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PubMed2000

Valve movement responses of Velesunio angasi (Bivalvia: Hyriidae) to manganese and uranium: an exception to the free ion activity model.

The veracity of the free ion activity model (FIAM) was tested by examining the acute (48 h) valve movement responses (VMR) (measured in terms of the duration of valve opening) of the Australian tropical freshwater unionid bivalve, Velesunio angasi to increasing concentrations of total Mn or U, in a standard synthetic water under conditions of varying pH (5.0-6.0) and/or dissolved organic carbon (model fulvic acid, FA) concentrations (0-8.9 mg l(-1)). Valve movement behaviour, measured using an automated data acquisition system, was shown to be a quantifiable and rapid, real-time endpoint for assessing the toxic effects of Mn and U exposures. For Mn, the VMR of V. angasi were independent (P>0.05) of pH and/or model FA concentration. In contrast, VMR to U exposures were highly dependent (P< or =0.05) on pH and/or model FA concentration; individuals were more sensitive to U at low pH and model FA concentrations. Valve movement responses to Mn were directly proportional to the activity of the free metal ion (Mn(2+)), which is consistent with the FIAM. In contrast, VMR to U were regarded as an 'exception' to the FIAM, since they were a weighted function of the activities of the free metal ion and the 1:1 metal hydroxide species (i.e. 1.86 x UO2(2+) + UO2OH(+)). Additionally, the effect of U on V. angasi demonstrates the importance of examining VMR at more than one pH. At a fixed pH, the results for U were consistent with the FIAM (i.e. response was directly proportional to UO2(2+)); only when pH was altered, were the results inconsistent with the FIAM. The inconsistency in the VMR of V. angasi to U exposures in this study, together with similar examples from other studies using different metals (e.g. Al or Zn), raises questions regarding the veracity of the FIAM. A detailed examination of the conceptual development of the FIAM is required to probe its apparent failure to describe several metal-organism interactions.

Algorithms↗
PubMed2002

Precursors to onset clusters in acquisition.

Two lawful relationships involving word-initial onset clusters have been advanced in the acquisition literature; namely, that clusters imply affricates (Lleó & Prinz, 1996, 1997), and that liquid clusters imply a liquid distinction (Archibald, 1998). This study evaluated and extended the validity of these implicational laws in a population of 110 children (aged 3;0 to 8;6) with functional phonological delays who contributed extended speech samples for computational analyses. Results indicated that, for the most part, the composition of children's sound systems were in compliance with the proposed laws; however, there were noted asymmetries and apparent exceptions in the data. The asymmetries motivated an integration of the two laws to reveal a pattern of segmental-prosodic cyclicity consistent with deterministic models of phonological acquisition. The apparent exceptions highlighted the relevance of independent methodologies and offered a potential theoretical alternative with the Resolvability Principle as directions for future research.

Child↗
PubMed2004

The acquisition of hMLH1 methylation in plasma DNA after chemotherapy predicts poor survival for ovarian cancer patients.

Aberrant epigenetic regulation, such as CpG island methylation and associated transcriptional silencing of genes, has been implicated in a variety of human diseases, including cancer. Methylation of genes involved in apoptosis, including the DNA mismatch repair (MMR) gene hMLH1, can occur in tumor models of resistance to chemotherapeutic drugs. However, the relevance for acquired resistance to chemotherapy of patients' tumors remains unsubstantiated. Plasma DNA from cancer patients, including those with ovarian cancer, often contains identical DNA changes as the tumor and provides a means to monitor CpG island methylation changes. We have examined plasma DNA of patients with epithelial ovarian cancer enrolled in the SCOTROC1 Phase III clinical trial for methylation of the hMLH1 CpG island before carboplatin/taxoid chemotherapy and at relapse. Methylation of hMLH1 is increased at relapse, and 25% (34 of 138) of relapse samples have hMLH1 methylation that is not detected in matched prechemotherapy plasma samples. Furthermore, hMLH1 methylation is significantly associated with increased microsatellite instability in plasma DNA at relapse, providing an independent measure of function of the MMR pathway. Acquisition of hMLH1 methylation in plasma DNA at relapse predicts poor overall survival of patients, independent from time to progression and age (hazard ratio, 1.99; 95% confidence interval, 1.20-3.30; P = 0.007). These data support the clinical relevance of acquired hMLH1 methylation and concomitant loss of DNA MMR after chemotherapy of ovarian cancer patients. DNA methylation changes in plasma provide the potential to define patterns of methylation during therapy and identify those patient populations who would be suitable for novel epigenetic therapies.

Adaptor Proteins, Signal Transducing↗
PubMed2003

A markup language for electrocardiogram data acquisition and analysis (ecgML).

BACKGROUND: The storage and distribution of electrocardiogram data is based on different formats. There is a need to promote the development of standards for their exchange and analysis. Such models should be platform-/ system- and application-independent, flexible and open to every member of the scientific community. METHODS: A minimum set of information for the representation and storage of electrocardiogram signals has been synthesised from existing recommendations. This specification is encoded into an XML-vocabulary. The model may aid in a flexible exchange and analysis of electrocardiogram information. RESULTS: Based on advantages of XML technologies, ecgML has the ability to present a system-, application- and format-independent solution for representation and exchange of electrocardiogram data. The distinction between the proposal developed by the U.S Food and Drug Administration and ecgML model is given. A series of tools, which aim to facilitate ecgML-based applications, are presented. CONCLUSIONS: The models proposed here can facilitate the generation of a data format, which opens ways for better and clearer interpretation by both humans and machines. Its structured and transparent organisation will allow researchers to expand and test its capabilities in different application domains. The specification and programs for this protocol are publicly available.

Decision Support Techniques↗
PubMed1987

Image analysis and X-ray microanalysis in cytochemistry.

When cytochemical reaction products are homogeneously distributed within an organelle, point analyses suffice for the quantitative approach. However, quantitative analysis becomes tedious, when the elements in the reaction product are inhomogeneously distributed. Problems arise when elements from two reaction products have to be related to each other, or to endogenous cytological products (ferritin, haemosiderin, calcium, electron dense markers), either topographically or in concentration. When analyzing inhomogeneous/heteromorphical reaction product-containing organelles special attention has to be paid to measure and relate both volume and concentration. In this paper a relative simple structure (eosinophil granules) is chosen to demonstrate that the acquisition of the requested morphometrical plus chemical information and their integration is possible. The following points will be covered to acquire the morphometrical and chemical information: a). How to estimate the total cell cross-sectioned area. b). How to estimate the total cross-sectioned area of all reaction product-containing particles inside that cell. The ratio of these two areas will provide the requested information about the particle volume fraction. By using the X-ray detector in addition: c). How to acquire the chemical information at the requested resolution, within a reasonable total acquisition time d). How to integrate the morphometrical and chemical data per organelle, by matrix analysis in a reduced scan area. e). How to acquire quantitative chemical information, by the use of cross-sectioned standards. f). How to make this acquisition method independent from changes in the instrumental conditions during the acquisition.

Animals↗
PubMed2001

Multiple lateral transfers of dissimilatory sulfite reductase genes between major lineages of sulfate-reducing prokaryotes.

A large fragment of the dissimilatory sulfite reductase genes (dsrAB) was PCR amplified and fully sequenced from 30 reference strains representing all recognized lineages of sulfate-reducing bacteria. In addition, the sequence of the dsrAB gene homologs of the sulfite reducer Desulfitobacterium dehalogenans was determined. In contrast to previous reports, comparative analysis of all available DsrAB sequences produced a tree topology partially inconsistent with the corresponding 16S rRNA phylogeny. For example, the DsrAB sequences of several Desulfotomaculum species (low G+C gram-positive division) and two members of the genus Thermodesulfobacterium (a separate bacterial division) were monophyletic with delta-proteobacterial DsrAB sequences. The most parsimonious interpretation of these data is that dsrAB genes from ancestors of as-yet-unrecognized sulfate reducers within the delta-Proteobacteria were laterally transferred across divisions. A number of insertions and deletions in the DsrAB alignment independently support these inferred lateral acquisitions of dsrAB genes. Evidence for a dsrAB lateral gene transfer event also was found within the delta-Proteobacteria, affecting Desulfobacula toluolica. The root of the dsr tree was inferred to be within the Thermodesulfovibrio lineage by paralogous rooting of the alpha and beta subunits. This rooting suggests that the dsrAB genes in Archaeoglobus species also are the result of an ancient lateral transfer from a bacterial donor. Although these findings complicate the use of dsrAB genes to infer phylogenetic relationships among sulfate reducers in molecular diversity studies, they establish a framework to resolve the origins and diversification of this ancient respiratory lifestyle among organisms mediating a key step in the biogeochemical cycling of sulfur.

Amino Acid Sequence↗
PubMed2006

Down-regulation of c-Myc following MEK/ERK inhibition halts the expression of malignant phenotype in rhabdomyosarcoma and in non muscle-derived human tumors.

BACKGROUND: Expression of c-myc proto-oncogene is inappropriate in a wide range of human tumors, and is a downstream target of Ras/Raf/ERK pathway, which promotes c-Myc stability by enhancing c-Myc expression and activity. The aim of this study was to investigate whether the oncogenic phenotype in the human muscle-derived Rhabdomyosarcoma (RD) cell line and in non muscle-derived human tumor cell lines (SW403, IGR39 and PC3) can be blocked by disrupting the c-Myc pathway either by means of pharmacological MEK/ERK inhibition or by direct inactivation of the c-Myc protein. RESULTS: We demonstrate that, in all the tumor cell lines used, the MEK/ERK inhibitor U0126 rapidly induces c-Myc de-phosphorylation, which is followed by a marked reduction in its expression level, by inhibition of proliferation and by reversion of anchorage-independent growth. These data suggest that the targeting of pathways controlling c-Myc expression or stability reverses deregulated growth of different tumor-derived cell lines. Indeed, in RD cells, we found a marked down-regulation of cyclins E2, A and B and CDK2, all of which are known to be targets of c-Myc. Moreover, ectopic MadMyc chimera, a c-Myc function antagonist, causes dramatic growth arrest, CDK and cyclin modulation as well as inhibition of anchorage-independent growth in RD cells, as occurs in U0126-treated cells. In particular, we found that the mere inhibition of c-Myc by MadMyc chimera rescues the myogenic program, MHC expression and the acquisition of the myogenic-like phenotype in RD cells. CONCLUSION: Our data provide evidence of the key role played by the MEK/ERK pathway in the growth arrest and transformation phenotype of Rhabdomyosarcoma and of non muscle-derived tumor cell lines. In fact, MEK/ERK inhibitor, U0126, induces growth arrest, anchorage-dependent growth of these cell lines. In addition, the results of this study demonstrate that the direct inactivation of c-Myc by Mad/Myc chimera rescues myogenic program and leads to the reversal of the Rhabdomyosarcoma phenotype. In conclusion these data strongly suggest that the targeting of c-Myc by means of the MEK inhibitor can be tested as a promising strategy in anti-cancer therapy.

Butadienes↗
PubMed1992

Changes of DNA methylation in protooncogenes in the process of radiation-induced transformation of mouse m5S/1M cells in vitro.

To assess the importance of changes in DNA methylation in an X-ray-induced cellular transformation process, methylation patterns of five nuclear protooncogenes in fifteen transformant clones were studied and compared to that of the parental non-transformed cell line m5S/1M. All transformants examined revealed an alteration in DNA methylation in some of the genes, although these changes were variable among them. A comparison of cellular characteristics with corresponding DNA methylation changes in different clones suggested that the loss of contact inhibition and the gain of anchorage independency were associated with increases of methylation in many genes, whereas the acquisition of tumorigenicity was often accompanied by a decrease of methylation in the N-myc and c-myc genes. Resultant data indicate that the alteration of DNA methylation is closely related to transformation process, yet how this involvement occurs is complex and remains unclear.

Animals↗
PubMed1991

The early acquisition of two-way (shuttle-box) avoidance as an anxiety-mediated behavior: psychopharmacological validation.

Several lines of evidence have established that performance during the initial steps of acquisition on a shuttle-box avoidance task is an anxiety-mediated behavior (i.e., the differences between strains selectivity bred for emotionality; the effects of postnatal handling; the course of the corticosterone response and behavioral measures of fear during acquisition). The present study was carried out to add pharmacological evidence to that view by testing the action of anxiogenic and anxiolytic drugs. Single 40-trial sessions with mild shocks (0.4 mA-0.6 mA) were used. In the first experiments the action of sodium pentobarbital (1.25, 2.5 and 5 mg/kg) and three benzodiazepines (diazepam, 2 and 4 mg/kg; alprazolam, 1, 1.25 and 1.5 mg/kg and adinazolam, 1, 2, 4 and 6 mg/kg) were tested. The last two experiments tested a possible proanxiety action of Ro 15-4513 (2, 5 and 10 mg/kg) and FG 7142 (5, 10 and 15 mg/kg), two partial inverse agonists of benzodiazepine receptors, which previous data had suggested to be anxiogenic. The results showed that the measure of acquisition of a two-way active avoidance is a sensitive mean for detecting either anxiolytic or anxiogenic effects of drugs, independently of their effects on locomotor activity, thus suggesting that such test could be a valid model of anxiety in animals.

Animals↗
PubMed1995

The mechanism of ion conduction by valinomycin: analysis of charge pulse responses.

Even though valinomycin has been employed and studied extensively for over 30 years, the attempts to explain its mechanism have not been entirely successful. The basic carrier model uses four rate constants that describe association of an ion and carrier, transfer of the complex across the membrane, dissociation of the complex, and transfer of the free carrier back across the membrane. If the basic model is correct all of these constants are independent of ion concentration. In previous work with rubidium the rate constants for transfer of free carrier, transfer of complexes, and dissociation were independent of the concentration, but the rate constant for association varied markedly. No satisfactory explanation for these observations was proposed. In this study current relaxations after charge pulses have been analyzed using digital data acquisition, a Bayesian algorithm, and inspection of linear plots of residuals. In agreement with previous results the relaxations for sufficiently high rubidium or potassium concentrations contain three exponential components, but the rate constants for association and dissociation decrease to similar extents as ion concentration increases. A simple extension of the carrier model to allow a more realistic description of association and dissociation is in good agreement with the rate constants fitted in the present study but not those for low ion concentrations found in previous work. At high ion concentrations the rate-limiting step in association appears to be a change in the conformation of the free carrier preceding the bimolecular association reaction. Transfer of neutral, free valinomycin between the surfaces is slower than the transfer of the charged ion-valinomycin complexes. Transfer of the complex may be hastened by deformation of the membrane, or transfer of the free carrier may be slowed by a need for conformation changes.

Algorithms↗
PubMed2000

A system for quantifying the cooling effectiveness of bicycle helmets.

This article describes the design and development of a system that is capable of quantifying the thermal comfort of bicycle helmets. The motivation for the development of the system stems from the desire both to increase helmet use and to provide the designer with a quantitative method of evaluating the thermal comfort of a helmet. The system consists of a heated mannequin head form, a heated reference sphere, a small wind tunnel, and a data acquisition system. Both the head form and the reference sphere were instrumented with thermocouples. The system is capable of simulating riding speeds ranging from 4.5-15.5 m/s. A cooling effectiveness, C1, that is independent of both ambient conditions and wind velocity is defined as a measure of how well the helmet ventilates as compared to the reference sphere. The system was validated by testing six commercially available bicycle helmets manufactured between approximately 1992 and 1998.

Analysis of Variance↗
PubMed1981

Blood velocity measurement in human conjunctival vessels.

The bulbar conjunctiva is one of the few areas in which blood flow in the peripheral vasculature can be directly and noninvasively observed in the human. Although extensive literature exists describing morphological changes which correlate with a variety of systemic diseases in this vasculature, little quantitative data is available on hemodynamics in either normal or abnormal states. The hemodynamic data available are primarily subjective assessments of "low flow." Approaches to place the subjective assessment on more quantitative grounds have usually been based on photographic techniques that have intrinsic inadequacies. The objective of the work reported here was to develop a system capable of providing sequential blood velocity data potentially useful for providing quantitative information on blood flow and its change in the microvessels of the human conjunctiva. The method that has evolved uses a standard Zeiss slit-lamp to image a subject's conjunctival vessels by using a 1-inch Newvicon TV camera with an electronic magnification of 2x. The video image is simultaneously recorded on a video tape recorder (VTR) to an overall system magnification of approximately 4 microm/raster line. The data acquisition phase requires approximately 5 minutes of patient time, whereas the actual determination of blood velocity in individual vessels is done offline through a modification of the dual-slit videodensimetric method. Two independently controllable video cursors are placed axially over the vessel image with the VTR in the still-frame mode. For each consecutive video field, the position of two reference points on the vessel and the position of each cursor relative to these and to each other are encoded into a computer to track the moving image caused by normal eye movement. The computer then determines new cursor coordinates to ensure a constant position within the vessel. The electrical signals obtained for each cursor site and for each video field are cross-correlated to yield the average blood velocity over the sampled time interval. The system has been calibrated in vitro from 0.2 to 2.5 mm/sec, evaluated in experimental animals, and used to measure blood velocity (0.3 to 1.5 mm/sec) in human conjunctival venules with diameters ranging from 20 to 50 microm. At this writing, blood velocity has been recorded during a period of about 3 months in the same vessel of several postmyocardial infarction patients. Thus, the method appears suitable for determining sequential changes in small vessel blood flow in patients over extended periods of time.

Journal Article↗
PubMed1997

The impact of nosocomial infections on patient outcomes following cardiac surgery.

STUDY OBJECTIVE: To evaluate the relationship between nosocomial infections and clinical outcomes following cardiac surgery, and to identify risk factors for the development of nosocomial infections in this patient population. DESIGN: Prospective cohort study. SETTING: Barnes-Jewish Hospital, St. Louis, a university-affiliated teaching hospital. PATIENTS: Six hundred five consecutive patients undergoing cardiac surgery. INTERVENTIONS: Prospective patient surveillance and data collection. MAIN OUTCOME MEASURES: Occurrence of nosocomial infections, multiorgan dysfunction, hospital mortality, and risk factors for the acquisition of nosocomial infections. RESULTS: One hundred thirty-one (21.7%) patients acquired at least one nosocomial infection following cardiac surgery. Four independent risk factors for the development of a nosocomial infection were identified: the duration of mechanical ventilation, postoperative empiric antibiotic administration, the duration of urinary tract catheterization, and female gender. Thirty (5.0%) patients died during their hospitalization. The mortality rate of patients acquiring a nosocomial infection (11.5%) was significantly greater than the mortality rate of patients without a nosocomial infection (3.2%) (odds ratio [OR]=4.0; 95% confidence interval [CI]=2.7 to 5.8; p<0.001). Multiorgan dysfunction was found to be the most important independent determinant of hospital mortality (adjusted OR=23.8; 95% CI=13.5 to 42.1; p<0.001) along with the aortic cross-clamp time (adjusted OR=2.3; 95% CI=1.7 to 3.0; p=0.002) and severity of illness as measured by APACHE II (acute physiology and chronic health evaluation) (adjusted OR=1.1; 95% CI=1.1 to 1.2; p=0.019). Ventilator-associated pneumonia, clinical sepsis, female gender, the cardiopulmonary bypass time, and severity of illness were identified as independent risk factors for the development of multiorgan dysfunction. Among hospital survivors, patients acquiring a nosocomial infection had longer hospital lengths of stay compared to patients without a nosocomial infection (20.1+/-13.0 days vs 9.7+/-4.5 days; p<0.001). CONCLUSIONS: Nosocomial infections, which are common following cardiac surgery, are associated with prolonged lengths of hospitalization, the development of multiorgan dysfunction, and increased hospital mortality. These data suggest potential interventions for the prevention of nosocomial infections following cardiac surgery that could substantially improve patient outcomes and decrease medical care costs.

APACHE↗
PubMed2006

Demographic predictors of circumcision status in a community-based sample of homosexual men in Sydney, Australia.

Male circumcision may reduce the risk of HIV acquisition in heterosexual men. In observational studies, confounding by demographic factors could produce spurious associations between circumcision and HIV risk. To assess this possibility, cross-sectional data on self-reported circumcision status and demographic factors were collected at baseline as part of the Health in Men study. Two-thirds of 1426 subjects were circumcised, mostly in the neonatal period. In multivariate analyses, age, ethnicity and country of birth were independently associated with circumcision status. Confounding by these demographic factors must be considered in future epidemiological studies addressing circumcision and HIV acquisition.

Adult↗
PubMed2002

Adolescents' acquisition of cigarettes through noncommercial sources.

PURPOSE: To examine the association between demographic and smoking behavior variables and the likelihood of acquiring cigarettes through noncommercial sources. The Robert Wood Johnson Foundation's 1996 National Study of Tobacco Price Sensitivity, Behavior, and Attitudes among Teenagers and Young Adults was the data source in this analysis. Respondents were high school students (grades 9 through 12) ages 13 to 19 years. The sample sizes, respondent selection procedures, and weighting procedures were designed to develop national estimates of adolescent smoking behaviors and attitudes. The questionnaire, modeled on previous surveys and input from leading tobacco control experts, was self-administered. Logistic regression was used to model the independent effects of each variable on the outcome while controlling for the influence of all other variables in the model. An inverse relationship was found between age and the likelihood of acquiring cigarettes through noncommercial sources. Females were 58% more likely to acquire cigarettes through noncommercial sources than were males. There were no differences among adolescents of different racial/ethnic groups in acquisition through noncommercial sources. Those who believed that cigarettes were difficult to acquire were more likely to obtain cigarettes by noncommercial means. Although point-of-sale restrictions have been a focal point of tobacco control legislation, these data suggest that younger smokers and those who view commercial purchase to be difficult are not using commercial sources. Therefore, more comprehensive approaches to limiting access may be required to address all sources of adolescents' acquisition. The proliferation of point-of-sale restrictions may have contributed to increases in noncommercial acquisition by creating the impression that cigarettes were more difficult to purchase. This reinforces the need for educational programs, interventions, and policies that more effectively target noncommercial sources of cigarettes.

Adolescent↗
PubMed2003

Covariance mapping in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

A novel method for acquisition and numerical analysis of matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectral data is described. The digitized ion current transient from each consecutive laser shot is first acquired and stored independently. Subsequently, statistical correlation parameters between all stored transients are computed. We illustrate the uses of this event-by-event analysis method for studies of sample surface heterogeneity as well as for elucidating the mechanisms of ion formation in MALDI. Other potential applications of the method are also outlined.

Algorithms↗
PubMed2002

[Soft copy versus hard copy findings in digital mammography].

The advantages of full field digital mammography are the excellent and reliable image quality and the reduction of radiation exposure. Image acquisition and display are decoupled in digital mammography allowing for optimization of both independently. Image displays are currently either hardcopy produced with a laser printer or softcopy using a computer monitor. Since the amount of data is high the hardware and software must meet specific technical specifications. The diagnostic accuracy of softcopy and hardcopy interpretation is comparable if a high resolution laser printer and a high quality workstation with high spatial and contrast resolution monitors are used. However, using film display the potential benefits of digital mammography in terms of manipulation of the data is lost. Additional diagnostic benefits might be gained by the combination of softcopy display and computer assisted diagnosis (CAD) and telemammography.

Breast Neoplasms↗
PubMed1984

On-line data acquisition system using an Apple computer: ISI and PST histograms.

A combined hardware/software system for the study of the temporal distributions of spike data is described. Through extensive use of assembly language subroutines the program is able to simultaneously acquire, analyze and display the incoming data. Production of a "Temporal Memory Map" makes possible the examination of acquired data at a wide variety of different bin widths. Interaction with the user is made extremely simple. Provisions are included for the labelling and printing of the output histograms and for the compact storage of data onto floppy disks. Maximum temporal resolution is 0.1 millisecond and maximum total acquisition width is 12.8 minutes. Hardware requirements beyond the basic computer consist of an external signal conditioning circuit and a slot-independent peripheral card containing two integrated circuits. The system has been successfully used in the analysis of neural and EMG evoked responses and should be widely useable in other applications.

Computers↗