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PubMed2001

Age-dependent cell cycle models.

This paper presents age-dependent cell cycle models i.e., models where cell generation time is a random variable given by some distribution function, and the probability of cell division per unit time is a function only of cell age (not, for example, of cell mass). It is shown that there does not exist a stable mass distribution if the cells grow exponentially. In the case of linear growth, conditions for stability of the mass distribution are derived. To show these, the methods different from those considered up till now in the literature, are used. It is also shown that one can consider the cell mass growth as a linear dynamical system with a stochastic perturbation. The sister cell model as an improvement of the Transition Probability Model is derived. Statistical data are obtained for that model, and comparisons are made with some experimental data. As a verification tool, alpha and beta curves, are used.

Animals↗
PubMed2006

A novel method of producing a repetitive dynamic signal to examine reliability and validity of gait analysis systems.

Gait dysfunction is a common functional complaint of clients who seek medical care. Gait dysfunction can be caused by musculoskeletal disorders such as osteoarthritis or fractures, or it can be caused by neuromuscular disorders such as multiple sclerosis or cerebrovascular accident. Decisions made by health care providers working with these clients could be enhanced by the availability of valid and reliable gait measurement. Valid and reliable gait measurement is possible with laboratory-based motion analysis systems, but these are not universally available. Several portable systems collect footfall data and provide a relatively inexpensive alternative to sophisticated motion analysis systems. However, data collected by these portable systems cannot be used with confidence because of the lack of verification of the validity and reliability of the data they collect about movement. This paper describes a novel method of examining test-retest reliability and concurrent validity that produces a signal with minimal variation. To produce repetitive distance and timing events, a cylindrical weight was rolled across the field of both the laboratory motion analysis system and the system to be evaluated. Measures of the weight's movement were taken simultaneously with both systems. A reference point was chosen to allow for comparison between the systems. The spatial measure that was compared between systems was the horizontal distance between successive repetitions of the reference point's vertical position. The temporal measure that was compared between systems was the time between successive repetitions of the reference point's vertical position. The method described in this paper provides a minimally variable repetitive signal that can be used to investigate concurrent validity of gait analysis systems.

Biomechanical Phenomena↗
PubMed2002

Differential expression of a chloride intracellular channel gene, CLIC4, in transforming growth factor-beta1-mediated conversion of fibroblasts to myofibroblasts.

Conversion of fibroblasts into myofibroblasts as mediated by transforming growth factor-beta1 (TGF-beta1) is the most prominent stromal reaction to a number of epithelial lesions including breast cancer. To identify genes which are regulated during this process, the mRNA profiles from primary breast fibroblasts treated with or without TGF-beta1 were analyzed by differential display. Ninety-five differentially expressed transcripts were PCR-cloned and sequenced, and 28 clones were selected for verification in a hybridization array. By use of gene-specific sequence tags, nine differentially expressed genes were identified. One of the clones, identified as CLIC4, a member of the CLIC family of chloride channels, was up-regulated more than 16 times in myofibroblasts and was therefore chosen for further analysis. Using RT-PCR, comparison with CLIC1, CLIC2, CLIC3, and CLIC5 demonstrated that CLIC4 was unique by being up-regulated by TGF-beta1 in myofibroblasts. Immunohistochemistry showed a hitherto unknown, distinctive pattern of CLIC4 expression in breast stroma. Whereas normal breast fibroblasts were devoid of CLIC4 protein expression, myofibroblasts of breast carcinomas were strongly CLIC4-positive. The functional significance of CLIC4 was analyzed in MEF/3T3 fibroblasts by conditional expression using the tetracycline-repressive gene regulation system. In a migration assay, we found that CLIC4 inhibited cell motility by 27%. These results suggest that CLIC4 is differentially regulated in fibroblasts and that its expression contributes to a collective stationary myofibroblast phenotype.

Breast↗
PubMed1997

Correlation between frontal lobe functions and explicit and implicit stem completion in healthy elderly.

The authors investigated the relationship between performance on neuropsychological tests, which were sensitive to medial-temporal and frontal lobe function, and implicit and explicit stem completion in a group of healthy elderly participants (mean age = 77.3 years). Several stem-completion conditions varying in the size of the search space and the specificity of the cues were included. Across conditions, performance on a frontal lobe sensitive test (word fluency) and on medial-temporal tests (California Verbal Learning Test; delayed recall) correlated with explicit stem completion. The correlations between frontal and medial-temporal test performance and implicit stem completion were weaker. However, a relationship was observed between frontal lobe functioning and stem completion when (a) the search space was large and the cues were constrained and (b) when the search space was limited and the cues were relatively unconstrained. Therefore, the role of the frontal lobes in implicit stem completion seems to be to detect bias resulting from prior study, and this involvement can only be revealed when the interaction between the size of the search space and the retrieval cues (a) makes bias detection necessary and (b) allows it to play a role. The stronger involvement of the frontal lobes in explicit stem completion likely reflects strategic retrieval processes, and the medial-temporal lobe involvement may be related to verification processes.

Aged↗
PubMed2004

Analysis of stochastic noise in intensity-modulated beams.

Inverse planning techniques are known to produce intensity-modulated beams (IMBs) that are highly modulated. They are characterized by the fact that they contain high-frequency modulations that are absent in the profiles that are easier to deliver. For the purpose of this study these clinically unwanted fluctuations are being defined as 'noise'. Although these highly modulated solutions are also optimal solutions, as soon as the profiles are being delivered, they become unfavourable with respect to delivery efficiency and the analysis and verification of treatment. The aim of this work was therefore to understand the origins of the structure and complexity of IMBs. Ultimately, if one can characterize the essential features in optimum beam profiles, it might be possible to control the frequency distribution of IMBs and simplify the IMRT planning and delivery process. The study was based on two common optimization techniques: simulated annealing (SA) and gradient-descent (GD). The assumptions made at the start of this work were that the stochastic noise caused by the SA optimization technique is dominant over other sources of noise and that it could be separated out from the essential modulation after convergence of the cost function by averaging minimum-cost fluence profiles. The results indicate that there are three possible sources of stochastic noise in IMBs, i.e. the optimization technique, the cost function and the definition of convergence of that cost function. In terms of the optimization technique itself, it was confirmed that the gradient-descent technique does not introduce stochastic noise in the IMBs. The SA technique does introduce stochastic noise but averaging of minimum-cost fluence profiles does not result in smoother beam profiles. This originates from the fact that this type of noise is not the dominant factor in the optimization, but rather the curvature of the cost function close to the global minimum. It is shown that the choice of initial temperature in the SA optimization technique is crucial for the convergence of the cost function and the frequency distribution of the fluence profiles. If the initial temperature is too small the stochastic noise will get frozen into the fluence profiles and become the dominant component of noise, resulting in very random-looking and difficult to deliver patterns.

Algorithms↗
PubMed2005

On the verification of intransitive noninterference in mulitlevel security.

We propose an algorithmic approach to the problem of verification of the property of intransitive noninterference (INI), using tools and concepts of discrete event systems (DES). INI can be used to characterize and solve several important security problems in multilevel security systems. In a previous work, we have established the notion of iP-observability, which precisely captures the property of INI. We have also developed an algorithm for checking iP-observability by indirectly checking P-observability for systems with at most three security levels. In this paper, we generalize the results for systems with any finite number of security levels by developing a direct method for checking iP-observability, based on an insightful observation that the iP function is a left congruence in terms of relations on formal languages. To demonstrate the applicability of our approach, we propose a formal method to detect denial of service vulnerabilities in security protocols based on INI. This method is illustrated using the TCP/IP protocol. The work extends the theory of supervisory control of DES to a new application domain.

Algorithms↗
PubMed2001

Studies on the matched potential method for determining the selectivity coefficients of ion-selective electrodes based on neutral ionophores: experimental and theoretical verification.

A theory is presented that describes the matched potential method (MPM) for the determination of the potentiometric selectivity coefficients (KA,Bpot) of ion-selective electrodes for two ions with any charge. This MPM theory is based on electrical diffuse layers on both the membrane and the aqueous side of the interface, and is therefore independent of the Nicolsky-Eisenman equation. Instead, the Poisson equation is used and a Boltzmann distribution is assumed with respect to all charged species, including primary, interfering and background electrolyte ions located at the diffuse double layers. In this model, the MPM-selectivity coefficients of ions with equal charge (ZA = ZB) are expressed as the ratio of the concentrations of the primary and interfering ions in aqueous solutions at which the same amounts of the primary and interfering ions permselectively extracted into the membrane surface. For ions with unequal charge (ZA not equal to ZB), the selectivity coefficients are expressed as a function not only of the amounts of the primary and interfering ions permeated into the membrane surface, but also of the primary ion concentration in the initial reference solution and the delta EMF value. Using the measured complexation stability constants and single ion distribution coefficients for the relevant systems, the corresponding MPM selectivity coefficients can be calculated from the developed MPM theory. It was found that this MPM theory is capable of accurately and precisely predicting the MPM selectivity coefficients for a series of ion-selective electrodes (ISEs) with representative ionophore systems, which are generally in complete agreement with independently determined MPM selectivity values from the potentiometric measurements. These results also conclude that the assumption for the Boltzmann distribution was in fact valid in the theory. The recent critical papers on MPM have pointed out that because the MPM selectivity coefficients are highly concentration dependent, the determined selectivity should be used not as "coefficient", but as "factor". Contrary to such a criticism, it was shown theoretically and experimentally that the values of the MPM selectivity coefficient for ions with equal charge (ZA = ZB) never vary with the primary and interfering ion concentrations in the sample solutions even when non-Nernstian responses are observed. This paper is the first comprehensive demonstration of an electrostatics-based theory for the MPM and should be of great value theoretically and experimentally for the audience of the fundamental and applied ISE researchers.

Journal Article↗
PubMedDate not supplied

Kinetic approach to the study of primary production in the ocean.

Theoretical arguments for and experimental verification of the kinetic approach to the study of primary production in the ocean are described. According to some kinetic models the increase in pure primary production in the ocean is proportional not to time, but approximately to the square root of time. Calculation of the pure primary production of the Pacific Ocean, according to data in the literature, allowing for kinetic correction, gives a value of the order of 7 x 10(9)-10 x 10(9) tons CO2 per annum, equivalent to about 10% of the global pure primary production in the present-day biosphere, calculated from seasonal fluctuations in CO2 in the atmosphere. The existence of polycircadian cycles of function of oceanic phytoplankton is demonstrated.

Atmosphere↗
PubMed2006

Longitudinal mixing in meandering channels: new experimental data set and verification of a predictive technique.

Evaluation of longitudinal mixing processes in open channel flows is important in environmental management, requiring the quantification of mixing coefficients. Estimates of these coefficients sufficiently accurate for environmental impact assessments cannot be achieved using current theoretical or semi-empirical methods for natural channels. This inaccuracy is caused by a limited understanding and quantification of the interaction of the dominant mechanisms resulting from natural channel features, such as plan form curvature and changes in cross-sectional shape. Experimental results are presented here from studies conducted in three self-formed channels, developed by known discharges. Longitudinal mixing was investigated at various flow rates within each of the channels by monitoring the development of tracer plumes during transit through the channels. Using an optimisation procedure, coefficients required for solution of the one-dimensional advection dispersion equation (1D-ADE) were found in the range 0.02-0.2m(2)/s. The coefficients were found to vary as functions of longitudinal meander location, channel form and discharge. Predictions of these longitudinal mixing coefficients were made using a mathematical technique requiring only channel form properties and flow rate as inputs. Predicted values were typically within 20% of the measured values, although deviation of up to 50% was found for the lowest discharge in each channel. This large error is likely to have been caused by increased dead zone effects associated with channel bathymetry at low discharges that are not captured by the method. The method was shown to be capable of capturing the variation in the longitudinal mixing coefficient with longitudinal meander location, with channel form and with discharge.

Diffusion↗
PubMed1988

Three-dimensional reconstruction from electron micrographs of disordered specimens. I. Method.

A method is presented for three-dimensional reconstruction from electron micrographs of a specimen containing a disordered collection of identical objects with unknown orientations. All the data from all the images are simultaneously used to obtain an approximately maximum likelihood estimate of the three-dimensional electron density, which is represented as a truncated expansion in a complete orthonormal set of basis functions. Anomalous objects can nevertheless be detected and eliminated. The method remains under statistical control, and a hypothesis test is used to choose the lowest resolution reconstruction that is consistent with the data. Error propagation is quantitatively traced from the micrograph to the reconstructed electron density. Random orientation is not necessary, and prior knowledge of preferred orientation can be used to advantage. Similarly, symmetry in the object is not necessary, but it can be imposed and exploited, if appropriate. Evidence is presented that useful reconstructions can be obtained with only one or two extra tilts from highly disordered specimens, even if the objects are asymmetric. The companion paper discusses in detail the implementation and verification of the method.

Mathematics↗
PubMed1996

Conversion of lysophospholipids to cyclic lysophosphatidic acid by phospholipase D.

Phospholipase D from Streptomyces chromofuscus hydrolyzes lysophosphatidylcholine or lysophosphatidylethanolamine in aqueous 1% Triton X-100 solution. In situ monitoring of this reaction by 31P NMR revealed the formation of cyclic lysophosphatidic acid (1-acyl 2,3-cyclic glycerophosphate) as an intermediate which was hydrolyzed further by the enzyme at a functionally distinct active site to lysophosphatidic acid (lyso-PA). Synthetic cyclic lyso-PA (1-octanoyl 2,3-cyclic glycerophosphate) was found to be stable in aqueous neutral solutions at room temperature. It was hydrolyzed by the bacterial phospholipase D to lyso-PA at a rate which was approximately 4-fold slower than the rate of formation of cyclic lyso-PA. The addition of 5-10 mM sodium vanadate could partially inhibit the ring opening reaction and thus increase substantially the cyclic lyso-PA accumulation. Cyclic lyso-PA may act as a dormant configuration of the physiologically active lyso-PA or may even possess specific activities which await verification.

Hydrolysis↗
PubMed2006

Bias-corrected diagnostic performance of the naked-eye single-tube red-cell osmotic fragility test (NESTROFT): an effective screening tool for beta-thalassemia.

It is being increasingly recognized that a majority of the countries in the thalassemia-belt need a cost-effective screening program as the first step towards control of thalassemia. Although the naked eye single tube red cell osmotic fragility test (NESTROFT) has been considered to be a very effective screening tool for beta-thalassemia trait, assessment of its diagnostic performance has been affected with the reference test- and verification-bias. Here, we set out to provide estimates of sensitivity and specificity of NESTROFT corrected for these potential biases. We conducted a cross-sectional diagnostic test evaluation study using data from 1563 subjects from Central India with a high prevalence of beta-thalassemia. We used latent class modelling after ensuring its validity to account for the reference test bias and global sensitivity analysis to control the verification bias. We also compared the results of latent class modelling with those of five discriminant indexes. We observed that across a range of cut-offs for the mean corpuscular volume (MCV) and the hemoglobin A2 (HbA2) concentration the average sensitivity and specificity of NESTROFT obtained from latent class modelling was 99.8 and 83.7%, respectively. These estimates were comparable to those characterizing the diagnostic performance of HbA2, which is considered by many as the reference test to detect beta-thalassemia. After correction for the verification bias these estimates were 93.4 and 97.2%, respectively. Combined with the inexpensive and quick disposition of NESTROFT, these results strongly support its candidature as a screening tool-especially in the resource-poor and high-prevalence settings.

Adolescent↗
PubMed1995

Stimulation of nuclear import by simian virus 40-transformed cell extracts is dependent on protein kinase activity.

We previously reported that both the nuclear import rate of large karyophilic gold particles and the functional size of the pores are significantly greater in simian virus 40-transformed fibroblasts (the SV-T2 cell line) than in nontransformed BALB/c 3T3 cells. In this study, we found that cytosolic fractions obtained from SV-T2 cultures can increase nuclear transport capacity (both import rate and pore size) when microinjected into BALB/c 3T3 cells. The transport-enhancing function of the extracts can be abolished by the protein kinase inhibitors staurosporine and K252a as well as 5'-p-fluorosulfonylbenzoyladenosine and protein phosphatase 2A, which, although less specific, also interfere with kinase activity. Increases in transport capacity of the same magnitude as that produced by the SV-T2 extracts were obtained by microinjecting protein kinase A or C or recombinant mitogen-activated protein kinase. These data provide further support for the interpretation that the enhancer is a protein kinase. From experiments performed with specific kinase inhibitor peptides, it appears likely that protein kinase C is the active factor in the SV-T2 cytosolic fractions; however, this will require further verification. It was also determined, by using gold particles coated with bovine serum albumin conjugated to synthetic nuclear localization signal peptides that lacked phosphorylation sites, that the enhancer affects the transport machinery rather than the activity of the nuclear localization signals.

3T3 Cells↗
PubMed2004

[An analysis of the pathogenetic significance of irradiations from mobile phones].

The biological effects of irradiations from mobile phones produced on different structures of the living matter, e.g. molecular-genetics, cells, organ-and-tissue, body and population, are analyzed in the paper. Possibilities of the genetic and epigenetic mutations, metabolic shifts, different-type cytopathic effects, oncogenesis induction, allergic conditions and of other processes associated with a certain lesion of the main structural-and-functional systems of microorganisms are elucidated. Irradiations from mobile phones are shown to have obvious effects on the molecular-and-genetic as well as on organ-and-tissue levels. However, contradictory enough data are available at the moment, which hamper a true evaluation of the unfavorable effects of the phenomenon both in respect to separate organisms and to a population as a whole. The offered analytic survey demonstrated distinctly a potential threat coming from a widely spread modern factor with the above threat requiring to be verified yet by special methods. It is equally quite obvious that, a need is shaping up to improve, in the future, the methods of detection and verification of "factor with finally non-established risk" as well as to investigate the potential pathological properties of such factors, which can essentially promote the system of the social-and-hygienic monitoring.

Animals↗
PubMed1995

Bacterial expression and site-directed mutagenesis of a functional recombinant apolipoprotein.

To facilitate structure-function studies of Manduca sexta apolipophorin III (apoLp-III), its nucleotide coding sequence was cloned from a fat body cDNA library by in vitro DNA amplification. The amplification product was cloned in the pET expression vector and introduced into E. coli. After induction, cultures were screened for apoLp-III protein production by immunoblotting with anti-apoLp-III serum. Data obtained indicated the presence of apoLp-III in both cell lysates and media of cell cultures harboring the apoLp-III-pET construct but not in cells containing the parent vector. The protein was isolated from the cell-free supernatant of cultures grown in minimal media 4 h after induction. Verification that the recombinant protein produced was indeed apoLp-III was obtained by electrospray mass spectrometric analysis. Circular dichroism (CD) spectroscopy of the isolated recombinant protein revealed a characteristic content of alpha-helical secondary structure with a further induction of helix upon addition of 50% trifluoroethanol. In urea denaturation studies, monitored by CD, evidence was obtained that recombinant and natural apoLp-III possess indistinguishable thermodynamic properties. In addition, lipid binding assays revealed that recombinant apoLp-III formed stable complexes with phospholipids and was capable of associating with lipoprotein surfaces. Examination of the fluorescence properties of recombinant apoLp-III revealed the presence of a noncovalently associated fluorescent contaminant that was effectively removed by reverse phase HPLC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

The use of a multipurpose phantom for mailed dosimetry checks of therapeutic photon beams: 'OPERA' (operational phantom for external radiotherapy audit).

BACKGROUND AND PURPOSE: This study presents a technical description of the solid multipurpose phantom (MPP) 'OPERA' (operational phantom for external radiotherapy audit) for mailed dosimetry checks of photon beams in reference and non-reference conditions. The aim is to test the functionality of this phantom by comparing the results provided by the local treatment planning system (TPS) with the measurements by film and thermoluminescence dosimeters (TLDs) in a number of clinical conditions. MATERIAL AND METHODS: The polystyrene MPP is constructed to check the following five irradiation conditions: square fields, asymmetrical fields, wedged beams, oblique incidence and influence of inhomogeneities in the field. The absorbed dose on the central beam axis is measured with TLDs for the first three irradiation conditions and the relative dose distributions are verified with film. RESULTS: The 'OPERA' phantom and the corresponding instruction sheets were mailed to radiotherapy centres of 12 different countries, in order to verify its functionality. A good agreement between TPS and the film data is found: the mean deviations between relative dose profiles obtained from film and locally applied TPS data range between -1.2 and 0.4%, except for the short side of the asymmetrical field. The standard deviations (SDs) generally increase off-axis, with a large SD on the asymmetrical side. Considering the TLD results, a mean ratio of measured to stated dose of 0.995+/-0.014 (1 SD), 0.988+/-0.019 (1 SD) and 0.981+/-0.024 (1 SD) for set-up 1 (square field), 2 (asymmetrical field) and 3 (wedged field), respectively, has been found. CONCLUSION: The 'OPERA' phantom can be useful for on- and off-axis verification of the TPS, as well as for mailed dosimetrical checks of photon beams in reference and non-reference conditions.

Film Dosimetry↗
PubMed1998

Reported food intolerance and respiratory symptoms in young adults.

The aim of the study was to assess the ability of the European Community Respiratory Health Survey (ECRHS) questionnaire to provide data on the prevalence, type and reported symptoms associated with food intolerance from a group of young adults in Melbourne. Six hundred and sixty nine randomly selected subjects completed the questionnaire with 553 attending the laboratory for skin-prick tests, anthropometry, and ventilatory function tests. A further 207 symptomatic participants completed the questionnaire, with 204 of them attending the laboratory. Seventeen per cent of all respondents reported food intolerance or food allergy. A wide variety of food items was cited as being responsible for food-related illnesses. Those with current asthma did not report food-related illness more frequently than those without asthma. Respondents who reported respiratory symptoms following food ingestion were more likely to be atopic, to have used inhaled respiratory medications in the previous 12 months, reported less exposure to regular passive smoking over the past 12 months and weighed more. These associations between respiratory symptoms and food intolerance require further prospective investigation and verification. The importance of using appropriate dietary methodology in future studies for determining diet-disease relationships was highlighted by this study.

Adult↗
PubMedDate not supplied

Experiences of identification and differentiation as functions of leprosy, personality and age.

It is a study of sociogenic need satisfactions that determines the homeostasis of 'being' by remaining contingent conditions of perpetuation or debasement of the social 'self'. The paper has a focus on identification satisfaction and differentiation experience of patients of the highly stigmatized leprosy. The study proceeds with an 'Experimental Group--Control-Group' randomized design. Experimental Groups are two, viz., those of Lepromatous and Non-lepromatous patients. 'Control Group' consists of 'disease-free' normal people. The three independent variables are disease types, age, personality factors. The dependent variables are two, viz., score of identification satisfaction and differentiation experience, measured by standardized tools. Each dependent variable has four '3 X 3 X 2' factorial experiments to test 56 'Null Hypotheses'. The sample consists of 360 elements for each one of the eight experiments. Leprosy elements are drawn from the Central JALMA Institute for Leprosy and the 'Kushta Seva Sadan' (Agra). The 'F' test is run for statistical verification of 'Null hypotheses'. Results show presence of 'role-reversion' and 'role negation' of age and personality factors. The disease possesses 'anti-roles'. It does not allow age and personality factors to promote identification satisfaction and to demote differentiation and experience. The disease actively promotes differentiation and demotes identification through its own 'alien system'. The senescents are the greatest sufferers. 'Social Stigma' works a 'social thanatos' and exposes senescents to substantial 'self-erosion'.

Adolescent↗