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ESCA studies of surface chemical composition of segmented polyurethanes.

Surface chemical analysis of two commercially available polyurethanes, i.e., Avcothane and Biomer was carried out by electron spectroscopy for chemical analysis (ESCA). The depth which is subject to analysis is in the range of 50-100 A. The variables studied in this study are the difference in exposure to air or to the mold substrate during the solvent casting process. Model compounds such as a pure polydimethylsiloxane, polyether soft segment and hard segment copolymer were used to identify and assign various ESCA peaks. The air facing surface of Avcothane which is the blood contacting surface is found to be covered mostly with polydimethylsiloxane polymer, with a small amount of polyether soft segment mixed with silicone. Therefore, the hard segment of the polyurethanes is hidden beneath the blood contact surface in Avcothane. In Biomer films, the air facing surface contains a greater concentration of polyether soft segment than the substrate surface. These results are consistent with our previous results obtained by Fourier transform IR internal reflection and Auger electron spectroscopy.

Carbon↗

Ploidy level variability in South American fescues (festuca L., poaceae): use of flow cytometry in up to 5 1/2-year-old caryopses and herbarium specimens.

Ploidy levels and chromosome numbers for 24 species of Festuca L. from 29 sites in Bolivia, Colombia, Ecuador and Venezuela are given. The ploidy level of 22 species is reported for the first time. A higher proportion of tetraploids in northern South America and the high frequency of polyploids in the whole continent are documented. In combination with chromosome counts, ploidy level was determined using flow cytometry in 4- to 5 1/2 -year-old herbarium specimens and mature caryopses. Flow cytometric determination from seeds was more reliable than determination from herbarium specimens. In herbarium specimens, the youngest, fresh green leaves, still hidden in sheaths, seem to be most suitable for cytometric determination. In old, brownish leaves, or poorly preserved herbarium specimens, the degradation of DNA signal in flow histograms was documented. DNA content measured in seeds was always higher than that measured in herbarium specimens, which may be caused by the presence of different cytosolic compounds. Differences of about 15% in relative DNA content of F. sodiroana and F. vaginalis was found in simultaneous measurements in seeds.

DNA, Plant↗

On hidden heterogeneity in directional asymmetry--can systematic bias be avoided?

Directional asymmetry (DA) biases the analysis of fluctuating asymmetry (FA) mainly because among-individual differences in the predisposition for DA are difficult to detect. However, we argue that systematic bias mainly results from predictable associations between signed right-left asymmetry and other factors, i.e. from systematic variation in DA. We here demonstrate methods to test and correct for this, by analysing bilateral asymmetry in size and shape of an irregular sea urchin. Notably, in this model system, DA depended significantly on body length and geographic origin, although mean signed asymmetry (mean DA) was not significant in the sample as a whole. In contrast to the systematic variation in DA, undetectable, random variability in the underlying DA mainly leads to reduced statistical power. Using computer simulations, we show that this loss of power is probably slight in most circumstances. We recommend future studies on FA to routinely test and correct for not only as yet for mean DA, but also for systematic variation in DA.

Analysis of Variance↗

Genetic variation in Cameroon: thermostability variants of hemoglobin and of glucose-6-phosphate dehydrogenase.

The technique of heat denaturation was used in addition to electrophoresis for the detection of thermostability variants of hemoglobin and glucose-6-phosphate dehydrogenase in an attempt to measure the amount of genetic variability present in villages in the United Republic of Cameroon, Equatorial Africa. A minimum of three to a maximum of 13 thermostability variants were estimated for HbA and HbS, and a minimum of two to a maximum of ten thermostability variants were estimated for GdA, GdB, and GdA-. It is suggested that hemoglobin and glucose-6-phosphate dehydrogenase thermostability variants are genetically determined and that the sites of these variants are at the hemoglobin and glucose-6-phosphate dehydrogenase structural loci. The evidence for the existence of these hidden variants and their importance in the neutralist v. selectionist controversy are discussed.

Cameroon↗

Molecular similarity analysis and virtual screening by mapping of consensus positions in binary-transformed chemical descriptor spaces with variable dimensionality.

A novel compound classification algorithm is described that operates in binary molecular descriptor spaces and groups active compounds together in a computationally highly efficient manner. The method involves the transformation of continuous descriptor value ranges into a binary format, subsequent definition of simplified descriptor spaces, identification of consensus positions of specific compound sets in these spaces, and iterative adjustments of the dimensionality of the descriptor spaces in order to discriminate compounds sharing similar activity from others. We term this approach Dynamic Mapping of Consensus positions (DMC) because the definition of reference spaces is tuned toward specific compound classes and their dimensionality is increased as the analysis proceeds. When applied to virtual screening, sets of bait compounds are added to a large screening database to identify hidden active molecules. In these calculations, molecules that map to consensus positions after elimination of most of the database compounds are considered hit candidates. In a benchmark study on five biological activity classes, hits for randomly assembled sets of bait molecules were correctly identified in 95% of virtual screening calculations in a source database containing more than 1.3 million molecules, thus providing a measure of the sensitivity of the DMC technique.

Journal Article↗

Design and test of neural networks and statistical classifiers in computer-aided movement analysis: a case study on gait analysis.

OBJECTIVE: To describe the methods for designing and testing diagnostic systems in movement analysis and to verify the clinical usefulness of neural networks and statistical classifiers in a case study. DESIGN: Connectionist and statistical models trained and tested with measured data. BACKGROUND: A basic need in rehabilitation and related fields is to efficiently manage the vast information obtained from a movement analysis laboratory. Many studies have dealt with the interpretation of measured variables in order to correlate objective descriptors to the presence and/or severity of specific neuromusculoskeletal disorders or their consequences. This traditional analytical approach has been complemented in the last decade by new non-linear classification tools called neural networks. METHODS: A gait analysis study on 148 lower limb arthrosis patients and 88 age-matched control subjects. Pathological and healthy gait patterns obtained from force plates wer discriminated by means of multilayer perceptrons and statistical classifiers. RESULTS: Ten input features were enough to train a multilayer perceptron with six hidden neurons. The discrimination rate of the neural net was 80% after cross-validation, significantly higher (P<0.05) than the performance of a Bayes quadratic classifier (about 75%). A great variance due to a small cross-validation set could be demonstrated. CONCLUSIONS: Strict statistical requirements must be observed for designing a neural network. Although these models attain a better performance than conventional statistical approaches, the benefits they bring are sometimes not sufficient to justify their use. Furthermore, clinicians routinely involved in critical decisions may not consider such diagnostic systems reliable enough.

Journal Article↗

Tumor feature visualization with unsupervised learning.

Dynamic contrast enhanced magnetic resonance imaging (DCE MRI) is applied for diagnosis and therapy control of breast cancer. The malignancy of a lesion is expressed in the average signal kinetics of selected regions of interest (ROI) representing the lesion. The technique is reported to characterize malignant tumors with high sensitivity and highly variable specificity. Computer-based diagnosis (CAD) systems have been proposed to analyze and classify signal time curve data, extracted from hand selected ROI in the DCE MRI data. In this paper, we apply the self-organizing map (SOM) to a set of time curve feature vectors of single voxels from seven benign lesions and seven malignant tumors. Applying the SOM we are able to project the time curve values of each voxel on a two-dimensional map. The results show, that the SOM is able to visualize the hidden two-dimensional structure of the six-dimensional signal space. Using the trained SOM, we are able to identify voxels with benign or malignant signal characteristics and to visualize lesion cross-sections with pseudo-colors. A comparison with the established three time points method shows that the SOM has clear potential for deriving visualization parameters in DCE MRI analysis.

Breast Neoplasms↗

First application of the SINE (short interspersed repetitive element) method to infer phylogenetic relationships in reptiles: an example from the turtle superfamily Testudinoidea.

Although turtles (order Testudines) constitute one of the major reptile groups, their phylogenetic relationships remain largely unresolved. Hence, we attempted to elucidate their phylogeny using the SINE (short interspersed repetitive element) method, in which the sharing of a SINE at orthologous loci is indicative of synapomorphy. First, a detailed characterization of the tortoise polIII/SINE was conducted using 10 species from eight families of hidden-necked turtles (suborder Cryptodira). Our analysis of 382 SINE sequences newly isolated in the present study revealed two subgroups, namely Cry I and Cry II, which were distinguishable according to diagnostic nucleotides in the 3' region. Furthermore, four (IA-ID) and five (IIA-IIE) different SINE types were identified within Cry I and Cry II subgroups, respectively, based on features of insertions/deletions located in the middle of the SINE sequences. The relative frequency of occurrence of the subgroups and the types of SINEs in this family were highly variable among different lineages of turtles, suggesting active differential retroposition in each lineage. Further application of the SINE method using the most retrotranspositionally active types, namely IB and IC, challenged the established phylogenetic relationships of Bataguridae and its related families. The data for 11 orthologous loci demonstrated a close relationship between Bataguridae and Testudinidae, as well as the presence of the three clades within Bataguridae. Although the SINE method has been used to infer the phylogenies of a number of vertebrate groups, it has never been applied to reptiles. The present study represents the first application of this method to a phylogenetic analysis of this class of vertebrates, and it provides detailed information on the SINE subgroups and types. This information may be applied to the phylogenetic resolution of relevant turtle lineages.

Amino Acid Sequence↗

Attachment-related strategies during thought suppression: ironic rebounds and vulnerable self-representations.

The authors conducted 2 studies of attachment-related variations in thought suppression. Participants were asked, or not asked, to suppress thoughts about a relationship breakup and then to perform a Stroop task under high or low cognitive load. The dependent variables were the rebound, of previously suppressed separation-related thoughts (Study 1) and the accessibility of self-traits (Study 2). Under low cognitive load, avoidant individuals did not show any rebound of separation-related thoughts and activated positive self-representations. Under high cognitive load, avoidant participants failed to suppress thoughts of separation and were more likely to activate negative self-representations. Attachment anxiety was associated with high activation of negative self-representations and unremitting separation-related thoughts. The results are discussed in terms of the hidden vulnerabilities of avoidant individuals.

Adult↗

Innocent and less-innocent solvent ligands: a systematic investigation of cationic iron chloride/alcohol complexes by electrospray ionization mass spectrometry complemented by DFT calculations.

The influence of anionic and neutral ligands on the reactivity of cationic iron complexes towards methanol, ethanol, and iso- and n-propanol has been investigated by means of electrospray ionization (ESI) mass spectrometry, and in key questions the experimental results are supported by DFT calculations. The chemical processes taking place when FeCl2+ is coordinated to a variable number of alcohol molecules were investigated by collision experiments, as well as reactivity and labeling studies. The most abundant cations formed upon ESI of FeCl3/ROH mixtures can be described as consisting of a covalently bound FeCl2+ core, which is stabilized by neutral ROH ligands, for example, FeCl2(CH3OH)n+. Indications for a hydrogen-bonding mechanism of ligands in the second coordination sphere are given by the observation of the formally hypercoordinated ion FeCl2(CH3OH)5+ and interpretation of kinetic data for n=4. Further, deuterium labeling experiments disclose a number of hidden hydrogen transfers and imply that complexes with n=1 and 2 can exist in two tautomeric forms. Upon change of the alcohol ligand from methanol to ethanol and propanol, additional reaction pathways become accessible, among which metal-assisted dehydration of the respective alcohols by means of an ion/dipole mechanism is the most important.

Journal Article↗

Feasibility of estimating isokinetic knee torque using a neural network model.

Many studies have investigated the relationships between electromyography (EMG) and torque production. A few investigators have used adjusted learning algorithms and feed-forward artificial neural networks (ANNs) to estimate joint torque in the elbow. This study sought to estimate net isokinetic knee torque using ANN models. Isokinetic knee extensor and flexor torque data were measured simultaneously with agonist and antagonist EMG during concentric and eccentric contractions at joint velocities of 30 degrees /s and 60 degrees /s. Age, gender, height, body mass, agonist EMG, antagonist EMG, joint position and joint velocity were entered as predictive variables of net torque. A three-layer ANN model was developed and trained using an adjusted back-propagation algorithm. Accuracy results were compared against those of forward stepwise regression models. Stepwise regression models included body mass, body height and joint position as the most influential predictors, followed by agonist EMG for concentric and eccentric contractions. Estimation of eccentric torque included antagonist EMG following the agonist activation. ANN models resulted in more accurate torque estimation (R=0.96), compared to the stepwise regression models (R=0.71). ANN model accuracy increased greatly when the number of hidden units increased from 5 to 10, continuing to increase gradually with additional hidden units. The average number of training epochs necessary for solution convergence and the relative accuracy of the model indicate a strong ability for the ANN model to generalize these estimations to a broader sample. The ANN model appears to be a feasible technique for estimating joint torque in the knee.

Adult↗

Age differences in attributions to causality: implications for intellectual assessment.

Negative attributions and failure expectations held by elderly test-takers may be confounding ability-extraneous variables and thus may contribute to lowered intellectual performance. The present study, using the contextualistic model, examined these confounds through experimental manipulation of causal attributions to test outcome in younger and older individuals. Eighty females (40 elderly; 40 younger) were exposed to noncontingent failure (unsolvable test items) and received a verbal massage stating their failure and relating it to either their ability, effort, or no cause. A fourth group exposed to identical failure was not given feedback. Subjects in all four groups for both ages were then administered three solvable intelligence sub-tests: Reasoning, Hidden Patterns, and Paper Folding. Older subjects exhibited significantly lower success expectations and performed more poorly on all three tests. Also, older and younger subjects, in the absence of suggested causal ascription, showed differential performance in the Paper Folding Test. Younger subjects with no experimenter-given cause for failure exhibited facilitation of performance while older subjects' performances, under the same conditions, showed deficits. Results are discussed in reference to attributional style research and the contextualistic viewpoint.

Adolescent↗

Schisis-like rhegmatogenous retinal detachment associated with choroidal colobomas.

BACKGROUND: The breaks that cause retinal detachments in colobomatous eyes are often hidden within the lesion and difficult to find. METHOD: To elucidate the pathoanatomy and possible pathomechanism of such detachments, histological sections of eight choroidal colobomas were reviewed. RESULTS: Sections of the margin showed central continuation of the inner neuroblastic layer (the intercalary membrane) and eversion and separation of the outer neuroblastic layer. The opposite direction of continuity of the neuroblastic layers created a schisis-like configuration between the intercalary membrane and the everted outer retina. The zone of duplication was a point of retinal adhesion, but also a locus minoris resistentiae due to vitreous attachments and variable glial support at the margin. CONCLUSION: The subset of coloboma-associated retinal detachments requires both a central break in the inner layer and a break in the outer layer at the margin of the coloboma. The inner layer break may be precipitated by retinovascular ischemia or scleral stretching; that in the outer layer may be caused by vitreous traction on the margin of the coloboma or extension of the formerly isolated detachment through the outer marginal zone of decreased glial support.

Child, Preschool↗

Neural network analysis in pharmacogenetics of mood disorders.

BACKGROUND: The increasing number of available genotypes for genetic studies in humans requires more advanced techniques of analysis. We previously reported significant univariate associations between gene polymorphisms and antidepressant response in mood disorders. However the combined analysis of multiple gene polymorphisms and clinical variables requires the use of non linear methods. METHODS: In the present study we tested a neural network strategy for a combined analysis of two gene polymorphisms. A Multi Layer Perceptron model showed the best performance and was therefore selected over the other networks. One hundred and twenty one depressed inpatients treated with fluvoxamine in the context of previously reported pharmacogenetic studies were included. The polymorphism in the transcriptional control region upstream of the 5HTT coding sequence (SERTPR) and in the Tryptophan Hydroxylase (TPH) gene were analysed simultaneously. RESULTS: A multi layer perceptron network composed by 1 hidden layer with 7 nodes was chosen. 77.5 % of responders and 51.2% of non responders were correctly classified (ROC area = 0.731--empirical p value = 0.0082). Finally, we performed a comparison with traditional techniques. A discriminant function analysis correctly classified 34.1 % of responders and 68.1 % of non responders (F = 8.16 p = 0.0005). CONCLUSIONS: Overall, our findings suggest that neural networks may be a valid technique for the analysis of gene polymorphisms in pharmacogenetic studies. The complex interactions modelled through NN may be eventually applied at the clinical level for the individualized therapy.

5' Untranslated Regions↗

Interpreting oscillations of muscle sympathetic nerve activity and heart rate variability.

Computer analysis of spontaneous cardiovascular beat-by-beat variability has gained wide credibility as a means of inferring disturbances of autonomic cardiovascular regulation in a variety of cardiovascular conditions, including hypertension, myocardial infarction and heart failure. Recent applications of spectral analysis to muscle sympathetic nerve activity (MSNA) offer a new approach to a better understanding of the relationship between cardiovascular oscillations and autonomic regulation. However, areas of uncertainty and unresolved debates remain, mostly concerning different methodologies and interpretative models that we will consider in this article. Perusal of all available literature suggests that average sympathetic nerve activity and its oscillatory components, although correlated to some extent, are likely to provide different types of information. In addition, the specific experimental context is of paramount importance, as the rules that seem to govern the relationship between average and oscillatory properties of MSNA appear to be different in usual conditions and in conditions of extremes of activation or disease. In general, dynamic experiments, such as with graded tilt or with vasoactive drugs, are more suited to investigations of the complexity of autonomic regulation than are static comparisons. In addition, because the information is spread across variables and is affected by a potentially large error, it appears that several different techniques should be perceived as complementary rather than as mutually exclusive. Available evidence suggests that low-frequency and high-frequency oscillations in peripheral signals of variability might have a predominantly central, rather than a peripheral, origin and that this applies in particular to low-frequency oscillations. A crucial point in the assessment of the meaning of spectral components relates to consideration of the varying level of very-low-frequency noise, and the mathematical manipulation of derived indices, particularly using a normalization procedure. This appears easier to obtain with auto-regressive than with fast Fourier techniques. With this approach, discrepant interpretations seem to be resolved, provided adequate care is taken in separating direct physiological data from derived meaning, which relates to hidden information and neural codes; in the case of sympathetic discharge, the latter display greater complexity than simple average spike activity per unit time. Accordingly we believe, in conclusion, that the judicious use of spectral methodology, in addition to other techniques, might provide unprecedented, useful insights into autonomic cardiovascular regulation, in both physiopathological and clinical circumstances.

Animals↗

Childhood residential mobility and multiple health risks during adolescence and adulthood: the hidden role of adverse childhood experiences.

BACKGROUND: Throughout US history, US society has been characterized by its high degree of residential mobility. Previous data suggest a relationship between mobility and increased health risk, but this relationship might be confounded by unmeasured adverse childhood experiences (ACEs). OBJECTIVES: To examine the relationship of childhood residential mobility to health problems during adolescence and adulthood and to determine how much these apparent relationships may result from underlying ACEs. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 8116 adults who completed a survey that included childhood residential mobility, ACEs (childhood abuse, childhood neglect, and household dysfunction), and multiple health problems. MAIN OUTCOME MEASURES: Number of childhood residential moves and number of ACEs (ACE score) were assessed for relationships to depressed affect, attempted suicide, alcoholism, smoking, early sexual initiation, and teenaged pregnancy. RESULTS: After adjustment for demographic variables, the risk of high residential mobility during childhood (> or = 8 moves) was 1.7- to 3.1-fold for each ACE, and increased with the number of ACEs. Compared with respondents who never moved, the odds of health risk for respondents with high mobility during childhood ranged from 1.3 (for smoking) to 2.5 (for suicide). However, when the number of ACEs was entered into multivariate models, the relationship between mobility and health problems was greatly reduced. CONCLUSIONS: Adverse childhood experiences are strongly associated with frequent residential mobility. Moreover, the apparent relationship between childhood mobility and various health risks is largely explained by ACEs. Thus, previous studies showing a relationship between residential mobility and negative outcomes were likely confounded by unmeasured ACEs.

Adolescent↗

Hidden Markov models for settings with interval-censored transition times and uncertain time origin: application to HIV genetic analyses.

The simplicity and flexibility of Markov models make them appealing for investigations of the acquisition of HIV drug-resistance mutations, whose presence can define specific Markov states. Because the exact time of acquiring a mutation is not observed during clinical research studies on HIV infection, it is important that methods for fitting such models accommodate interval-censored transition times. Furthermore, many such studies include patients with extensive treatment experience prior to the onset of the studies. Therefore, the virus in these patients may have already acquired resistance mutations by study entry. Retrospective data regarding the time on treatment, which is often known or known with error, provide information about the acquisition rates before the start of a study. Finally, variability in the genetic sequences of circulating HIV creates uncertainty in the Markov states. This paper considers approaches to fitting Markov models to data with interval-censored transition times when the time origin and the Markov states are known with error. The methods were applied to AIDS Clinical Trial Group protocol 398, a randomized comparison of mono- versus dual-protease inhibitor use in heavily pretreated patients. We found that the estimated rates of acquiring certain classes of mutations depended on the presence of others, and that the precision of these estimates can be considerably improved by inclusion of retrospective data.

Drug Resistance, Multiple, Viral↗

Receptor co-operation in retrovirus entry: recruitment of an auxiliary entry mechanism after retargeted binding.

We have constructed Moloney murine leukemia virus (MoMLV)-derived envelope glycoproteins (AMO) displaying an amino-terminal Ram-1-binding domain in which a variety of different amino acid spacers have been inserted between the displayed domain and the MoMLV surface (SU) subunit. Titres of retroviruses generated with these chimeric envelopes were enhanced on cells expressing both Ram-1 and Rec-1 receptors compared with the titres on cells expressing only one or other receptor type. The absolute viral titres and the degree of titre enhancement due to receptor cooperativity were highly variable between the different chimeric envelopes and were determined primarily by the properties of the interdomain spacer. An extreme example of receptor co-operativity was encountered when testing Ram-1-targeted AMOPRO envelopes with specific proline-rich interdomain spacers. AMOPRO viruses could not enter cells expressing only Rec-1 or only Ram-1 but could efficiently infect cells co-expressing both receptors. The data are consistent with a model for receptor co-operativity in which binding to the targeted (Ram-1) receptor triggers conformational rearrangements of the envelope that lead to complete unmasking of the hidden Rec-1-binding domain, thereby facilitating its interaction with the viral (Rec-1) receptor which leads to optimal fusion triggering.

3T3 Cells↗