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Computer graphics for slide presentations.

This applications article describes the use of a computer to generate high-quality presentation materials. Different programs and methodologies are discussed.

Computer Graphics↗

Time-scale analysis of motor unit action potentials.

Quantitative analysis in clinical electromyography (EMG) is very desirable because it allows a more standardized, sensitive and specific evaluation of the neurophysiological findings, especially for the assessment of neuromuscular disorders. Following the recent development of computer-aided EMG equipment, different methodologies in the time domain and frequency domain have been followed for quantitative analysis. In this study, the usefulness of the wavelet transform (WT), that provides a linear time-scale representation is investigated, for describing motor unit action potential (MUAP) morphology. The motivation behind the use of the WT is that it provides localized statistical measures (the scalogram) for nonstationary signal analysis. The following four WT's were investigated in analyzing a total of 800 MUAP's recorded from 12 normal subjects, 15 subjects suffering with motor neuron disease, and 13 from myopathy: Daubechies with four and 20 coefficients, Chui (CH), and Battle-Lemarie (BL). The results are summarized as follows: 1) most of the energy of the MUAP signal is distributed among a small number of well-localized (in time) WT coefficients in the region of the main spike, 2) for MUAP signals, we look to the low-frequency coefficients for capturing the average waveshape of the MUAP signal over long durations, and we look to the high-frequency coefficients for locating MUAP spike changes, 3) the Daubechies 4 wavelet, is effective in tracking the transient components of the MUAP signal, 4) the linear spline CH (semiorthogonal) wavelet provides the best MUAP signal approximation by capturing most of the energy in the lowest resolution approximation coefficients, and 5) neural network DY (DY) of Daubechies 4 and BL WT coefficients was in the region of 66%, whereas DY for the empirically determined time domain feature set was 78%. In conclusion, wavelet analysis provides a new way in describing MUAP morphology in the time-frequency plane. This method allows for the fast extraction of localized frequency components, which when combined with time domain analysis into a modular neural network decision support system enhances further the DY to 82.5% aiding the neurophysiologist in the early and accurate diagnosis of neuromuscular disorders.

Action Potentials↗

Hybrid-hybrid matrix structural refinement of a DNA three-way junction from 3D NOESY-NOESY.

Homonuclear 3D NOESY-NOESY has shown great promise for the structural refinement of large biomolecules. A computationally efficient hybrid-hybrid relaxation matrix refinement methodology, using 3D NOESY-NOESY data, was used to refine the structure of a DNA three-way junction having two unpaired bases at the branch point of the junction. The NMR data and the relaxation matrix refinement confirm that the DNA three-way junction exists in a folded conformation with two of the helical stems stacked upon each other. The third unstacked stem extends away from the junction, forming an acute angle (approximately 60 degrees) with the stacked stems. The two unpaired bases are stacked upon each other and are exposed to the solvent. Helical parameters for the bases in all three strands show slight deviations from typical values expected for right-handed B-form DNA. Inter-nucleotide imino-imino NOEs between the bases at the branch point of the junction show that the junction region is well defined. The helical stems show mobility (+/- 20 degrees) indicating dynamic processes around the junction region. The unstacked helical stem adjacent to the unpaired bases shows greater mobility compared to the other two stems. The results from this study indicate that the 3D hybrid-hybrid matrix MORASS refinement methodology, by combining the spectral dispersion of 3D NOESY-NOESY and the computational efficiency of 2D refinement programs, provides an accurate and robust means for structure determination of large biomolecules. Our results also indicate that the 3D MORASS method gives higher quality structures compared to the 2D complete relaxation matrix refinement method.

Base Pairing↗

Extended pedigree patterned covariance matrix mixed models for quantitative phenotype analysis.

Overt computational constraints in the formation of mixed models for the analysis of large extended-pedigree quantitative trait data which allow one to reliably characterize and partition sources of variation resulting from a variety sources have proven difficult to overcome. The present paper suggests that by combining a restricted patterned covariance matrix approach to modeling and partitioning the variation arising from polygenic and environmental forces with an Elston-Stewart like algorithmic approach to modeling variation resulting from a single genetic locus with large phenotypic effects one can produce a model that is at once intuitively appealing, efficient computationally, and reliable numerically. Extensions and variations of this approach are also discussed, as are some simulation and timing studies carried out in an effort to validate the accuracy and computational efficiency of the proposed methodology.

Humans↗

Is there a rational method to purify proteins? From expert systems to proteomics.

The purification of recombinant proteins for therapeutic or analytical applications requires the use of several chromatographic steps in order to achieve a high level of purity. A range of techniques is available such as anion and cation exchange chromatography, which can be carried out at different pHs, and hence used at different steps, hydrophobic interaction chromatography, gel filtration and affinity chromatography. Evidently when confronted with a complex mixture of partially unknown proteins or a clarified cell extract there are many different routes one can take in order to choose the minimum and most efficient number of purification steps to achieve a desired level of purity (e.g. 98, 99.5 or 99.9%). In this review we will show how an initial "proteomic" characterization of the complex initial mixture of target protein and protein contaminants can be used to select the most efficient chromatographic separation steps in order to achieve a maximum level of purity with a minimum number of steps. The chosen methodology was implemented in a computer based expert system. The first algorithm developed was used to select the most efficient purification method to separate a protein from its contaminants based on the physicochemical properties of the protein product and the protein contaminants. The second algorithm developed was used to predict the number and concentration of contaminants after each separation as well as protein product purity. The successful application of the expert system approach, based on an initial proteomic characterization, to the practical cases of protein mixtures and clarified fermentation supernatant is presented and discussed. The purification strategy proposed was experimentally tested and validated with a mixture of four proteins and the experimental validation was also carried out with an "unknown" supernatant of Bacillus subtilis producing a recombinant beta-1,3-glucanase. The system was robust to errors <10% which is the range that can be found in the experimental determination of the properties in the database of product and contaminants. On the other hand, the system was sensitive both to larger variations (>20%) in the properties of the contaminant database and the protein product and to variations in one protein property (e.g. hydrophobicity).

Animals↗

Static curvature and flexibility measurements of DNA with microscopy. A simple renormalization method, its assessment by experiment and simulation.

We present the derivation of equations based on statistical polymer chain analysis and a method to quantify the average angle value of intrinsic bends and the local flexibility at a given locus on DNA fragments imaged by electron microscopy. DNA fragments of n base-pairs are considered as stiff chains of n jointed unit rigid rods. If the DNA fragments are composed of two branches A0Am and A0Bn, with, respectively, m and n base-pairs, where the standard deviations of the angle formed by two consecutive base-pairs are uniform over each branch, respectively, sigmathetaA and sigmathetaB, we show that the standard deviation of the angle AmA0Bn is: [formula: see text] where sigmatheta0 is the standard deviation of the angle at locus A0. This equation is established for small angular deviations by analysis of DNA at different scales and the validity of the methodology is controlled with the computation of the reduced chi2 statistical test. The length of the DNA fragments must be of the order of, or below, the persistence length, as determined by sets of statistics from computer simulations of DNA fragments. This is verified experimentally by a detailed analysis of the digitized contours of homogeneous linear 139 base-pair DNA fragments observed by electron microscopy. The images are compared to the reconstruction of DNA fragments from the measurements. The value found, sigma0=4.6 degrees/bp, is consistent with the well-accepted value for DNA in a plane. We discuss the relationship between the standard deviation of the measured angles and the flexibility at the base-pair level. This method is useful to quantify directly from microscopy techniques, such as electron or scanning force microscopy, the true bending angle, either intrinsic or induced by a ligand, and its associated flexibility at a given locus in any small DNA fragment.

Base Pairing↗

Proteome mapping by two-dimensional polyacrylamide gel electrophoresis in combination with mass spectrometric protein sequence analysis.

The high resolving power of two-dimensional polyacrylamide gel electrophoresis 2D-PAGE and its full analytical and preparative potential have been described with special emphasis on reproducibility and standardization of protein spot patterns, enhanced protein detection sensitivity, and computer analysis database development. New methodologies for peptide mass fingerprinting, peptide, sequence, and fragmentation tagging have been highlighted. Major challenges associated with 2D-PAGE/mass spectrometric protein sequencing were outlined which need to be addressed in the future, including sample enrichment, use of alternative gel matrices, improvements in separation systems interfaced directly to the mass spectrometer, and design of high-sensitivity instruments with very high mass ranges. It is hoped that comparative studies to identify, quantitate, and characterize proteins differentially expressed in normal versus diseased cells would give insight into mechanisms of pathogenesis and allow the development of a way to control both the etiology and the course of diseases.

Electrophoresis, Polyacrylamide Gel↗

Quantitative structure-agonist activity relationship of capsaicin analogues.

The MULTIple Computer Automated Structure Evaluation (MULTICASE) methodology has been used to study the quantitative structure-agonist activity relationship of a series of capsaicin agonists. A number of substructures and physiochemical properties of capsaicin analogues were identified as being responsible for high agonist potency. The optimal log P value for the agonist potency as estimated from QSAR analysis is 5.12. It was also found that a cluster of inactive molecules in the database have lipophilicity values below 2.94. Molecular modeling was employed to elucidate the detailed structural features of the pharmacophore of capsaicin analogues. Systematic conformational analysis has shown that the activity of capsaicin analogues strongly depends upon their ability to reach the required conformational profile. Based upon these observations, a three-dimensional pharmacophore model for the capsaicin-receptor interactions is proposed.

Capsaicin↗

A dynamic numerical method for models of renal tubules.

We show that an explicit method for solving hyperbolic partial differential equations can be applied to a model of a renal tubule to obtain both dynamic and steady-state solutions. Appropriate implementation of this method eliminates numerical instability arising from reversal of intratubular flow direction. To obtain second-order convergence in space and time, we employ the recently developed ENO (Essentially Non-Oscillatory) methodology. We present examples of computed flows and concentration profiles in representative model contexts. Finally, we indicate briefly how model tubules may be coupled to construct large-scale simulations of the renal counterflow system.

Body Water↗

How to teach evidence-based surgery.

The objectives of teaching evidence-based surgery (EBS) are to inform and convince that EBS is a method of interrogation, reasoning, appraisal, and application of information to guide physicians in their decisions to best treat their patients. Asking the right, answerable questions, translating them into effective searches for the best evidence, critically appraising evidence for its validity and importance, and then integrating EBS with their patients' values and preferences are daily chores for all surgeons. Teaching and learning EBS should be patient-centered, learner-centered, and active and interactive. The teacher should be a model for students to become an expert clinician who is able to match and take advantage of the clinical setting and circumstances to ask and to answer appropriate questions. The process is multistaged. Teaching EBS in small groups is ideal. However, it is time-consuming for the faculty and must be clearly and formally structured. As well, evidence-based medicine (EBM) courses must cater to local institutional needs, must receive broad support from the instructors and the providers of information (librarians and computer science faculty), use proven methodologies, and avoid scheduling conflicts. In agreement with others, we believe that the ideal moment to introduce the concepts of EBM into the curriculum of the medical student is early, during the first years of medical school. Afterward, it should be continued every year. When this is not the case, as in many countries, it becomes the province of the surgeon in teaching hospitals, whether they are at the university, are university-affiliated, or not, to fulfill this role.

Decision Making↗

Fine-resolution mapping of wildfire fuel types for Canada: Fuzzy logic modeling for an Alberta pilot area.

The Canadian Forest Fire Danger Rating System (CFFDRS) is used daily across Canada for evaluating forest fire danger. Fuel-type information is one of the inputs required by the models used in the CFFDRS. In this project, three fuel-type maps with a 25 m resolution were produced for a pilot study area located in Alberta using land cover only; land cover and biomass; and, land cover, biomass and leaf area index data derived from satellite imagery. The relationships between inputs and fuel types were determined mainly by the opinions of forest fire scientists and incorporated into a computer program using fuzzy set methodology. Not all the CFFDRS fuel types could be distinguished using these inputs; three of the coniferous types had to be grouped into one common fuel type. Overall accuracy was between 74 and 83% based on ground-truth comparisons. The most accurate map resulted from land cover and biomass data. Detailed accuracy assessment indicated that the overall accuracy increased up to 86% if ambiguous fuel type identification was considered. No combination of inputs was able to define a fuel type with absolute certainty, which is a reflection of differing expert opinions and the small number of inputs used to produce the maps.

Alberta↗

Current technologies in the evaluation of bone architecture.

In the context of osteoporosis, bone quality (which encompasses trabecular bone and cortical bone architecture), bone mineralization, turnover, and microdamage are all important, as are bone density and total content. Noninvasive assessment of bone quality has recently received considerable attention because bone density alone is not a surrogate for fracture prevalence and occurrence, and does not completely explain the therapeutic efficacy of emerging treatments. This paper focuses on the assessment of trabecular bone architecture, one of the factors that governs bone strength and may be categorized as a contributor to bone quality. The methodologies described include micro-computed tomography, magnetic resonance imaging, and computerized analysis of radiographic patterns of trabecular bone.

Bone Density↗

Integrating ethics in design through the value-sensitive design approach.

The Accreditation Board of Engineering and Technology (ABET) has declared that to achieve accredited status, 'engineering programs must demonstrate that their graduates have an understanding of professional and ethical responsibility.' Many engineering professors struggle to integrate this required ethics instruction in technical classes and projects because of the lack of a formalized ethics-in-design approach. However, one methodology developed in human-computer interaction research, the Value-Sensitive Design approach, can serve as an engineering education tool which bridges the gap between design and ethics for many engineering disciplines. The three major components of Value-Sensitive Design, conceptual, technical, and empirical, exemplified through a case study which focuses on the development of a command and control supervisory interface for a military cruise missile.

Automation↗

Does hypnotizability modulate the stress-related endothelial dysfunction?

Previous studies suggest that hypnotizability represents a protective factor against the cardiac effects of cognitive stress and that hypnosis prevents vascular stress-induced modifications in highly hypnotizable individuals. The aim of the experiment was to investigate whether a similar effect at vascular level is present in awake subjects with a high (Highs) and a low (Lows) hypnotic susceptibility. Thus, brachial artery post-ischaemic flow-mediated vascular dilation (FMD) was evaluated non-invasively by ultrasound methodology during cognitive stress (mental computation) in Highs and Lows. Results showed that Highs, similarly to that previously observed in hypnotized Highs and in contrast with Lows, did not exhibit any stress-related endothelial dysfunction (FMD decrement). Thus, hypnotizability should be considered a protective factor against vascular disease.

Adult↗

Distress about sex: a national survey of women in heterosexual relationships.

As a consequence of the impact of Viagra on male sexual dysfunction, considerable attention is now being paid to sexual dysfunctions in women, which might respond to pharmacological treatment. Should women's sexual problems be conceptualized in the same way as men's? The objective of this study was to assess the prevalence of distress about sexuality among women, and examine the predictors of such distress, including aspects of the woman's sexual experience, as well as other aspects of hercurrent situation. A telephone survey of women used Computer Assisted Telephone Interviewing and Telephone-Audio-Computer-Assisted Self-Interviewing methodology to investigate respondents' sexual experiences in the previous month. A national probability sample was used of 987 White or Black/African American women aged 20-65 years, with English as first language, living for at least 6 months in a heterosexual relationship. The participation rate was 53.1%. Weighting was applied to increase the representativeness of the sample. A total of 24.4% of women reported marked distress about their sexual relationship and/or their own sexuality. The best predictors of sexual distress were markers of general emotional well-being and emotional relationship with the partner during sexual activity. Physical aspects of sexual response in women, including arousal, vaginal lubrication, and orgasm, were poor predictors. In general, the predictors of distress about sex did not fit well with the DSM-IV criteria for the diagnosis of sexual dysfunction in women. These findings are compared with those from other studies involving representative samples of women, and the conceptual issues involved in the use of terms such as "sexual problem" and "sexual dysfunction" are discussed.

Adult↗

Attention training in the cognitive rehabilitation of schizophrenic patients: a review of efficacy studies.

OBJECTIVE: To review the literature on effects of attention and cognitive training on attentional functioning in schizophrenic patients. METHOD: Relevant efficacy studies were identified by literature searches (in Medline, Current Contents, Psyclit, and Psyndex databases) and through the reference lists of key papers. RESULTS: Re-examination of findings from nine methodologically adequate studies using computer-based or non-computer-based training procedures provided inconsistent results. On 16 of 35 outcome measures significant performance improvements were observed from pre-treatment to post-treatment but on the majority of the applied measures no performance improvement could be determined. In general, treatment effect sizes but also power of tests were low. For nearly all the outcome measures for which differential training effects were reported there also exist contradictory outcome results. CONCLUSION: There is inconclusive evidence that attention training is effective in schizophrenia. Longitudinal efficacy studies are needed in which different aspects of attention are systematically exercised and assessed.

Attention↗

Theoretical modeling of the valence UV spectra of 1,2,3-triazine and uracil in solution.

Assessment of the perturbed matrix method (PMM) ability in reproducing valence UV absorption spectra is carried out on two model systems: 1,2,3-triazine in methanol solution and uracil in water solution. Results show that even using the simplest definition of the quantum center, i.e. the portion of the system explicitly treated quantum mechanically, PMM provides rather good results. This paper further confirms the possibility of using PMM as a theoretical-computational tool, complementary to other methodologies, for addressing the electronic properties in molecular systems of high complexity.

Mathematics↗

Dynamic torque and apical forces of ProFile.04 rotary instruments during preparation of curved canals.

AIM: To analyse torque and force generated whilst shaping curved canals using rotary instruments. METHODOLOGY: A specially designed computer-controlled testing platform was used to record events during the shaping of straight and curved canals in plastic blocks and in extracted human teeth using ProFile.04 instruments. Size 40 apical stops were prepared using crown-down, apical preparation and step-back procedures. Maximum torque, apically directed force and the numbers of revolutions were recorded at a resolution of 100 samples s-1. Load causing separation as required by the ISO 3630-1 test and cyclic fatigue was also recorded. Mean maximum scores were calculated and statistically tested using one- and two-way analyses of variance. RESULTS: Highest and lowest torque scores were recorded, respectively, in straight canals in plastic blocks at 25 Nmm and in natural canals at 14 Nmm. Significant differences were recorded for canal type and preparation phase (P < 0.0001). Loads causing separation varied from 3.7 to 32.3 Nmm. Apically directed forces ranged from 1 to 7.5 N. Again, there were significant differences depending on canal type and preparation phase (P < 0.0001). The number of revolutions during preparation ranged from 18 to 41. Size 15, 30 and 45 ProFile.04 instruments separated after 581, 430 and 402 revolutions, respectively, in a standard cyclic fatigue test. CONCLUSIONS: The new torque-testing platform details physical parameters during preparation of curved canals. To improve predictability, instrumentation sequences must be tested for excessively high torsional moments or forces. This study indicated that up to 10 curved canals could be safely prepared with a sequence of ProFile. 04 rotary instruments without separation due to cyclic fatigue. Efforts should continue to correlate root canal anatomy with torque and force generated during rotary root canal preparation.

Analysis of Variance↗