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Results for “parameter identification”

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PubMed2003

Migration and differentiation of neural progenitor cells from two different regions of embryonic central nervous system after transplantation into the intact spinal cord.

Transplantation of in vitro-expanded neural stem cells (NSCs) is a potentially powerful tool to repair functions of the injured spinal cord. A prerequisite for the successful transplantation therapy is identification of optimized experimental parameters that can promote maximal survival, extensive migration and selective differentiation of the transplanted NSC population in the spinal cord. To this end, we evaluated the basic characteristics of NSC-like cells from two different donor sources, the embryonic hippocampus and spinal cord, after transplantation into the neonatal spinal cord. Proliferation and differentiation phenotypes of both NSC-like cells can be controlled by the concentration of fibroblast growth factor-2 (FGF-2) in vitro. Both NSC-like cells can survive within the environment of the intact neonatal spinal cord and showed extensive migratory behaviour shortly after transplantation. However, quantitative analysis revealed preferential migration of hippocampus-derived cells in the dorsal white matter. Both NSC-like cells showed restricted phenotype toward the oligodendroglial lineage after transplantation. Transplantation of the mixture of two cell types revealed selective survival of hippocampus-derived NSC-like cells. This study indicates the possibility of transplanting hippocampus-derived NSCs to supply the cell source for immature oligodendrocytes, which are thought to be essential for both the myelination and trophic support of regenerating axons in the dorsal white matter of the spinal cord.

Animals↗

PubMed1985

[Mediastinal CT-staging of bronchial carcinomas].

Forty-three patients with proven bronchogenic carcinoma were evaluated with computed tomography (CT) to search for mediastinal and broncho-pulmonary nodal metastases. Definitive staging was achieved by thoracotomy (34 patients) and mediastinoscopy or transbronchial nodal sampling (9 patients). Three parameters of lymph node appearance on CT were studied to improve the sensitivity and specificity of CT in detecting malignancy in bronchogenic carcinoma: 1) node size, 2) node location and 3) border regularity and definition. 762 clearly defined nodes were studied by CT - 391 metastatic and 371 non metastatic. The most useful CT parameters were node size over 10 mm, and node location, which results in a sensitivity of 80% and a specificity of 88%. A combination of all 3 CT parameters increased sensitivity to 82% and specificity to 90%. These results show clearly, that size is not the only relevant CT-parameter in successful preoperative identification of mediastinal nodal metastases.

Aged↗

PubMed1999

Surface plasmon resonance studies resolve the enigmatic endotoxin neutralizing activity of polymyxin B.

Polymyxin B (PMB), a cyclic cationic peptide antibiotic, despite its severe side effects continues to occupy a premiere position for treating endotoxicosis. Its mode of neutralization of endotoxin has remained elusive for the last three decades. Several synthetic peptide mimics of PMB, capable of binding endotoxin, have been made. However, the binding ability alone appears to be a deceptive indicator of endotoxin neutralizing activity as molecules with similar binding propensities could either sequester or opsonize the toxin. Hence identification of additional physical parameters which describe adequately the outcome of PMB-endotoxin interaction become imperative. Surface plasmon resonance (SPR) studies reported here show that several mimics of PMB despite exhibiting lipopolysaccharide binding affinities comparable with it but, unlike it, do not sequester the endotoxin. These studies thus provide a striking illustration of the difference in the behavior of PMB, vis a vis its mimics toward the endotoxin lamellae, and define further, in chemical terms, mechanism of the action of PMB and allow us to posit that the design of molecules as effective antidotes for sepsis should incorporate the ability to sequester endotoxin specifically.

Amino Acid Sequence↗

PubMedDate not supplied

Feasibility of sternal intraosseous access by emergency medical technician students.

OBJECTIVE: Emergency medical technician-basic (EMT-B) providers are not trained to establish vascular or intraosseous (IO) access on critically ill patients. This study was conducted to examine the feasibility of training EMT-B students to correctly place a commercial sternal IO infusion device (FAST-1). METHODS: Twenty-nine EMT-B students attended a two-hour training session. Subjects were subsequently tested in FAST-1 application using a modified resuscitation mannequin permitting IO needle deployment. Two observers assessed correct IO application and technique. Results were analyzed using descriptive statistics (binomial proportions and medians with 95% confidence intervals). Inter-rater agreement of observations was evaluated using kappa statistics and intraclass correlation coefficients (ICCs). RESULTS: Inter-rater agreement ranged from fair to excellent (kappa = 0.37-1.00) for all parameters except sternal notch identification (kappa = -0.03). Reliabilities of elapsed times were good (ICC = 0.83, 0.31). Correct identification of the sternal notch was accomplished by 28 of 29 students (96.6%; 95% CI: 82.2-99.9%). Correct application of the IO target patch was achieved by 29 of 29 (100.0%; 88.1-100.0%). First-attempt successful IO needle deployment was achieved by 16 of 29 (55.2%; 35.7-73.6%). Overall successful IO needle deployment within four attempts was achieved by 27 of 29 (93.1%; 77.2-99.2%). The protective dome was correctly applied by 27 of 29 (93.1%; 77.2-99.2%). The median time to needle deployment was 27.5 seconds (95% CI: 24-31). The median time to dome placement was 50 seconds (95% CI: 42-55). CONCLUSIONS: EMT-B students with minimal training demonstrated limited success with applying a commercial sternal IO device. Clinical application by EMT-Bs on critically ill patients may be possible with more intensive training.

Adult↗

PubMed2004

Mathematical modeling reveals threshold mechanism in CD95-induced apoptosis.

Mathematical modeling is required for understanding the complex behavior of large signal transduction networks. Previous attempts to model signal transduction pathways were often limited to small systems or based on qualitative data only. Here, we developed a mathematical modeling framework for understanding the complex signaling behavior of CD95(APO-1/Fas)-mediated apoptosis. Defects in the regulation of apoptosis result in serious diseases such as cancer, autoimmunity, and neurodegeneration. During the last decade many of the molecular mechanisms of apoptosis signaling have been examined and elucidated. A systemic understanding of apoptosis is, however, still missing. To address the complexity of apoptotic signaling we subdivided this system into subsystems of different information qualities. A new approach for sensitivity analysis within the mathematical model was key for the identification of critical system parameters and two essential system properties: modularity and robustness. Our model describes the regulation of apoptosis on a systems level and resolves the important question of a threshold mechanism for the regulation of apoptosis.

Apoptosis↗

PubMed1982

HPLC, MS, and pharmacokinetics of melphalan, bisantrene and 13-cis retinoic acid.

High performance liquid chromatographic procedures are described for melphalan, bisantrene, and 13-cis retinoic acid, three important anticancer drugs in various stages of clinical development. The procedures require a rapid and simple sample clean-up followed by a 10-to 20-min chromatographic separation on a reversed-phase C18 column. Precisions are all less than 8% with recoveries greater than 80%. Mass spectrometry confirmation of each drug from patient sample separations is presented to provide unambiguous identification for valid pharmacokinetic parameter determination.

Anthracenes↗

PubMed2006

Correlating gene expression to physiological parameters and environmental conditions during cold acclimation of Pinus sylvestris, identification of molecular markers using cDNA microarrays.

Scots pine (Pinus sylvestris L.) seedlings were grown under different conditions (three field locations, two seasons and two climate room regimes), and then analyzed for freezing tolerance of shoots and roots and for transcript abundance in apical buds based on a cDNA microarray containing about 1500 expressed sequence tags (ESTs) from buds of cold-treated Scots pine seedlings. In a climate room providing long daily photoperiods and high temperatures, seedlings did not develop freezing tolerance, whereas seedlings in a climate room set to provide declining temperatures and day lengths developed moderate freezing tolerance. Control seedlings grown outside under field conditions developed full freezing tolerance. Differences in physiological behavior of the different seedling groups, combined with molecular analysis, allowed identification of a large group of genes, expression of which changed during the development of freezing tolerance. Transcript abundance of several of these genes was highly correlated with freezing tolerance in seedlings differing in provenance, field location or age, making them excellent candidate marker genes for molecular tests for freezing tolerance.

Acclimatization↗

PubMed2005

Design of enhanced agonists through the use of a new virtual screening method: application to peptides that bind class I major histocompatibility complex (MHC) molecules.

A new screening procedure is described that uses docking calculations to design enhanced agonist peptides that bind to major histocompatibility complex (MHC) class I receptors. The screening process proceeds via single mutations of one amino acid at the positions that directly interact with the MHC receptor. The energetic and structural effects of these mutations have been studied using fragments of the original ligand that vary in length. The results of these docking studies indicate that the mutant affinity ranking of long peptides can be practically reproduced with a screening approach performed using fragments of six residues. Fragments of four and five residues could mimic, in some cases, the structural arrangement of the side chains of the full-length peptide. We have compared the structural and energetic results of the docking calculations with experimental data using three unrelated ligand peptides that differ greatly in their affinity for the MHC complex. Analysis of the affinity of the fragments led to the identification of three important parameters in the construction of fragments that mimic the structural and energetic properties of the full-length ligand: the length of the fragment; its intermolecular energy; and the number and localization, internal or terminal, of the anchor residues. The results of this new peptide-design methodology have been applied to suggest new peptides derived from the MUC1-8 peptide that could be used as murine vaccines that trigger the immune response through the MHC class I protein H-2K(b).

Animals↗

PubMed2004

Measures and models of nicotine dependence: positive reinforcement.

This paper addresses the problem of assessing nicotine dependence. The main objective is to develop theory-led suggestions for measures that will be relevant in the early phases of tobacco use, as well as in established smokers. Theoretical models of addiction falling into the general class of 'positive reinforcement theories' were identified and reviewed. From this review a number of drug effects and patterns of behaviour were distilled and categorized as either vulnerability or dependence indicators. A comparison of those features with the International Classification of Diseases (ICD-10) and Diagnostic and Statistical Manual (DSM-IV) diagnostic systems shows that neither system includes detailed assessment of vulnerability indicators. It is argued that measurement of vulnerability indicators, in addition to dependence indicators, may add to the predictive validity of assessments carried out in early career tobacco users, especially where there is limited evidence of established dependence. In addition, it is suggested that examination of measures that differentiate a subgroup of early career smokers termed 'rapid accelerators' may prove profitable and enable identification of the key parameters of nicotine reinforcement.

Diagnostic and Statistical Manual of Mental Disord↗

PubMed1997

Comparison between sporadic cytomegalovirus hepatitis and Epstein-Barr virus hepatitis in previously healthy adults.

In order to determine the factors responsible for the differentiation of cytomegalovirus (CMV) hepatitis and Epstein-Barr virus (EBV) hepatitis, the clinical features and laboratory data of both types of hepatitis were retrospectively analyzed in 20 patients with CMV and 11 patients with EBV. While most signs and symptoms of CMV and EBV hepatitis showed no significant differences, we found that cervical lymph- adenopathy was more common in EBV hepatitis than in CMV hepatitis (p < 0.01). Frequency of epigastralgia was more common in CMV hepatitis than EBV hepatitis (p < 0.05). The percentage of peripheral blood monocytes in the white blood cell count in CMV hepatitis was greater than in EBV hepatitis (p < 0.01). Low CD4 levels and high CD8 levels made CD4/CD8 low in peripheral lymphocytes of both groups of hepatitis. Ten EBV hepatitis patients received antibiotics in the early stage of the disease in which two (25%) developed severe erythematous rashes. Four CMV hepatitis patients received antibiotics and did not develop rashes. Identification of early clinical parameters capable of differentiating CMV hepatitis from EBV hepatitis is important.

Adolescent↗

PubMedDate not supplied

Influence of injection conditions on field tracer experiments.

Calibration of ground water transport models is often performed using results of field tracer experiments. However, little attention is usually paid to the influence, on resulting breakthrough curves, of injection conditions and well-aquifer interactions, more particularly of the influence of the possible trapping of the tracer in the injection wellbore. Recently, a new mathematical and numerical approach has been developed to model injection conditions and well-aquifer interactions in a very accurate way. Using an analytical solution derived from this model, a detailed analysis is made of the evolution of the tracer input function in the aquifer. By varying injection conditions from one simulation to another, synthetic breakthrough curves are generated with the SUFT3D ground water flow and transport finite-element simulator. These tests show clearly that the shape of the breakthrough curves can be dramatically affected by injection conditions. Using generated breakthrough curves as "actual" field results, a calibration of hydrodispersive parameters is performed, neglecting the influence of injection conditions. This shows that neglecting the influence of actual injection conditions can lead to (1) errors on fitted parameters and (2) misleading identification of the active transport processes. Conclusions and guidelines are drawn in terms of proposed methodologies for better controlling the tracer injection in the field, in order to minimize risk of misinterpretation of results.

Calibration↗

PubMed2001

Model of geometrical and smooth muscle tone adaptation of carotid artery subject to step change in pressure.

Recent experimental studies have shown significant alterations of the vascular smooth muscle (VSM) tone when an artery is subjected to an elevation in pressure. Therefore, the VSM participates in the adaptation process not only by means of its synthetic activity (fibronectins and collagen) or proliferative activity (hypertrophy and hyperplasia) but also by adjusting its contractile properties and its tone level. In previous theoretical models describing the time evolution of the arterial wall adaptation in response to induced hypertension, the contribution of VSM tone has been neglected. In this study, we propose a new biomechanical model for the wall adaptation to induced hypertension, including changes in VSM tone. On the basis of Hill's model, total circumferential stress is separated into its passive and active components, the active part being the stress developed by the VSM. Adaptation rate equations describe the geometrical adaptation (wall thickening) and the adaptation of active stress (VSM tone). The evolution curves that are derived from the theoretical model fit well the experimental data describing the adaptation of the rat common carotid subjected to a step increase in pressure. This leads to the identification of the model parameters and time constants by characterizing the rapidity of the adaptation processes. The agreement between the results of this simple theoretical model and the experimental data suggests that the theoretical approach used here may appropriately account for the biomechanics underlying the arterial wall adaptation.

Adaptation, Physiological↗

PubMed1981

Steady and unsteady pressure-flow relationships in central airways.

We measured pressure-flow relationships in a noncompliant five-generation cast of human central airways using air, HeO2, and SF6O2 at 0, 0.25, 0.50, 1.0, and 2.0 Hz with tidal volumes of 0.25, 0.5, and 1.0 liter. When dimensionless pressure drops for steady inspiratory and expiratory flows of the various gas mixture were plotted against Reynolds' number on a log-log scale (Moody diagram), they formed two curves as fluid mechanical theory predicts. At frequencies higher than 0.25 Hz, data obtained from 1) the same gas and same stroke volume, 2) the same frequency and same stroke volume but different gases, and 3) the same gas at the same frequency but with different stroke volumes, all deviated from the steady flow curves in the Moody diagram, always tending to increase the dimensionless pressure drop. The increase was largest when instantaneous flow was near zero and was minimal at the peak flow in a given inspiration or expiration. These data led to the identification of a dimensionless parameter (epsilon) that reflects the relative importance of local acceleration (unsteadiness) to convective acceleration at any given instant during a flow cycle. A dimensional analysis then reveals that the pressure-flow relationship in a given airway system is uniquely and completely determined by a combination of three dimensionless parameters: Reynolds number (Re), Womersley number (alpha), and the new parameter (epsilon). With this set of parameters we can explain all reported apparent paradoxes as well as the present findings.

Airway Resistance↗

PubMed2002

Spike frequency adaptation and neocortical rhythms.

Spike-frequency adaptation in neocortical pyramidal neurons was examined using the whole cell patch-clamp technique and a phenomenological model of neuronal activity. Noisy current was injected to reproduce the irregular firing typically observed under in vivo conditions. The response was quantified by computing the poststimulus histogram (PSTH). To simulate the spiking activity of a pyramidal neuron, we considered an integrate-and-fire model to which an adaptation current was added. A simplified model for the mean firing rate of an adapting neuron under noisy conditions is also presented. The mean firing rate model provides a good fit to both experimental and simulation PSTHs and may therefore be used to study the response characteristics of adapting neurons to various input currents. The models enable identification of the relevant parameters of adaptation that determine the shape of the PSTH and allow the computation of the response to any change in injected current. The results suggest that spike frequency adaptation determines a preferred frequency of stimulation for which the phase delay of a neuron's activity relative to an oscillatory input is zero. Simulations show that the preferred frequency of single neurons dictates the frequency of emergent population rhythms in large networks of adapting neurons. Adaptation could therefore be one of the crucial factors in setting the frequency of population rhythms in the neocortex.

Action Potentials↗

PubMed2006

Differences in expression of cardiovascular risk factors among type 2 diabetes mellitus patients of different age.

Atherosclerotic coronary heart disease and other forms of cardiovascular disease (CVD) are the major cause of mortality in type II diabetes (T2DM) as well as a major contributor to morbidity and lifetime costs. The purpose of this article is the identification of the biochemical parameters in plasma, which may serve as predisposition factors to CVD in T2DM patients of different ages. The variability of hyperglycemia, dyslipidemia, and inflammation with age progression was also studied for comparison. Four different diabetic groups allocated on the basis of the subjects' age (Group A: 15-25 years old; Group B: 26-40 years old; Group C: 40-60 years old; Group D: 60-80 years old) and consisting of 10 patients each, in parallel with 10 healthy controls matched for age, sex, and ethnic origin were screened for glucose, insulin, lipid profile (total cholesterol, triglycerides, LDL, and HDL), and inflammatory mediators (CRP, IL-6, and TNF-alpha). Significant differences were observed among the expressions of biochemical markers among different age groups. Hyperglycemia showed no variability with age whereas dyslipidemia correlated positively with age progression, as well as obesity, low physical activity, and family history of heart disease or diabetes. Marked inflammation was prominent only in Groups C and D. This article indicates that different biochemical parameters may be used for the assessment of CVD risk in T2DM patients of variable age.

Adolescent↗

PubMed2004

Anatomy of a live invertebrate revealed by manganese-enhanced Magnetic Resonance Imaging.

Non-invasive imaging technologies such as Magnetic Resonance Imaging (MRI) are increasingly in demand by researchers in many biological disciplines. However, when imaging small animals such as invertebrates, not only is the use of high-field magnets necessary to gain satisfactory spatial resolution, but the achievement of adequate contrast between tissues also requires the identification of applicable imaging parameters by means of expensive and time-consuming procedures. Here we report that systemically administered manganese can act as an effective MRI contrast agent for quick and non-invasive imaging of the nervous system and other complex anatomical structures in a small aquatic animal. Due to the tendency of manganese ions to differentially accumulate in most soft tissues, higher overall signal intensity and strongly improved contrast between structures yield data well suited for digital post-processing into three-dimensional models. Within a few hours this technique can efficiently generate anatomical images that are not obtainable with conventional methods, thus demonstrating a new and exciting approach to invertebrate research.

Animals↗

PubMed2000

Assessment of the non-linear behaviour of plastic ankle foot orthoses by the finite element method.

The stiffness characteristics of plastic ankle foot orthoses (AFOs) are studied through finite element modelling and stress analysis. Particular attention is given to the modelling and prediction of non-linear AFO behaviour, which has been frequently observed in previous experimental studies but not fully addressed analytically. Both large deformation effects and material non-linearity are included in the formulation and their individual influence on results assessed. The finite element program is subsequently applied to the simulation of a series of tests designed to investigate the relation between AFO trimline location and stiffness for moderate and large rotations. Through careful consideration and identification of key modelling parameters, the developed finite element solution proves to be a reliable and effective alternative means of assessing variations of a typical plastic AFO design so that particular patient requirements could be met, in the long term.

Activities of Daily Living↗

PubMed1995

Determination of the glomerular filtration rate by identification of sinistrin kinetics.

A computer-based method of system identification and estimation of parameter variance for two-compartment models matched to dynamic sinistrin concentration profiles for the determination of glomerular filtration rate is described. Thereby a procedure for the judgment of the optimal sampling time horizon is presented. Since single-injection techniques are suspected of yielding systematic overestimation of the glomerular filtration rate, a method is demonstrated confirming that such a technique employing sinistrin kinetics can be used to correctly determine the glomerular filtration rate. The validation of the system parameters gained by the single-injection method is made through prediction of the concentration contour under a constant infusion regimen in the same subject on a different occasion. This was performed in healthy controls and in patients with various degrees of renal insufficiency. Upon consideration of the dependence of the clearance estimates and their variances on the protocol duration in test subjects examined from four to ten hours, an adaptive design of the protocol length is developed.

Adult↗