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PubMed1983

Automatic classification of electromyographic signals.

The results of the application of classification methods to electromyograph signals of weak contractions in normal and myopathic subjects are described. Methods of pattern recognition, previously presented, allow the selection of representative motor unit action potentials. The analysis is done with ordinal qualitative variables obtained by identification of shape descriptive parameters (amplitude, duration, number of phases, number of extrema). From this analysis, characteristic classes for normality and myopathy appear, from which a diagnostic aid by assignment can be made.

Action Potentials↗

PubMed1982

Electrocardiographic diagnosis using digital differentiation.

Electrocardiograms have traditionally been used to obtain diagnostic information about the condition of the heart. Computerization of electrocardiograms and automatic identification of various key parameters is now undertaken in many hospitals and clinics. The technique of digital differentiation is now proposed as an extension of existing computer analysis programs to extract additional diagnostically useful information from electrocardiograms. The technique has been applied to computerized electrocardiograms from a group of subjects suffering from left ventricular hypertrophy, and has been shown to produce results which correlate significantly with the extent of the hypertrophy. It is suggested that incorporation of this technique into existing computer programs would provide the opportunity for large scale evaluation of the technique.

Adult↗

PubMed1985

Development of a program package for modelling biochemical systems.

The development of a program for the identification of a model including up to 15 compartments is presented. The identification of the model parameters with this program package is based upon the improved Gauss Marquardt algorithm. This program, implemented on a microcomputer (Data General Eclipse 64 K RAM), uses a calculation and automatic generation of a partial derivative routine. Thus, starting from the differential equations of the model correctly written, there is no longer any risk of error.

Animals↗

PubMed1986

A comprehensive model describing conduction through the atrioventricular node.

An algorithm which models conduction over two conduction pathways through the atrioventricular (AV) node has been derived and tested. Output from the node has been previously related to input, the coupling intervals of extrastimuli introduced during programmed atrial stimulation. An exponential model of conduction in a single pathway was used with the general form: A2 H2 = K1 + K2 exp (-A1 A2/K3) with K1, K2, K3 parameters The algorithm for identification of dual pathways minimised residual sums of squares from two such functions. Potential 'bifurcation' points were selected by significant deviation of the computed single curve of best fit. The algorithm was tested using data obtained during electrophysiology study. Three trials of programmed stimulation were performed in 15 patients after pacing at 100 bpm. Computations using the model suggested single and dual functions (and therefore pathways) respectively in 19 and 25 of 44 trials. An electrophysiologist independently examining the data usually agreed (83% of trials). As the reasons for discordance were minor the model was reasonably verified.

Adolescent↗

PubMed1989

Cell-mediated cytotoxicity. A highly sensitive and informative flow cytometric assay.

Determination of target cell lysis by cytolytic effectors has typically been achieved by two methods: the release of various markers from the cell, as in 51chromium release assays and the uptake of markers into the cell, as in trypan blue uptake in single cell/conjugate binding assays. Problems associated with these assays might include: (1) poor uptake, (2) nonspecific release, (3) poor statistics, (4) length of assays, or (5) subjectivity. These difficulties prompted the development of a new sensitive flow cytometric assay employing two fluorochromes. PKH-1, a fluorochrome which fluoresces in the green, binds to the cytoplasmic membrane and does not leak or transfer, is used to identify the target cell population. Propidium iodide fluoresces in the red and is used to detect non-viable cells. Use of these two fluorochromes and two parameter analysis allows for identification of four subpopulations in the sample: live effectors, dead effectors, live targets and dead targets. By enumeration of these subpopulations the following information can be calculated: (1) the percent target lysis, (2) effector-to-target cell ratios, (3) viability of the effector cells at the termination of the assay, and (4) viable effector to target cell ratios. The results show that PKH-1 labeling of target cells had no effect on effector-target cell interactions. Excellent correlation was found between this method and the chromium assay, however, due to earlier detection of the lytic event, this method provides a distinct time advantage over current methods.

Animals↗

PubMed1993

Biology and treatment of multiple myeloma.

The uniformly fatal plasma cell malignancy, multiple myeloma (MM), currently represents 10-15% of hematologic neoplasms in the USA and has been steadily increasing in incidence for several decades. Therapeutic alternatives have lagged significantly behind insights into the biology and pathogenesis of this entity. Traditionally felt to be a neoplasm of fully differentiated plasma cells, evidence has been mounting that the self renewing population consist of cells derived from a much earlier compartment; perhaps prior to B-cell lineage commitment or even at the level of an earlier 'stem cell'. Bcl-2 protein overexpression has been almost uniformly seen in both clinical myeloma specimens as well as in myeloma cell lines. The failure to consistently identify the t(14;18) translocation, normally found in follicular lymphomas and characteristically associated with overexpression of bcl-2, implies a unique mechanism in MM. A number of cytokines, including TNF alpha, IL-1 and IL-6 have been found to play a central role not only in the biology of the malignant clone but also in the bony and other systemic manifestations of this disease. Since both IL-6 and bcl-2 protein have been shown to prevent programmed cell death, this may be the unifying event in MM. Standard therapy for MM has been an alkylating agent and corticosteroid. Combination chemotherapy provides more prompt palliation but no clear survival advantage. In advanced stages, adriamycin may offer some survival advantage. High dose chemotherapy with or without stem cell support offers a potentially curative therapeutic approach. New interventions directed at the complex cytokine networks pertinent to the pathogenesis of MM are an exciting new area of investigation. Identification of new prognostic parameters as well as new active agents remains the central theme in clinical myeloma research.

Adult↗

PubMed2004

Quantitative assessment of the reliability of identification by high-performance liquid chromatography-mass spectrometry.

At present, mass spectrometry (MS) is the most reliable method for identification but there is not yet a quantitative equation describing this fact. In this investigation an approach to the quantitative assessment of the reliability of identification by MS is proposed which is useful for determination of the selectivity and the validation of analytical methods. Mass spectra of the analytes are presented as maps in which the characteristic ions and their intensities are used for identification. A formula for the quantitative expression of the significance of these parameters to the reliability and the identification is given. The contribution of the resolution of MS instruments or their possibilities of a multiple fragmentation to the reliability of the identification is shown. This approach makes it possible to compare the reliability of identification with different MS instruments. Despite the small contribution of the separation of the chromatographic column compared to the MS separation, the role of the column in the identification is very important to distinguish isomers because their MS spectra are similar.

Acetonitriles↗

PubMed2006

Gas chromatographic peak identification for polybrominated diphenyl ethers under different temperature programs.

A method has been developed for gas chromatographic peak recognition of polybrominated diphenyl ethers (PBDEs) under different temperature programs. On the basis of an identification database of retention parameters (A, B values) of gas chromatography and retention times of the selected internal standards, the retention times of BDEs can be accurately estimated. In comparison with the experimental retention values, the predicted retention times have been proved to be very accurate. In addition, owing to only a part of BDE analytical standards are available, using 40 BDEs as a training set, the quantitative relationship between retention parameters of BDEs and molecular connectivity indexes has been found. The correlation coefficients are greater than 0.997. The A, B values of all the remaining 169 BDE congeners have been predicted.

Calibration↗

PubMed2004

Beat-to-beat analysis of pressure wave morphology for pre-symptomatic detection of orthostatic intolerance during head-up tilt.

OBJECTIVES: The aim of this study was to noninvasively define the hemodynamic profile characterizing the early response to tilting. BACKGROUND: The mechanisms causing orthostatic intolerance have not been fully elucidated. Usually, patients undergoing tilt test are studied in a time-consuming way. Moreover, the test can cause discomfort to the patient and even be potentially hazardous. METHODS: Nineteen orthostatic intolerant patients (OIP), compared with 22 healthy subjects (HS), performed head-up tilt test while their arterial pressure waveform was noninvasively recorded. We elaborated data using the Pressure Recording Analytical Method to obtain hemodynamic parameters, then analyzing the variables by discriminant analysis. RESULTS: Compared with HS, OIP showed lower stroke volume index (SVI) values even in baseline conditions associated with higher values of systemic vascular resistance (SVR) and heart rate (HR). From the third minute of the tilted position and until symptoms appeared, patients exhibited lower values of blood pressure (BP) and SVI and higher HR values but no difference in SVR. At termination, patients showed a further significant reduction in BP and SVI and a persistent increase in HR. CONCLUSIONS: This investigation underlines: 1) the possibility of beat-to-beat monitoring of hemodynamic changes during tilting; 2) the cardiovascular profile of OIP at rest, characterized by lower SVI and higher SVR and HR; 3) the maladaptive response to postural challenge of OIP mainly identifiable in impaired vascular regulation; and 4) the possibility of detecting parameters that enable prompt identification of the positive response to tiltingin these patients, thus guiding the duration of the test.

Adult↗

PubMed2006

The cost-effectiveness of newer drugs as add-on therapy for children with focal epilepsies.

PURPOSE: Epilepsies in children are complex diseases. Guidelines are needed on the appropriate use of newer versus older anti-epileptic drugs (AEDs). This paper presents an individual patient-sampling model to assess the cost-effectiveness of using newer AEDs as add-on therapy in line with UK prescribing guidance. METHODS: Identification of the relevant parameters and treatment pathways for the model were achieved by a systematic review of the literature and discussions with clinical experts. Data were obtained from the literature and supplemented with data elicited from paediatric neurologists. The model considered paediatric patients over the period of childhood from the age of diagnosis to 18 years. RESULTS: The results suggest that the older and newer AEDs are similar in terms of drug retention rates and the average time in 'good' treatment outcomes. In terms of cost, the results indicate a consistent increase in cost (compared to older AEDs) when all of the newer AEDs are considered. The decision analysis results indicate that there are no important health benefits from the use of newer AEDs when used as add-on therapy. However, the analysis also reveals that the uncertainties in the model are greater than the differences between the drug strategies. CONCLUSIONS: To develop guidelines on the appropriate use of newer AEDs, better information is required from randomised controlled trials as there is insufficient data available in the public domain to accurately estimate the nature of the trade off between older versus newer AEDs.

Adolescent↗

PubMed1989

ColE1 plasmid replication: a simple kinetic description from a structured model.

Time constant analysis illustrates how a complex model for ColE-1-type plasmid replication can be reduced to a simple, realistic description of the overall replication kinetics. The analysis leads to the identification of the key parameters governing plasmid replication and to the estimation of parameters that are difficult to determine experimentally. The overall kinetics of ColE1-type plasmid replication are zerothorder in production and first order in dilution. Experimental data confirm our predictions. Similar analysis of the postulated mechanism for the action of the Rom protein reveals that it has no significant effect on plasmid replication dynamics.

Cell Cycle↗

PubMed2003

Characterisation of HTO diffusion properties by an in situ tracer experiment in Opalinus clay at Mont Terri.

A long-term single borehole diffusion experiment using tritiated water as tracer was carried out in Opalinus clay, an argillaceous rock formation that is accessible at the Mont Terri Underground Research Laboratory, situated in the Swiss Jura. The tracer was diluted in reconstituted formation water and introduced into a packed-off section of a borehole located in saturated rock. Pressure in this interval was maintained equal to the pore pressure of the surrounding rock in order to prevent any hydraulic gradient around the borehole and to avoid advective transport processes. The evolution of the tracer concentration in the injection system was monitored over time. After 1 year of diffusion, the claystone surrounding the interval was retrieved by overcoring the whole borehole and packer system, and by an adjacent oblique borehole. Compressed air was used as drilling fluid to reduce rock disturbances. The recovered overcore was sampled along profiles perpendicular to the borehole wall with a view to determining the tracer-concentration profiles in the rock. To avoid further evaporation of tritiated water, subsamples were immediately transferred into polyethylene bottles and disaggregated by adding a known amount of tracer-free water. Fifteen profiles were determined and showed a decreasing tracer concentration with distance into the rock. The pore-water contents were constant along those profiles, confirming that only very little water was lost during overcoring operations. The evolution of tritium-tracer concentration in the injection system over time and in situ profiles were interpreted with a 3-D numerical simulation of the experiment. That allowed for the identification of the transport parameters (orthotropic diffusion tensor and porosity) by minimising the relative quadratic error between the experimental and simulated data. The fitting is good and the results are consistent with data obtained on drill-core samples. The result of tritiated water is discussed regarding (1) the potential effect of mechanical and/or chemical disturbances around the injection borehole and (2) the specific behaviour of tritiated water.

Aluminum Silicates↗

PubMed2007

Acyl carrier protein phosphodiesterase (AcpH) of Escherichia coli is a non-canonical member of the HD phosphatase/phosphodiesterase family.

The Escherichia coli AcpH acyl carrier protein phosphodiesterase (also called ACP hydrolyase) is the only enzyme known to cleave a phosphodiester-linked post-translational protein modification. AcpH hydrolyzes the link between 4'-phosphopanthetheine and the serine-36 side chain of acyl carrier protein (ACP). Although the existence of this enzyme activity has long been known, study of the enzyme was hampered by its recalcitrant properties and scarcity. We recently isolated the gene encoding AcpH and have produced the recombinant enzyme in quantity (Thomas, J., and Cronan, J. E., (2005) J. Biol. Chem. 280, 34675-34683), thus allowing the first studies of its reaction mechanism. AcpH requires Mn2+ for activity, and thus, we focused on the metal binding ligands in order to locate the active site. Bioinformatic investigations indicated that AcpH and its homologues were weakly related to a phosphodiesterase of known structure, the hydrolyase domain of the bifunctional bacterial protein, SpoT, suggesting that AcpH is a member of the HD family of phosphatases/ phosphodiesterases despite lacking the characteristic histidine of the motif. Indeed, we found that AcpH could be convincingly modeled on the SpoT structure with acceptable parameters, which allowed the identification of putative metal binding ligands. These were then tested by site-directed mutagenesis. Mutagenic removal of any of the putative ligands resulted in a severe or total loss of phosphodiesterase activity. In two cases, the H6Q and D24N proteins, the residual activities could be markedly stimulated by addition of high Mn2+ concentrations, thereby demonstrating a role for these residues in metal binding. We conclude that AcpH is a member of the HD protein family despite the lack of the signature histidine residue.

Amino Acid Sequence↗

PubMed2002

Mechanical characterization of bovine periodontal ligament.

This study is part of a research program that aims to develop a constitutive three-dimensional model of the periodontal ligament (PDL) through the identification of pertinent material parameters. As part of this program, bovine PDL was utilized to establish stress-strain responses under tensile and compressive loading conditions. Fresh bovine molars were secured, frozen and prepared to appropriate dimensional specifications. Bar-shaped specimens that comprised portions of dentine, PDL and bone were produced. Push-pull tests were conducted using a specifically constructed loading machine. Full range monotonic stress-strain diagrams were generated. The effect of a rate increase on cyclic S-E diagrams was also determined. The influence of specimen thickness was expressed in terms of modulus of elasticity, strength, uniaxial maximizer strain, and strain energy density. The overall load-response was heavily hysteretic in compression. On the tensile side, after a steep rise, the curve tended to flatten out asymptotically. Variations in rate that spanned four orders of magnitude had no effect on reciprocal load responses. The E-modulus was in the 4-8 MPa range, the strength of the PDL was 1-2 MPa, the maximizer strain was at 45-60% and the strain energy density ranged between 0.3 and 0.4 MPa.

Alveolar Process↗

PubMed2005

Pharmacokinetic variability of anticancer agents.

The translation of advances in cancer biology to drug discovery can be complicated by pharmacokinetic variation between individuals and within individuals, and this can result in unpredictable toxicity and variable antineoplastic effects. Previously unrecognized variables (such as genetic polymorphisms) are now known to have a significant impact on drug disposition. How can the pharmacokinetic variability of anticancer agents be reduced? This will require the understanding of correlations between pharmacokinetics and treatment outcomes, the identification of relevant patient parameters, mathematical modelling of individual and population pharmacokinetics, and the development of algorithms that will tailor doses to the individual patient.

Adsorption↗

PubMed2004

Prognostic significance of activated cytotoxic T-lymphocytes in primary nodal diffuse large B-cell lymphomas.

Clinical outcome in diffuse large B-cell lymphoma (DLBCL) remains unpredictable, despite the identification of clinical prognostic parameters. Here, we investigated in pretreatment biopsies of 70 patients with DLBCL whether numbers of activated cytotoxic T-lymphocytes (CTLs), as determined by the percentage of CD3-positive lymphocytes with granzyme B (GrB) expression, have similar prognostic value as found earlier in Hodgkin's lymphoma and anaplastic large-cell lymphoma and whether loss of major histocompatibility complex (MHC)-I molecules or expression of the GrB antagonist protease inhibitor 9 (PI9) may explain immune escape from CTL-mediated cell death. Independent of the International Prognostic Index (IPI), the presence of >/=15% activated CTLs was strongly associated with failure to reach complete remission, with a poor progression-free and overall survival time. Downregulation of MHC-I light- and/or heavy-chain expression was found in 41% of interpretable cases and in 19 of 56 interpretable cases PI9 expression was detected. We conclude that a high percentage of activated CTLs is a strong, IPI independent, indicator for an unfavorable clinical outcome in patients with primary nodal DLBCL. Although in part of DLBCL expression of PI9 and loss of MHC-I expression was found, providing a possible immune-escape mechanism in these cases, no correlation with clinical outcome was found.

Adolescent↗

PubMed1980

A Mössbauer spectroscopic investigation of the redox behaviour of the molybdenum-iron protein from Klebsiella pneumoniae nitrogenase. Mechanistic and structural implications.

The redox properties of the nitrogenase Mo-Fe protein from Klebsiella pneumoniae have been monitored by 57Fe Mössbauer spectroscopy between -460 and -160mV (relative to the normal hydrogen electrode). Two redox processes associated with the atoms of the protein were observed. One at -216mV (pH 8.7) was associated with the Fe-Mo cofactor centres in the protein and allowed identification of the Mössbauer parameters of the oxidized form of these centres. The other redox process at -340mV (pH 8.7) was associated with species M5 [Smith & Lang (1974) Biochem. J. 137, 169-180]. This latter redox process may be involved in enzyme turnover. The oxidized form of species M5 interacts magnetically with species M4. The structural implications of the data have been considered in relation to other published data. It is concluded that an unequivocal assignment of the M4 and M5 atoms to Fe-S cluster types is not yet possible.

Chemical Phenomena↗

PubMed2001

Local resection of ampullary adenocarcinomas of the duodenum.

BACKGROUND: Pancreaticoduodenectomy (PD) is considered to be the optimal treatment for ampullary adenocarcinomas. Local resection (LR) is a less invasive and potentially equally effective alternative for cancers with favourable prognostic features. Identification of these prognostic parameters may allow selection of patients suitable for LR. METHODS: Twenty-five patients were treated for a primary Vater's ampulla adenocarcinoma at the Alfred Hospital, Melbourne, Australia, between January 1989 and January 2000. Risk factors for cancer recurrence were evaluated and the specific role of LR was defined. RESULTS: Fourteen patients had PD, five had LR and six had bypass procedures (five biliary stents; one operative bypass). Presenting symptoms included jaundice (64%), abdominal pain (54%) and weight loss (32%). Adenocarcinomas that were resected had a median diameter of 2.5 cm, and were limited to the ampulla in 26% (T1), invaded the duodenal wall in 42% (T2) and infiltrated 2 cm or less into the pancreas in 32% (T1) of cases. Locally resected cancers were confined to the ampulla or invaded the duodenum and recurred in one patient following excision. Six recurrences occurred in total, influenced significantly by T staging (P = 0.009). Patient age, preoperative symptoms, laboratory tests, tumour size, differentiation, ulceration, lymphovascular spread and perineural invasion had no effect on recurrence. Patients undergoing LR had lower morbidity and mortality, reduced blood transfusion requirements and shorter hospital stay than those treated by PD. CONCLUSIONS: T staging predicts the risk of tumour recurrence and can be determined using endoscopic ultrasound. Local resection is a suitable alternative to pancreaticoduodenal resection in patients with T1 and T2 adenocarcinomas with a maximum diameter of 3 cm or less.

Adenocarcinoma↗