S), intermediate and juxtamedullary (JM) cortex (7-15 each) of acid-macerated kidneys of weight-matched (E) euthyroid and (H) hypothyroid (2-6 months after radioiodine treatment or thyroidectomy) male Sherman-Wistar rats. Incoordination of growth in H rats was evident in a more marked retardation in kidney than in total body growth. A similar incoordination of microstructural growth was evident in maintenance or GD within normal limits with respect to body weight while attached TPL fell 23% on the average below control values relative to body weight. These changes affected the total nephron population uniformly. As a result, GD/TPL in all nephrons increased significantly (p less than 0.01), by 27% in S and by 29% in JM nephrons. The glomerulotubular dimensional imbalance was associated with a marked and uniformly distributed reduction in single nephron glomerular filtration rate (ferrocyanide method), by 36% in S and JM nephrons. Plasma renin activity fell within normal limits while plasma renin substrate was decreased to 56% of control values. These findings are construed as evidence that growth retardation in hypothyroid rats affects the parenchyma of the kidney (and perhaps other viscera) more than the vasculature.

Angiotensin II↗
PubMed1994

Dimensionality alterations of the hippocampal electroencephalographic activity following the induction of long-term potentiation in rats.

In the present in vivo experimental study the complexity alterations of the hippocampal electroencephalographic (EEG) activity were investigated prior and during the maintenance phase of long-term potentiation (LTP), using analytical methods based on the recent concepts of deterministic chaos. LTP was induced in the hippocampal dentate hilus after stimulation of the medial perforant path of the rat's brain. During the experimental procedure hippocampal EEG epochs were recorded prior and after the induction of LTP. Dimensionality computations performed on these epochs showed a maintained relative reduction in the correlation dimension during the maintenance phase of LTP. This result might suggest that different functional states of the brain are governed by different degrees of complexity and that the altered efficacy in the information process, as it is achieved by the induction of LTP, modifies the spontaneous EEG activity of the potentiated hippocampal area in a plastic manner.

Animals↗