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PubMed2006

Mathematical modeling of leachates from ash ponds of thermal power plants.

The present study describes the development of empirical models for the prediction of various trace metals i.e., Mn, Cu, Fe, Zn and Pb found in the leachates generated from the ash ponds of various thermal power plants. The dispersion phenomenon of these trace metals followed first order reaction rate kinetics. The empirical models for individual trace metals derived from the lab scale models data correlate well with the real field data with regression coefficients varying from 0.93 to 0.98. The predicted concentrations of the trace metals varied within +/-3% of the observed values in the leachates generated from the ash ponds of four thermal power plants with standard deviation varying from 0.001 to 0.032. The empirical models derived from the study can be applied for prediction of trace metals in leachates generated from similar thermal power plants.

Environmental Monitoring↗
PubMed1983

Structure-activity relationships of estrogens. Effects of 14-dehydrogenation and axial methyl groups at C-7, C-9 and C-11.

Thirty compounds were evaluated in the rat for uterotropic effects, inhibition of gonadotropin release, and competitive displacement of (3H) estradiol-17 beta from uterine cytosolic preparations. 7 alpha-Methylestradiol-17 beta was 150% as active as estradiol-17 beta as an uterotropic agent. Estradiol-17 beta was the most active inhibitor of gonadotropin release. 11 beta-Methylestradiol-17 beta had 124% of the activity of estradiol-17 beta in displacing (3H) estradiol-17 beta from the "estrogen receptor." The 9 alpha-methyl group considerably decreased the potency of estrogens in any of the three assays. The 14-dehydro modification was advantageous only in the estradiol-17 beta 3-methyl ether series. Uterotropic activities and inhibition of gonadotropin release did not parallel. The best compound for inhibiting gonadotropin release, as compared to uterotropic activity, was estrone. The "estrogen receptor" assay data correlated fairly well with uterotropic assay data, but only for compounds having free 3-hydroxyl groups; even so, some exceptions were noted.

Animals↗
PubMed2006

Quantitation of encapsidated recombinant adeno-associated virus DNA in crude cell lysates and tissue culture medium by quantitative, real-time PCR.

Recombinant AAV vectors are produced by transient transfection of mammalian cells. The virus is usually purified from a combination of lysed cells and spent culture medium by HPLC. We have developed a quantitative, real-time PCR assay for quantifying encapsidated single-stranded viral DNA (i.e. DNA-containing virions) in cell lysates and the spent culture medium. This requires extensive DNaseI digestion to reduce the amount of AAV replicative DNA, as well as plasmid and cellular DNA, to negligible amounts. To demonstrate the utility of this assay, we produced recombinant AAV in HeLa cells and five different types of 293 cells. We used primers to the EGFP transgene to detect the production of a recombinant AAV. We assayed the cell lysates and media by both our quantitative PCR assay and a functional transduction assay. The quantitative PCR assay data correlated well with the transduction assay data. Because this assay only requires standard PCR primers and SYBR Green I dye to detect the amplification of the PCR template, it will readily adapt to any target DNA sequence within the recombinant AAV genome. The recombinant AAV vector does not need to express a reporter gene, such as EGFP or beta-galactosidase in order to assay the amount of virus produced.

Benzothiazoles↗
PubMed1990

In vivo intracerebral microdialysis studies in rats of MPP+ analogues and related charged species.

The in vivo dopaminergic neurotoxic properties of 45 MPTP and MPP+ analogues and related compounds were examined by an intrastriatal microdialysis assay in conscious rats. MPP(+)-like toxicity, as evidenced by the irreversible effects on DA release and enhancement of lactate formation, was observed with a variety of structural types although no compound was more toxic than MPP+. The following global structure-toxicity relationships could be derived: (1) only permanently charged compounds showed neurotoxic effects; (2) with the exception of amino groups, hydrophilic substituents abolished toxicity; (3) activity was enhanced by lipophilic groups although increased steric bulk around the nitrogen atom tended to decrease activity; (4) nonaromatic, quaternary systems (methiodide of MPTP, guanidinium derivatives) were only weakly toxic; and (5) certain bi- and tricyclic systems, including putative metabolites of potential endogenous MPTP-like compounds, were weakly toxic. The lack of toxic effects following perfusions with DA itself confirmed that MPTP dopaminergic neurotoxicity is not likely to be mediated by the MPP(+)-induced release of DA. With some interesting exceptions, these in vivo data correlate reasonably well with in vitro data on the nerve terminal uptake properties and the inhibitory effects on mitochondrial respiration of these compounds.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2002

Urinary heparan sulfate proteoglycan excretion in black African women with pre-eclampsia.

BACKGROUND: The heparan sulfate proteoglycan of the glomerular basement membrane is considered to be mainly responsible for the charge selectivity of the glomerular basement membrane. Decreased heparan sulfate proteoglycan results in a decreased anionic charge of the glomerular basement membrane with increased heparan sulfate proteoglycan in the urine, and is believed to be responsible for the proteinuria in pre-eclampsia. AIM: To determine the urinary heparan and chondroitin sulfate proteoglycan levels in women with pre-eclampsia. MATERIALS AND METHODS: Eighty-four patients were studied: 28 were normotensive pregnant, 28 were nonproteinuric hypertensive, and 28 were pre-eclamptic. Urine samples were obtained and urinary glycosaminoglycan concentrations were determined using the dimethyl-methylene blue assay. Plotting absorbance against the concentrations of heparan and chondroitin sulfate proteoglycans drew a standard curve. The concentration of heparan and chondroitin sulfate proteoglycans was read-off from the linear portion of the standard curve. The standard solutions contained 25, 50, 100 and 200 mg/l heparan or chondroitin sulfate. The Mann-Whitney U-test was used to detect differences between the three groups, and the Pearson's correlation coefficient was calculated for clinical data correlation of the pre-eclamptic group. RESULTS: Urinary excretion of heparan sulfate proteoglycan (123.1 +/- 22.1 mg/l) was significantly increased in the pre-eclamptic group compared with the normotensive pregnant group (60.5 +/- 5.1 mg/l; p < 0.0001) and the hypertensive nonproteinuric group (63. 2 +/- 3.7 mg/l; p < 0.0001). Urinary chondroitin sulfate proteoglycan excretion followed a similar pattern, being significantly increased in the pre-eclamptic group (88.86 +/- 9.79 mg/l) compared with the normotensive pregnant group (49.1 +/- 8.49 mg/l; p < 0.0001) and the hypertensive nonproteinuric group (43. 9 +/- 5.7 mg/l; p < 0.0001). A significant Pearson's correlation between 24-h urine output vs. 24-h protein excretion (r = 0.51; p < 0.001), and between loss of HSPG versus 24-h urinary protein excretion (r = 0.72; p < 0.0001) was obtained in the pre-eclamptic group. CONCLUSION: This study demonstrates a reduction of glomerular charge in pre-eclampsia. The strong correlation between the severity of proteinuria and the loss of charge supports the hypothesis that the loss of glomerular charge induces structural changes of the filtration barrier, and may be the mechanism responsible for the proteinuria in pre-eclampsia. Furthermore, the elevated levels of urinary proteoglycan (heparan and chondroitin sulfate proteoglycans) in this disorder show a loss into the urine rather than a neutralization of these macromolecules.

Adult↗
PubMed1989

Comparison of arterial and venous blood lactate kinetics after short exercise.

Seventeen healthy male volunteers participated in this study designed to compare arterial with both arterialized venous and venous lactate kinetics after short exercise. Blood samples drawn before, during, and after bicycle exercise were analyzed continuously for lactate. A mathematical function incorporating two exponential terms was fitted to the arterial, arterialized venous, and venous lactate recovery curves, and the parameters of the mathematical function were compared using a linear regression. All parameters measured on or fitted to the arterialized venous curves correlated well with the respective arterial data (correlation coefficient R = 0.82 to 0.99, P less than 0.001). Among the parameters obtained from the fit to the venous curves, only those describing lactate removal correlated closely with the arterial results. It is concluded that for lactate kinetic studies during recovery following short-term muscular exercise, the information obtained from arterialized venous blood is comparable to arterial blood, whereas the use of venous blood, from the sampling site in this study, appears suitable for determining only the parameters for lactate disappearance. These conclusions are illustrated by the comparison between arterial, arterialized venous, and venous parameters as a function of the work rate of the previously performed exercise.

Adult↗
PubMed1989

Growth and pubertal development of young female gymnasts and swimmers: a correlation with parental data.

Whereas intensive and regular physical training is known to alter female reproductive function, its potential role in growth is still controversial. At the beginning of a longitudinal growth study of young elite female gymnasts (n = 34, 15-25 h/wk training) and moderately trained swimmers (n = 19, 5-15 h/wk), patterns of recalled parental growth and pubertal maturation were compared with those of parents of 25 sedentary school girls. These data were also correlated to the height, weight, pubertal development as well as adult height prognosis of their daughters. Bone age was estimated using the methods of Greulich-Pyle and Tanner (RUS score) and adult height prognosis using the methods of Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT), and Tanner et al. (TW2). Parents of gymnasts were significantly lighter (fathers: P = 0.027; mothers: P = 0.038) and shorter (fathers: P = 0.034; mothers: P less than 0.001) than those of swimmers and controls. Consequently, target heights of gymnasts were also significantly shorter (P less than 0.001). Recalled menarche occurred significantly later (P = 0.030) in mothers of gymnasts who, in turn, grow much alike their mothers. At the first visit, the gymnasts were shorter and lighter for age than swimmers and controls. Their bone age (11.0 +/- 1.3 years, mean +/- SD) was retarded (P less than 0.001) when compared with chronological age (12.6 +/- 1.2 years). Adult height prognosis was lower for gymnasts than for other girls (BP: P less than 0.001; RWT: P = 0.023, TW2: P less than 0.001), but adequate for target height range.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Determination by Skeleton↗
PubMed1996

The in vitro ejection of zinc from human immunodeficiency virus (HIV) type 1 nucleocapsid protein by disulfide benzamides with cellular anti-HIV activity.

Several disulfide benzamides have been shown to possess wide-spectrum antiretroviral activity in cell culture at low micromolar to submicromolar concentrations, inhibiting human immunodeficiency virus (HIV) type 1 (HIV-1) clinical and drug-resistant strains along with HIV-2 and simian immunodeficiency virus [Rice, W. G., Supko, J. G., Malspeis, L., Buckheit, R. W., Jr., Clanton, D., Bu, M., Graham, L., Schaeffer, C. A., Turpin, J. A., Domagala, J., Gogliotti, R., Bader, J. P., Halliday, S. M., Coren, L., Sowder, R. C., II, Arthur, L. O. & Henderson, L. E. (1995) Science 270, 1194-1197]. Rice and coworkers have proposed that the compounds act by "attacking" the two zinc fingers of HIV nucleocapsid protein. Shown here is evidence that low micromolar concentrations of the anti-HIV disulfide benzamides eject zinc from HIV nucleocapsid protein (NCp7) in vitro, as monitored by the zinc-specific fluorescent probe N-(6-methoxy-8-quinoyl)-p-toluenesulfonamide (TSQ). Structurally similar disulfide benzamides that do not inhibit HIV-1 in culture do not eject zinc, nor do analogs of the antiviral compounds with the disulfide replaced with a methylene sulfide. The kinetics of NCp7 zinc ejection by disulfide benzamides were found to be nonsaturable and biexponential, with the rate of ejection from the C-terminal zinc finger 7-fold faster than that from the N-terminal. The antiviral compounds were found to inhibit the zinc-dependent binding of NCp7 to HIV psi RNA, as studied by gel-shift assays, and the data correlated well with the zinc ejection data. Anti-HIV disulfide benzamides specifically eject NCp7 zinc and abolish the protein's ability to bind psi RNA in vitro, providing evidence for a possible antiretroviral mechanism of action of these compounds. Congeners of this class are under advanced preclinical evaluation as a potential chemotherapy for acquired immunodeficiency syndrome.

Amino Acid Sequence↗
PubMed1995

Mapping of regions of physical deletion on chromosome 16q in prostate cancer cells by fluorescence in situ hybridization (FISH).

Recent evidence suggests that a tumor suppressor gene important in the progression of prostatic carcinoma may reside on chromosome 16q. The exact location and identity of this gene are unknown. We used fluorescence in situ hybridization in a novel manner to define more clearly the location of this gene. Region-specific chromosome 16 cosmid contig probes were hybridized directly to interphase prostatic carcinoma nuclei in order to measure physical deletion of chromosomal loci. Fifteen of 30 tumors (50%) showed evidence of physical deletion of 16q24. Other probes were used to test for regions of chromosome 16 deletions in the same specimens, and a map showing a region of common deletion was created. This map showed the proximal terminus of the region of common deletion to be located distal to 16q23.1. These data correlate well with loss of heterozygosity data in the literature and provide further evidence for the presence of a prostatic carcinoma tumor suppressor gene on chromosome 16q.

Chromosome Deletion↗
PubMed1979

The distribution of isoprenoid quinones in streptococci of serological groups D and N.

The isoprenoid quinone contents of streptococci of serological groups D and N were investigated. Streptococcus faecalis, S. faecalis subsp. liquefaciens and S. faecalis subsp. zymogenes strains contained demethylmenaquinones with nine isoprene units as their major isoprenologues. Menaquinones with eight isoprene units predominated in S. faecium subsp. casseliflavus and S. faecium subsp. mobilis whereas menaquinones with nine isoprene units constituted the major components in strains of S. cremoris, S. cremoris subsp. alactosus, S. lactis and S. lactis subsp. diacetylactis. Strains of S. avium, S. bovis, S. durans, S. equinus, S. faecium, S. raffinolactis and S. suis contained neither menaquinones nor ubiquinones. The isoprenoid quinone data correlate well with other kinds of data on these organisms and are of value in the classification of these bacteria.

Enterococcus faecalis↗
PubMed2005

Relationships between standard automated perimetry, HRT confocal scanning laser ophthalmoscopy, and GDx VCC scanning laser polarimetry.

PURPOSE: This study was designed to determine and compare the relationships between visual function measured with standard automated perimetry (SAP) and structure, either as neuroretinal rim area measured with confocal scanning laser ophthalmoscopy (CSLO), or as retinal nerve fiber layer thickness determined by scanning laser polarimetry with variable corneal compensation (SLP-VCC). METHODS: Forty-six healthy subjects and 76 glaucoma patients were examined with SAP, with CSLO by means of the commercially available Heidelberg Retina Tomograph I (HRT), and with SLP-VCC by means of the commercially available GDx VCC. The relationships between SAP, expressed either in the typically used decibel scale or as number of abnormal points in the total deviation probability plot, and CSLO and between SAP and SLP-VCC were described with linear and logarithmic regression analysis for global data and six individual sectors. The relationship between measurements with CSLO and SLP-VCC was fit with linear regression analysis. RESULTS: The relationships between SAP and CSLO and between SAP and SLP-VCC appeared curvilinear for all sectors except the temporal one between SAP and SLP-VCC. For CSLO, a logarithmic fit was significantly better than a linear one for the global data and in the superotemporal and inferonasal sectors. For SLP-VCC, a curvilinear fit was better for the global data and in the superotemporal, superonasal, and inferonasal sectors. CSLO data correlated linearly with SLP-VCC data in all sectors, except temporally. CONCLUSIONS: CSLO and SLP-VCC showed a very similar curvilinear relationship with SAP. The observed curvilinear relationships confirm earlier reports that these imaging devices appear to detect glaucomatous loss earlier than SAP.

Birefringence↗
PubMedDate not supplied

Representation in natural and artificial agents: an embodied cognitive science perspective.

The goal of the present paper is to provide an embodied cognitive science view on representation. Using the fundamental task of category learning, we will demonstrate that this perspective enables us to shed new light on many pertinent issues and opens up new prospects for investigation. The main focus of this paper is on the prerequisites to acquire representations of objects in the real world. We suggest that the main prerequisite is embodiment which allows an agent--human, animal or robot--to manipulate its sensory input such that invariances are generated. These invariances, in turn, are the basis of representation formation. In other words, the paper does not focus on representations per se, but rather discusses the various processes involved in order to make learning and representation acquisition possible. The argument structure is as follows. First we introduce two new perspectives on representation, namely frame-of-reference, and complete agent. Then we elaborate the complete agent perspective and focus in particular on embodiment and situatedness. We argue that embodiment has two main aspects, a dynamic and an information theoretic one. Focusing on the latter, there are a number of implications: Representation can only be understood if the embedding of the neural substrate in the physical agent is known, which includes morphology (shape), positioning and nature of sensors. Because an autonomous mobile agent in the real world is exposed to a continuously changing high-dimensional stream of sensory stimulation, if it is to learn category distinctions, it first needs a focus of attention mechanism, and then it must have a way to reduce the dimensionality of this high-dimensional sensory stream. Learning is very hard because the invariances are typically not found in the sensory data directly--the classical problem of object constancy: it is a so-called type 2 problem. Rather than trying to improve the learning algorithms--which is the standard approach--the embodied cognitive science view suggests a different approach which focuses on the nature of the data: the agent is not passively exposed to a given data distribution, but, by exploiting its body and through the interaction with the environment, it can actually generate the data. More specifically, it can generate correlated data that has the property that it can be easily learned. This learnability is due to redundancies resulting from the appropriate interactions with the environment. Through such interactions, the former type 2 problem is transformed into a type 1 problem, thus reducing the complexity of the learning task by orders of magnitude. By observing the frame-of-reference problem we will discuss to what extent these invariances are reflected--represented--in the "neural substrate", i.e. the internal mechanisms of the agent. It is concluded, that representation is not a concept that can be studied in the abstract, but should be elaborated in the context of concrete agent-environment interactions. These ideas are all illustrated with examples of natural agents and artificial agents. In particular, we will present a suite of experiments on simulated and real-world artificial agents instantiating the main arguments.

Algorithms↗
PubMed2000

Cytokines in implantation.

Implantation is a process that involves development, attachment and invasion of the blastocyst into the endometrium. Successful implantation requires appropriate communication between the embryo and maternal endometrium. There is evidence to suggest that cytokines produced by the maternal endometrium and the developing embryo play a crucial role in this signalling process. Although numerous cytokine-receptor pairs are expressed by the maternal endometrium and the embryo during implantation, functional knowledge of these cytokines is limited. Compelling data demonstrating a functional role for cytokines in implantation comes from studies using specific cytokine and cytokine receptor knockout mice. There are limited similar data for human implantation, but clinical correlative data and studies using in vitro models indicate that cytokines may have an important functional role in this process. Cytokines that appear to have a functional role in mammalian implantation include leukaemia inhibitory factor, interleukin 1, hepatocyte growth factor, stem cell factor, macrophage colony-stimulating factor and insulin-like growth factors. As implantation failure is a significant cause of natural and in vitro fertilization pregnancy failure, a better understanding of the functional role of these cytokine-receptor pairs is important for improving the diagnosis and treatment of infertility.

Animals↗
PubMed1981

Interactions of neuroleptic metabolites with dopaminergic, alpha adrenergic and muscarinic cholinergic receptors.

Using the radioligand binding assay, the in vitro potency of three neuroleptic drugs at dopaminergic ([3H]spiroperidol), alpha adrenergic ([3H]WB-4101) and muscarinic cholinergic ([3H]quinuclidinyl benzilate) receptor binding sites was compared to the potency of 12 metabolites of these drugs at the same receptors. Metabolites resulting from the oxidation of the ring sulfur of either thioridazine or fluphenazine were very weak at all three receptors. On the other hand, two metabolites, thioridazine-S-sulfoxide (mesoridazine) and thioridazine-S-sulfone (sulforidazine) were more potent than thioridazine at both the dopaminergic and alpha adrenergic receptors but less potent at muscarinic receptors. The binding data correlated very well with published clinical data on the relative potency and incidence of autonomic and extrapyramidal side effects of these three drugs. Since several of the metabolites which are potent receptor blockers accumulate in the plasma during chronic neuroleptic treatment, it appears that both the therapeutic and side effects of neuroleptic drug treatment are due in large part to metabolites of the administered drug.

Animals↗
PubMed1993

Efficacy of chloroquine on Plasmodium falciparum transmitted at Amani, eastern Usambara Mountains, north-east Tanzania: an area where malaria has recently become endemic.

In order to assess the response of newly endemic falciparum malaria to currently used antimalarials, a field study was conducted in Amani, Tanzania. The efficacy of chloroquine (CQ) on Plasmodium falciparum was assessed by in-vivo and in-vitro methods. Fifty-four patients with pure falciparum malaria were treated with CQ and followed daily for 3 days and weekly for one month. Eighty-three per cent of infections exhibited some degree of in-vivo resistance to CQ (46% RI, 28% RII and 9% RIII). Pretreatment blood samples were obtained from all 54 patients for in-vitro sensitivity testing for CQ, amodiaquine (AQ), quinine (QN), and mefloquine (MQ). In-vitro data correlated well with in-vivo data; 80% of successful isolates were resistant to CQ. Forty-five per cent of successful isolates were resistant to AQ, 2% to QN, and none to MQ. The antimalarial levels yielding 99% inhibition (EC99) for CQ, AQ, QN, and MQ were 12.86, 3.24, 24.09 and 0.81 microM respectively. Urine HPTLC revealed CQ metabolites in 15% of study patients who denied recent CQ ingestion and had a negative Dill-Glazko test. This implies the high rate of CQ resistance observed in this study could be due in part to the widespread use of CQ for self-medication. Although the day 3 mean CQ plasma level was higher for sensitive and RI infections than for RII and RIII infections, the difference did not reach statistical significance. Our study results confirm that P. falciparum transmitted at Amani is highly resistant to CQ.

Adolescent↗
PubMed2006

Gaussian estimation and joint modeling of dispersions and correlations in longitudinal data.

Analysis of longitudinal, spatial and epidemiological data often requires modelling dispersions and dependence among the measurements. Moreover, data involving counts or proportions usually exhibit greater variation than would be predicted by the Poisson and binomial models. We propose a strategy for the joint modelling of mean, dispersion and correlation matrix of nonnormal multivariate correlated data. The parameter estimation for dispersions and correlations is based on the Whittle's [P. Whittle, Gaussian estimation in stationary time series, Bull Inst. Statist. Inst. 39 (1962) 105-129.] Gaussian likelihood of the partially standardized data which eliminates the mean parameters. The model formulation for the dispersions and correlations relies on a recent unconstrained parameterization of covariance matrices and a graphical method [M. Pourahmadi, Joint mean-covariance models with applications to longitudinal data: unconstrained parameterization, Biometrika 86 (1999) 677-690] similar to the correlogram in time series analysis. We show that the estimating equations for the regression and dependence parameters derived from a modified Gaussian likelihood (involving two distinct covariance matrices) are broad enough to include generalized estimating equations and its many recent extensions and improvements. The results are illustrated using two datasets.

Likelihood Functions↗
PubMed1991

Correlations between cardiac imaging and electrophysiological studies: what is the state of the art?

Changes in ventricular activation produced by bundle branch block, pre-excitation, and ventricular tachycardia and pacing have been studied by various cardiac imaging modalities. We reviewed results of previously published and newly generated imaging data correlated with known or measured electrophysiological studies. Echocardiography has been demonstrated to grossly correlate with abnormal ventricular wall motion when activation sequence was altered. However, phase analysis of radionuclide and cine-computed tomography have provided detailed noninvasive activation data that correlated reasonably well with measured electrical activation sequence in both animals and man. Analysis of wall motion may not predict activation sequence when muscle is damaged or excessive translational movement of the heart occurs. Body surface mapping of electrical potentials has the capability to accurately but noninvasively register an electrical activation image of the heart that circumvents the problems of imaging contraction sequence. In the future, body surface potential mapping should be more widely used clinically and experimentally.

Animals↗
PubMed2005

Adaptive design and estimation in randomized clinical trials with correlated observations.

Clinical trial designs involving correlated data often arise in biomedical research. The intracluster correlation needs to be taken into account to ensure the validity of sample size and power calculations. In contrast to the fixed-sample designs, we propose a flexible trial design with adaptive monitoring and inference procedures. The total sample size is not predetermined, but adaptively re-estimated using observed data via a systematic mechanism. The final inference is based on a weighted average of the block-wise test statistics using generalized estimating equations, where the weight for each block depends on cumulated data from the ongoing trial. When there are no significant treatment effects, the devised stopping rule allows for early termination of the trial and acceptance of the null hypothesis. The proposed design updates information regarding both the effect size and within-cluster correlation based on the cumulated data in order to achieve a desired power. Estimation of the parameter of interest and its confidence interval are proposed. We conduct simulation studies to examine the operating characteristics and illustrate the proposed method with an example.

Biometry↗