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At least 1,441 records · Page 80Linked to original sources
PubMed2006

Conceptual, methodological and computational issues concerning the compartmental modeling of a complex biological system: Postprandial inter-organ metabolism of dietary nitrogen in humans.

A multi-compartmental model has been developed to describe dietary nitrogen (N) postprandial distribution and metabolism in humans. This paper details the entire process of model development, including the successive steps of its construction, parameter estimation and validation. The model was built using experimental data on dietary N kinetics in certain accessible pools of the intestine, blood and urine in healthy adults fed a [15N]-labeled protein meal. A 13-compartment, 21-parameter model was selected from candidate models of increasing order as being the minimum structure able to properly fit experimental data for all sampled compartments. Problems of theoretical identifiability and numerical identification of the model both constituted mathematical challenges that were difficult to solve because of the large number of unknown parameters and the few experimental data available. For this reason, new robust and reliable methods were applied, which enabled (i) a check that all model parameters could theoretically uniquely be determined and (ii) an estimation of their numerical values with satisfactory precision from the experimental data. Finally, model validation was completed by first verifying its a posteriori identifiability and then carrying out external validation.

Adult↗
PubMed1988

Estimate of attenuation coefficient for ultrasonic tissue characterization using time-varying state-space model.

The images generated from ultrasound pulse-echo signals have long been used to aid clinical diagnosis. Recently, there has been a growing interest in quantitatively determining the acoustic parameters of the tissue as a means of classification and diagnosis. For example, the frequency-dependent attenuation is known to be correlated with different diseases in the liver. In this paper we introduce a new technique for estimating the attenuation coefficient. The effect of attenuation on an interrogating signal with a gaussian-shaped spectrum can be obtained by studying the Wigner distribution of reflected rf data based on a one-dimensional signal model. We show that under the condition that the attenuation varies linearly with frequency, the spectral mean of the reflected signal decreases linearly with time. The estimation algorithm models the pulse-echo signal as the output of a second-order time-varying state-space innovations model driven by white noise. The state coupling matrix A and the output coupling vector C vary with time in a known fashion; moreover, they are also functions of an unknown constant parameter theta. The attenuation coefficient, which is one of the elements of theta, can be estimated directly using a recursive system identification algorithm. The algorithm was verified using both computer-generated synthetic data and in-vivo liver data of known diagnosis. The results show correlation between the estimated parameter and the pathological state of the tissue.

Algorithms↗
PubMedDate not supplied

Application of peptide LC retention time information in a discriminant function for peptide identification by tandem mass spectrometry.

We describe the application of a peptide retention time reversed phase liquid chromatography (RPLC) prediction model previously reported (Petritis et al. Anal. Chem. 2003, 75, 1039) for improved peptide identification. The model uses peptide sequence information to generate a theoretical (predicted) elution time that can be compared with the observed elution time. Using data from a set of known proteins, the retention time parameter was incorporated into a discriminant function for use with tandem mass spectrometry (MS/MS) data analyzed with the peptide/protein identification program SEQUEST. For singly charged ions, the number of confident identifications increased by 12% when the elution time metric is included compared to when mass spectral data is the sole source of information in the context of a Drosophila melanogaster database. A 3-4% improvement was obtained for doubly and triply charged ions for the same biological system. Application to the larger Rattus norvegicus (rat) and human proteome databases resulted in an 8-9% overall increase in the number of confident identifications, when both the discriminant function and elution time are used. The effect of adding "runner-up" hits (peptide matches that are not the highest scoring for a spectra) from SEQUEST is also explored, and we find that the number of confident identifications is further increased by 1% when these hits are also considered. Finally, application of the discriminant functions derived in this work with approximately 2.2 million spectra from over three hundred LC-MS/MS analyses of peptides from human plasma protein resulted in a 16% increase in confident peptide identifications (9022 vs 7779) using elution time information. Further improvements from the use of elution time information can be expected as both the experimental control of elution time reproducibility and the predictive capability are improved.

Animals↗
PubMed1991

A reduced sampling schedule for estimating the parameters of the glucose minimal model from a labeled IVGTT.

The minimal model of tracer glucose disappearance allows the measurement in man of important metabolic parameters from a labeled IVGTT (intravenous glucose tolerance test). Usually 30 blood samples are drawn to measure the insulin and the labelled glucose concentration time courses, which provide the data base for the model identification. In this paper, we address the problem of reducing the number of blood samples withdrawn without, however, deteriorating parameter estimation. By using a stepwise approach, largely based on optimal experiment design theory, we have derived a reliable reduced sampling schedule, which comprises only 14 total samples. The practical application of this reduced schedule has been validated by applying it in a new set of human experiments, completely independent of the ones used in the design phase.

Blood Glucose↗
PubMed1993

Speech encoding strategies for multielectrode cochlear implants: a digital signal processor approach.

The following processing strategies have been implemented on an experimental laboratory system of a cochlear implant digital speech processor (CIDSP) for the Nucleus 22-channel cochlear prosthesis. The first approach (PES, Pitch Excited Sampler) is based on the maximum peak channel vocoder concept whereby the time-varying spectral energy of a number of frequency bands is transformed into electrical stimulation parameters for up to 22 electrodes. The pulse rate at any electrode is controlled by the voice pitch of the input speech signal. The second approach (CIS, Continuous Interleaved Sampler) uses a stimulation pulse rate which is independent of the input signal. The algorithm continuously scans all specified frequency bands (typically between four and 22) and samples their energy levels. As only one electrode can be stimulated at any instance of time, the maximally achievable rate of stimulation is limited by the required stimulus pulse widths (determined individually for each subject) and some additional constraints and parameters. A number of variations of the CIS approach have, therefore, been implemented which either maximize the number of quasi-simultaneous stimulation channels or the pulse rate on a reduced number of electrodes. Evaluation experiments with five experienced cochlear implant users showed significantly better performance in consonant identification tests with the new processing strategies than with the subjects' own wearable speech processors; improvements in vowel identification tasks were rarely observed. Modifications of the basic PES- and CIS strategies resulted in large variations of identification scores. Information transmission analysis of confusion matrices revealed a rather complex pattern across conditions and speech features. Optimization and fine-tuning of processing parameters for these coding strategies will require more data both from speech identification and discrimination evaluations and from psychophysical experiments.

Acoustic Stimulation↗
PubMed1978

Heat and mass transfer of a thermal indicator in pulsatile flow through the cardio-pulmonary system. II. Identification of cardiac output.

Hamilton's celebrated formula for cardiac output measurement is simple but its validity is dependent on several methodologic requirements which are not generally fulfilled, particularly in thermal dilution. A quite different method, based on a physico-mathematical model of the indicator dispersion in the circulation, is proposed. It allows direct derivation of cardiac output once the model's parameters have been identified. Combined deconvolution and least squares procedures are used with truncated data for this identification. Numerical tests and application to clinical observations are presented. Both limitations and possibilities of further developments in estimation of pulsatile flow conditions from TD technique are discussed.

Blood Circulation↗
PubMed1999

Non-proline cis peptide bonds in proteins.

In a non-redundant set of 571 proteins from the Brookhaven Protein Data Base, a total of 43 non-proline cis peptide bonds were identified. Average geometrical parameters of the well-defined cis peptide bonds in proteins determined at high resolution show that some parameters, most notably the bond angle at the amide bond nitrogen, deviate significantly from the corresponding one in the trans conformation. Since the same feature was observed in cis amide bonds in small molecule structures found in the Cambridge Structural Data Base, a new set of parameters for the refinement of protein structures containing non-Pro cis peptide bonds is proposed.A striking preference was observed for main-chain dihedral angles of the residues involved in cis peptide bonds. All residues N-terminal and most residues C-terminal to a non-Pro cis peptide bond (except Gly) are located in the beta-region of a phi/psi plot. Also, all of the few C-terminal residues (except Gly) located in the alpha-region of the phi/psi plot constitute the start of an alpha-helix in the respective structure. In the majority of cases, an intimate side-chain/side-chain interaction was observed between the flanking residues, often involving aromatic side-chains. Interestingly, most of the cases found occur in functionally important regions such as close to the active site of proteins. It is intriguing that many of the proteins containing non-proline cis peptide bonds are carbohydrate-binding or processing proteins. The occurrence of these unusual peptide bonds is significantly more frequent in structures determined at high resolution than in structures determined at medium and low resolution, suggesting that these bonds may be more abundant than previously thought. On the basis of our experience with the structure determination of coagulation factor XIII, we developed an algorithm for the identification of possibly overlooked cis peptide bonds that exploits the deviations of geometrical parameters from ideality. A few likely candidates based on our algorithm have been identified and are discussed.

Algorithms↗
PubMedDate not supplied

[Complex study of the tongue mucosa for identification of a person].

Patterns of the dorsal surface of the mucosa of the tongue was studied in order to detect its specific features in 749 normal subjects of both sexes aged 5-85 years (422 men and 327 women). Racial characteristics of the tongue mucosa structure were studied in 114 foreign students from Africa and Asia. Tongues of 272 corpses of both sexes were examined. A complex of modern methods was used: measurements of geometric parameters, plaster models, computer studies, etc. Unidimensional and multidimensional mathematical analysis helped detect the most significant identification signs of the mucosa of the tongue. The results enabled the authors to create a mathematical model of the tongue allowing identification of sex, age, and ethnic appurtenance.

Adolescent↗
PubMed2003

The application of new software tools to quantitative protein profiling via isotope-coded affinity tag (ICAT) and tandem mass spectrometry: II. Evaluation of tandem mass spectrometry methodologies for large-scale protein analysis, and the application of statistical tools for data analysis and interpretation.

Proteomic approaches to biological research that will prove the most useful and productive require robust, sensitive, and reproducible technologies for both the qualitative and quantitative analysis of complex protein mixtures. Here we applied the isotope-coded affinity tag (ICAT) approach to quantitative protein profiling, in this case proteins that copurified with lipid raft plasma membrane domains isolated from control and stimulated Jurkat human T cells. With the ICAT approach, cysteine residues of the two related protein isolates were covalently labeled with isotopically normal and heavy versions of the same reagent, respectively. Following proteolytic cleavage of combined labeled proteins, peptides were fractionated by multidimensional chromatography and subsequently analyzed via automated tandem mass spectrometry. Individual tandem mass spectrometry spectra were searched against a human sequence database, and a variety of recently developed, publicly available software applications were used to sort, filter, analyze, and compare the results of two repetitions of the same experiment. In particular, robust statistical modeling algorithms were used to assign measures of confidence to both peptide sequences and the proteins from which they were likely derived, identified via the database searches. We show that by applying such statistical tools to the identification of T cell lipid raft-associated proteins, we were able to estimate the accuracy of peptide and protein identifications made. These tools also allow for determination of the false positive rate as a function of user-defined data filtering parameters, thus giving the user significant control over and information about the final output of large-scale proteomic experiments. With the ability to assign probabilities to all identifications, the need for manual verification of results is substantially reduced, thus making the rapid evaluation of large proteomic datasets possible. Finally, by repeating the experiment, information relating to the general reproducibility and validity of this approach to large-scale proteomic analyses was also obtained.

Amino Acid Sequence↗
PubMed1996

Identification of proteins by their amino acid composition: an evaluation of the method.

Expression of different genomes can be studied by high-resolution two-dimensional electrophoresis (2-D PAGE). To help these studies, two-dimensional reference maps of different biological tissues and fluids have been built and can be found in the SWISS-2DPAGE database, accessible via the World Wide Web network on the ExPASy molecular biology server. Different techniques were used to identify the polypeptides. At the present time, the method considered to be the fastest and the most cost-effective is amino acid composition analysis (AAC). Proteins, transferred onto polyvinylidene (PVDF) membranes, were submitted to vapor-phase hydrolysis, derivatized with 9-fluorenylmethyl chloroformate (FMOC) and separated on an ODS-Hypersil column. Identification was obtained by using the program 'AACompIdent' available from ExPASy. In this work, different experimental parameters, such as contamination, reproducibility and accuracy, have been assessed. First, it has been found that a major source of contamination was human keratin. Next, amino acids have been classified into 'reliable' and 'nonreliable'. Accordingly, 'bias' and 'weights' were defined for each amino acid, which could be set in the 'AACompIdent' program. Finally, examples of identification, including the use of Edman degradation sequence tagging, are described.

Amino Acid Sequence↗
PubMed2006

Histological identification of syphilis in pre-Columbian England.

Microscopic analyses served to complement the macroscopic identification of venereal syphilis in two of four pre-Columbian skeletons from the site Hull Magistrates Court in England. Diagnosis was based on parameters presented by Schultz ([1994] Origin of Syphilis in Europe, Toulon: Centre Archaeologique du Var, p. 63-67; [2001] Yrbk. Phys. Anthropol. 44:106-147; [2003] Identification of Pathological Conditions in Human Remains, New York: Academic Press, p. 73-109), which characterized venereal syphilis at a histological level. Observation of the microarchitecture of these samples allowed a more comprehensive approach to identification of the disease (processes). In most samples, Polsters and Grenzstreifen (or remnants of such structures) could be identified, suggesting the presence of a chronic, inflammatory disease such as venereal syphilis. Sinous lacunae were also observed in all histological samples, pointing to lytic activity (osteitis). The combination of both proliferative and destructive processes is pathognomonic for syphilis, and histological analyses provided a more accurate diagnosis of this infectious disease in these four individuals. As a result, the histological evidence suggests that venereal syphilis was present in England prior to 1492. This secondary form of evidence supports the macroscopic identification of the disease, and shows the power of a multimethodological approach to paleopathological diagnoses.

Bone and Bones↗
PubMedDate not supplied

[Identification of a multihit model for nonhomogeneous cell population].

A generalized multihit-multitarget model for a nonhomogeneous, with respect to radiosensitivity, population of irradiated cells is presented. The least squares and the maximum likelihood estimation of the model parameters is given. The estimates quality is evaluated by the computer-based study. The results obtained show the possibility of the parametric identification of cell radiosensitivity distribution according to the "dose-response" data.

Cells↗
PubMed2005

Screening of organic halogens and identification of chlorinated benzoic acids in carbonaceous meteorites.

The occurrence of halogenated organic compounds measured as a sum parameter and the evidence of chlorinated benzoic acids in four carbonaceous meteorites (Cold Bokkeveld, Murray, Murchison and Orgueil) from four independent fall events is reported. After AOX (Adsorbable organic halogen) and EOX (Extractable organic halogen) screening to quantify organically bound halogens, chlorinated organic compounds were analyzed by gas chromatography. AOX concentrations varying from 124 to 209 microg Cl/g d.w. were observed in carbonaceous meteorites. Ion chromatographic analysis of the distribution of organically bound halogens performed on the Cold Bokkeveld meteorite revealed that chlorinated and brominated organic compounds were extractable, up to 70%, whereas only trace amounts of organofluorines could be extracted. Chlorinated benzoic acids have been identified in carbonaceous meteorite extracts. Their presence and concentrations raise the question concerning the origin of halogenated, especially chlorinated, organic compounds in primitive planetary matter.

Carbon↗
PubMed2006

Stationary phases in the screening of drug/impurity profiles and in their separation method development: identification of columns with different and similar selectivities.

The classification or characterization of stationary phases based on chromatographic parameters, in general, requires different test solutes/mixtures and several mobile phases. To simplify the classification/characterization of reversed-phase liquid chromatographic columns, to be used in separating drug/impurity profiles, a new test procedure was proposed. It consists of injecting two mixtures of relatively similar active substances applying a standard gradient. The aim was to evaluate from this approach the selectivity differences and overall separation quality of newly tested columns compared to that in an earlier selected set of eight stationary phases. The selectivity differences of the columns were evaluated by correlation coefficient-based weighted-average-linkage dendrograms and color maps. Derringer's desirability functions were used to rank similar stationary phases according to their overall separation quality. Four columns of 27 examined were, for instance, considered different from the earlier selected eight and could be added to the selection. A number of tested stationary phases might be considered as alternatives for some from the initial set. For three columns the newly tested stationary phases did not contain alternatives.

Chromatography, High Pressure Liquid↗
PubMed1991

Interaction of human platelets with laminin and identification of the 67 kDa laminin receptor on platelets.

A microtitre adhesion assay has been developed to define parameters affecting the adherence of washed platelets to laminin. Adherence was optimally supported by Mg2+ and was inhibited by Ca2+ and by anti-laminin Fab fragments, but significant adhesion (75-90% of control) was found both in heparinized plasma containing physiological levels of bivalent cations and in plasma anti-coagulated with EGTA. Adherence was unaffected by platelet activation with ADP but was decreased by 50% by treatment with alpha-thrombin (1 unit/ml, 5 min). Adherence was unaffected by monospecific polyclonal antibodies to glycoprotein (GP) Ib and GPIV, and was normal with platelets from two patients with Glanzmann's thrombasthaenia, indicating that GPIb, the GPIIb/IIIa complex and GPIV are not involved in platelet-laminin interaction. Affinity chromatography of Triton-solubilized membranes on laminin-Sepharose followed by elution with 0.2 M-glycine/HCl (pH 2.85) identified a major band with a molecular mass of 67 kDa in the reduced and of 53 kDa in the unreduced form. This protein gave a positive reaction on Western blotting with a monospecific polyclonal antibody raised against the high-affinity laminin receptor isolated from human breast carcinoma tissue. The adhesion of platelets to laminin was inhibited by two monoclonal IgM antibodies specific to the LR-1 domain of the 67 kDa receptor. The binding protein was surface-oriented, as shown by flow cytofluorimetry and by the fact that it could be iodinated in intact platelets, but it was not labelled by the periodate-borotritide procedure, suggesting that it did not contain terminal sialic acid. The laminin-derived peptides Tyr-Ile-Gly-Ser-Arg and Cys-Asp-Pro-Gly-Tyr-Ile-Gly-Ser-Arg-NH2, which constitute a complementary binding domain in laminin for the 67 kDa receptor, themselves supported platelet adhesion, bound to the receptor and inhibited the adhesion of platelets to laminin. In addition, Fab fragments of anti-Tyr-Ile-Gly-Ser-Arg antibody inhibited platelet adhesion to laminin. These results demonstrate that the high-affinity 67 kDa laminin receptor previously identified in a range of normal and transformed cells and its complementary Tyr-Ile-Gly-Ser-Arg binding domain play an important role in the interaction of platelets with laminin.

Amino Acid Sequence↗
PubMed2003

Cross-spectral analysis of cardiovascular parameters whilst supine may identify subjects with poor orthostatic tolerance.

An easy and low-cost method for identification of subjects prone to orthostatic vasovagal syncope would be of clinical benefit. An orthostatic test with 60 degrees head-up tilt and progressive lower-body negative pressure was performed on 79 patients with histories of unexplained syncope and 26 control subjects. The test was stopped at the onset of presyncope and time to presyncope was taken as a measure of orthostatic tolerance. Spectral and cross-spectral analysis was performed on the supine time series of the R-R interval (ECG) and systolic pressure (Finapres) recorded before the beginning of the test. According to reference values, 38 patients and 11 controls were classified as having poor orthostatic tolerance (PPT and CPT respectively), whereas 41 patients and 15 controls displayed normal orthostatic tolerance (PNT and CNT respectively). The central frequency of the low-frequency (LF approximately equal to 0.1 Hz.) oscillations in PNT and CNT was significantly higher than that in PPT and CPT. In addition, it was significantly linearly correlated with the time of presyncope. Using our test of orthostatic tolerance as a comparison, the LF central frequency allows the classification of subjects with poor or normal tolerance with 80% sensitivity and 82% specificity. These results suggest that the LF central frequency in the supine position may provide a useful index in the diagnosis of orthostatic intolerance.

Adolescent↗
PubMed1988

Identification of individuals at increased risk for AIDS among clinically asymptomatic homosexuals and abusers of intravenous drugs.

Immunological parameters previously shown to constitute an increased risk for progression towards AIDS have been observed in clinically asymptomatic individuals considered to be at risk for this syndrome. These parameters include severely decreased numbers of T helper cells (count below 400/mm3 blood for CD4+ cells were detected in 7 our of 33 HIV antibody-positive, asymptomatic homosexuals and in 3 out of 29 HIV antibody-positive, asymptomatic drug abusers) and elevated serum IgA and IgM levels (found in 7 to 30 percent of these subjects). Furthermore, up to 60% of risk group members showed a decreased lymphoproliferative response to tetanus toxoid as compared to only 11% of so-called low responders in the simultaneously tested healthy controls. Finally, the capacity to mount an immune response to viral glycoproteins was found to be impaired in individuals at risk for AIDS, as indicated by a low serum level of antibodies to tick-borne meningoencephalitis virus antigen in recently vaccinated subjects.

Acquired Immunodeficiency Syndrome↗