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Further argument for the existence of a pacemaker in the human information processing system.

To support the idea that temporal information processing may depend on an internal clock, Treisman et al. proposed a pacemaker model (Treisman, M., Faulkner, A., Naish, P.L.N., Brogan, D., 1990. The internal clock: Evidence for a temporal oscillator underlying time perception with some estimates of its characteristics frequency. Perception 19, 705-743.) and a technique for interfering with it by introducing an external periodic phenomenon. Experimental results obtained by these authors on time estimation and production tasks support this model. In another study, Treisman et al. established that the pacemaker also affects reaction times (RT) (Treisman, M., Faulkner, A., Naish, P.L.N., 1992. On the relation between time perception and the timing of motor action: Evidence for a temporal oscillator controlling the timing of movement. Quarterly Journal of Experimental Psychology 45A, 235-263.). In the present study, we addressed the question as to which information processing stage (Sanders, A.F., 1980. Stage analysis of reaction process, In: Stelmach, G.E., Requin, J. (Eds.). Tutorials in motor behavior. North-Holland, Amsterdam, pp. 331-354.) is affected by this internal clock. For this purpose, we used the Additive Factors Method (Sternberg, S., 1969. The discovery of processing stages: Extension of Donder's method. In: Koster, W.G. (Ed.). Attention and Performance II. Acta Psychologica 30, 276-315.). To vary sensorial processing time, we used two visual stimulus intensities. Stimulus-response mapping was manipulated to enhance central processing time. To modify the duration of the motor stages, the two responses could be given by two fingers on the same hand (right ring vs. middle finger) or by two fingers of the different hands (right ring vs. left middle finger). Intensity of the stimulus, stimulus-response mapping, and repertoire of responses were found to be additive. We obtained RT modulations similar to those obtained by Treisman et al. in 1992. No first order interactions were observed between the periodical phenomenon and the other manipulated factors but only a third order one. Two possible interpretations of these results are proposed.

Adult↗

Resolving inconsistencies in tutor expertise research: does lack of structure cause students to seek tutor guidance?

PURPOSE: To investigate under what conditions tutors' subject-matter expertise influences student achievement. METHOD: Data were analyzed from 1,800 University of Limburg Faculty of Health Sciences students who in 1989-90 participated in tutorial groups led by content-expert staff tutors, non-expert staff tutors, or student tutors. Each student participated in an average of 4.1 tutorial groups. Overall, 4,111 data records were available for analysis. The basic analyses were of (1) students' achievement scores as a function of tutors' levels of subject-matter expertise and students' prior knowledge; (2) students' achievement scores as a function of tutors' levels of subject-matter expertise and educational units' levels of structure; and (3) differences in achievement between students guided by tutors of different levels of expertise in either high- or low-structure units. Statistical methods included analyses of variance. RESULTS: The level of subject-matter expertise of tutors had a positive influence on student achievement. Similar results were found for the students' prior knowledge and the levels of structure of the units; the more prior knowledge students had, the better were their performances on the end-of-unit test; and the higher the level of structure of the unit, the better the achievement. More important, interactions were found between tutor expertise on the one hand and prior knowledge and unit structure on the other, tutor expertise being mainly important if the unit was poorly structured or students reported lack of prior knowledge. CONCLUSION: The results suggest that students need a minimum level of structure in order to profit from problem-based instruction. This structure can be internally provided through prior knowledge available for understanding the new subjects, or offered by the environment in the form of cues of what is relevant and what should be the focus of the activities. If prior knowledge falls short, or if the environment lacks structure, students will turn to their tutors for help and direction. Under those conditions, students who are guided by a subject-matter expert tutor may benefit more than students guided by a non-expert staff tutor or by a student tutor. These findings may explain the widely divergent results of tutor-expertise research.

Achievement↗

Computer assisted data collection in vestibular disorders.

We have developed an interactive database for vertigo than can be used to assist in the diagnostic procedure and to store the data in a form of a database. The database offers the possibility to split and reunite the collected information in a desired way. The database contains detailed information about patient history, symptoms and findings in neurotological, audiological and imaging tests. The symptoms are classified into three sets of questions: vertigo (including postural instability), hearing loss and tinnitus, and provoking factors. Confounding disorders are screened. The neurotological tests involve saccades, smooth pursuit, posturography and caloric test. In addition, findings in specified antibody testing, clinical neurotological tests. MRI, brain stem audiometry and electrocochleography are included. The input information can be applied in an expert system ONE for vertigo work-up. The database is user-friendly. Besides diagnostic purposes the database is excellent for research purposes, and combined with the expert system it works as a tutorial guide for medical students.

Artificial Intelligence↗

Database for vertigo.

An interactive database has been developed to assist the diagnostic procedure for vertigo and to store the data. The database offers a possibility to split and reunite the collected information when needed. It contains detailed information about a patient's history, symptoms, and findings in otoneurologic, audiologic, and imaging tests. The symptoms are classified into sets of questions on vertigo (including postural instability), hearing loss and tinnitus, and provoking factors. Confounding disorders are screened. The otoneurologic tests involve saccades, smooth pursuit, posturography, and a caloric test. In addition, findings from specific antibody tests, clinical neurotologic tests, magnetic resonance imaging, brain stem audiometry, and electrocochleography are included. The input information can be applied to workups for vertigo in an expert system called ONE. The database assists its user in that the input of information is easy. If not only can be used for diagnostic purposes but is also beneficial for research, and in combination with the expert system, it provides a tutorial guide for medical students.

Anxiety↗

BioNeuralNet: a graph neural network based Multi-Omics network data analysis tool.

SUMMARY: Multi-omics data offer unprecedented insights into complex biological systems, yet their high dimensionality, sparsity, and intricate interactions pose significant analytical challenges. Network-based approaches have advanced multi-omics research by effectively capturing biologically relevant relationships among molecular features (e.g., genes, proteins, metabolites). While these methods are powerful for representing molecular interactions, there remains a need for tools specifically designed to effectively utilize these network representations across diverse downstream analyses. To fulfill this need, we introduce BioNeuralNet, a flexible and modular Python framework tailored for end-to-end network-based multi-omics data analysis. BioNeuralNet leverages Graph Neural Networks (GNNs) to learn biologically meaningful low-dimensional representations from multi-omics networks, converting these complex molecular networks into versatile embeddings. BioNeuralNet supports all major stages of multi-omics network analysis, including several network construction techniques, generation of low-dimensional representations, and a broad range of downstream analytical tasks. Its extensive utilities, including diverse GNN architectures, and compatibility with established Python packages (e.g., scikit-learn, PyTorch, NetworkX), enhance usability and facilitate quick adoption. BioNeuralNet is an open-source, user-friendly, and extensively documented framework designed to support flexible and reproducible multi-omics network analysis in precision medicine. AVAILABILITY AND IMPLEMENTATION: The BioNeuralNet library is available via The Python Package Index (PyPI). Source code, documentation, tutorials, and workflows are hosted at https://bioneuralnet.readthedocs.io. Code archived at https://doi.org/10.5281/zenodo.17503083.

Graph Neural Networks↗

High-throughput protein crystallography and drug discovery.

Single crystal X-ray diffraction is the technique of choice for studying the interactions of small organic molecules with proteins by determining their three-dimensional structures; however the requirement for highly purified protein and lack of process automation have traditionally limited its use in this field. Despite these shortcomings, the use of crystal structures of therapeutically relevant drug targets in pharmaceutical research has increased significantly over the last decade. The application of structure-based drug design has resulted in several marketed drugs and is now an established discipline in most pharmaceutical companies. Furthermore, the recently published full genome sequences of Homo sapiens and a number of micro-organisms have provided a plethora of new potential drug targets that could be utilised in structure-based drug design programs. In order to take maximum advantage of this explosion of information, techniques have been developed to automate and speed up the various procedures required to obtain protein crystals of suitable quality, to collect and process the raw X-ray diffraction data into usable structural information, and to use three-dimensional protein structure as a basis for drug discovery and lead optimisation. This tutorial review covers the various technologies involved in the process pipeline for high-throughput protein crystallography as it is currently being applied to drug discovery. It is aimed at synthetic and computational chemists, as well as structural biologists, in both academia and industry, who are interested in structure-based drug design.

Crystallography, X-Ray↗

Sound field measurement tutorial. Working Group on Sound Field Calibration of the Committee on Audiologic Evaluation American Speech-Language-Hearing Association.

Although there are no standards or guidelines for sound field testing, it is recognized that such testing is an integral part of audiologic evaluation. This paper has reviewed some of the problems in sound field testing, as well as possible solutions to those problems. This review may be summarized as follows: 1. The environment in which sound field testing is conducted is an integral part of the test procedure; thus, the ambient noise and reverberation characteristics of the test room must be known. The test room must have ambient noise levels below the level at which the test signals will occur. 2. The listener must be seated so that the SPL of the test signal is known at that listener's pinna. Thus, care must be taken to exclude anything between the ear of the listener and the loudspeaker, and the height of the loudspeaker must be appropriate for the listener. (Note: If the loudspeakers are raised or lowered, it may be necessary to recalibrate.) The near/far field and direct/reverberant field boundaries should be identified and the listener positioned between those two boundaries. 3. The acoustic properties of the test signal must be defined clearly. An FM signal is best for assessing threshold of hearing. The examiner should measure the SPL and verify the spectral characteristics of the signal. The frequency of calibration measurements should be identical to that used for earphones, generally once every 3 months. Finally, it is important to understand the potential interaction between the test environment, the signal, and the listener when testing in the sound field. If the problems are understood and compensations are made it should be possible to obtain reliable and useful auditory information in the sound field.

Acoustics↗

An interactive, student-centered approach to teaching large-group sessions in veterinary clinical pathology.

INTRODUCTION: The purpose of this study was to describe and evaluate an interactive, student-centered approach to teaching large-group sessions in Veterinary Clinical Pathology. The strategy was designed to operate in the place of expository lectures and to encourage a deep approach to learning though discussion and problem solving. METHODOLOGY: The teaching strategy ran over two hours and required students to answer a series of questions on the topic to be discussed before attending the session. In the first part of the session, limited information and laboratory data related to a series of cases were presented to the students for discussion and analysis. These cases were selected on the basis of their usefulness for discussion in relation to the answers to the previously set questions and to reinforce an approach to the analysis of laboratory data. After a break, students were given a series of multiple-choice questions, related to the topic previously discussed, to answer. Students were given the opportunity to discuss the reasons for their answers. Finally, the students were given information and laboratory data from an unknown case and asked to analyze them, through a mechanism previously practiced in small-group tutorials, in order to reach conclusions and to consider the need for further investigation and implications for case management. A consensus diagnosis and plan for the case was reached after reflective observation and discussion. The teaching strategy was evaluated, utilizing teacher reflection and a student questionnaire, on the basis of its success in encouraging active and simulated experiential learning. CONCLUSION: The evaluation of one session indicated that students strongly valued the strategy in relation to actively engaging them in discussion, providing feedback on how they were learning, and enhancing their understanding of how theoretical knowledge can be applied to actual clinical cases. These pedagogical principles appeared to give students greater confidence in analyzing laboratory data through a mechanism of diagnostic reasoning. More sessions of this kind, tied to specific content or skills areas, will allow better evaluation of the perceived student outcomes, which can then be correlated with actual student outcomes through formal assessment.

Education, Veterinary↗

ESTIMA, a tool for EST management in a multi-project environment.

BACKGROUND: Single-pass, partial sequencing of complementary DNA (cDNA) libraries generates thousands of chromatograms that are processed into high quality expressed sequence tags (ESTs), and then assembled into contigs representative of putative genes. Usually, to be of value, ESTs and contigs must be associated with meaningful annotations, and made available to end-users. RESULTS: A web application, Expressed Sequence Tag Information Management and Annotation (ESTIMA), has been created to meet the EST annotation and data management requirements of multiple high-throughput EST sequencing projects. It is anchored on individual ESTs and organized around different properties of ESTs including chromatograms, base-calling quality scores, structure of assembled transcripts, and multiple sources of comparison to infer functional annotation, Gene Ontology associations, and cDNA library information. ESTIMA consists of a relational database schema and a set of interactive query interfaces. These are integrated with a suite of web-based tools that allow a user to query and retrieve information. Further, query results are interconnected among the various EST properties. ESTIMA has several unique features. Users may run their own EST processing pipeline, search against preferred reference genomes, and use any clustering and assembly algorithm. The ESTIMA database schema is very flexible and accepts output from any EST processing and assembly pipeline. ESTIMA has been used for the management of EST projects of many species, including honeybee (Apis mellifera), cattle (Bos taurus), songbird (Taeniopygia guttata), corn rootworm (Diabrotica vergifera), catfish (Ictalurus punctatus, Ictalurus furcatus), and apple (Malus x domestica). The entire resource may be downloaded and used as is, or readily adapted to fit the unique needs of other cDNA sequencing projects. CONCLUSIONS: The scripts used to create the ESTIMA interface are freely available to academic users in an archived format from http://titan.biotec.uiuc.edu/ESTIMA/. The entity-relationship (E-R) diagrams and the programs used to generate the Oracle database tables are also available. We have also provided detailed installation instructions and a tutorial at the same website. Presently the chromatograms, EST databases and their annotations have been made available for cattle and honeybee brain EST projects. Non-academic users need to contact the W.M. Keck Center for Functional and Comparative Genomics, University of Illinois at Urbana-Champaign, Urbana, IL, for licensing information.

Animals↗

PageMan: an interactive ontology tool to generate, display, and annotate overview graphs for profiling experiments.

BACKGROUND: Microarray technology has become a widely accepted and standardized tool in biology. The first microarray data analysis programs were developed to support pair-wise comparison. However, as microarray experiments have become more routine, large scale experiments have become more common, which investigate multiple time points or sets of mutants or transgenics. To extract biological information from such high-throughput expression data, it is necessary to develop efficient analytical platforms, which combine manually curated gene ontologies with efficient visualization and navigation tools. Currently, most tools focus on a few limited biological aspects, rather than offering a holistic, integrated analysis. RESULTS: Here we introduce PageMan, a multiplatform, user-friendly, and stand-alone software tool that annotates, investigates, and condenses high-throughput microarray data in the context of functional ontologies. It includes a GUI tool to transform different ontologies into a suitable format, enabling the user to compare and choose between different ontologies. It is equipped with several statistical modules for data analysis, including over-representation analysis and Wilcoxon statistical testing. Results are exported in a graphical format for direct use, or for further editing in graphics programs.PageMan provides a fast overview of single treatments, allows genome-level responses to be compared across several microarray experiments covering, for example, stress responses at multiple time points. This aids in searching for trait-specific changes in pathways using mutants or transgenics, analyzing development time-courses, and comparison between species. In a case study, we analyze the results of publicly available microarrays of multiple cold stress experiments using PageMan, and compare the results to a previously published meta-analysis.PageMan offers a complete user's guide, a web-based over-representation analysis as well as a tutorial, and is freely available at http://mapman.mpimp-golm.mpg.de/pageman/. CONCLUSION: PageMan allows multiple microarray experiments to be efficiently condensed into a single page graphical display. The flexible interface allows data to be quickly and easily visualized, facilitating comparisons within experiments and to published experiments, thus enabling researchers to gain a rapid overview of the biological responses in the experiments.

Database Management Systems↗

The challenge of "teaching" large groups of learners: strategies to increase active participation and learning.

While teaching in a tutorial, seminar, or problem-based learning group format may be the most fun and most active/interactive for both learner and faculty mentor, there are situations in medical student education in which various constraints require the use of the "lecture" format. Similar constraints may occur in the field of continuing medical education, or graduate medical education, as well. When this occurs, the faculty mentor can increase the active participation of the learners in the audience by continuously stressing seven key pedagogical (androgogical) principles. These include: 1) begin the learning exercise with a clinical example or anecdote to show the relevance of the material to the student; 2) frequently ask the students whether they have ever seen examples of what you describe in their previous experience with patients, personal experience, experience with relatives, etc.; 3) ask students frequently whether they have heard similar material presented differently in other courses; 4) recruit students to help solve "mystery cases"; 5) show examples of similar material from real life (e.g., patient descriptions, or even excerpts from favorite TV shows); 6) ask students to help summarize key points at the end of the session; and 7) allow, or even encourage, whispering during the class. Using some or all of these techniques can help turn a "lecture format" into a much more fun, interactive, and valuable session that emphasizes "learning" rather than "teaching."

Education, Medical↗

Synchrotron radiation circular dichroism spectroscopy of proteins and applications in structural and functional genomics.

The technique of Synchrotron Radiation Circular Dichroism (SRCD) spectroscopy and its advantages over conventional circular dichroism spectroscopy are described in this tutorial review, as well as recent applications of the technique in structural and functional genomics. Circular dichroism (CD) spectroscopy is a well-established method in biological chemistry and structural biology, but its utility can be limited by the low flux of the light source in the far ultraviolet and vacuum ultraviolet wavelength regions in conventional CD instruments. The development of synchrotron radiation circular dichroism (SRCD), using the intense light of a synchrotron beam, has greatly expanded the utility of the method, especially as a tool for both structural and functional genomics. These applications take advantage of the enhanced features of SRCD relative to conventional CD: the ability to measure lower wavelength data containing more electronic transitions and hence more structural information, the higher signal-to-noise hence requiring smaller samples, the higher intensity enabling measurements in absorbing buffers and in the presence of lipids and detergents, and the ability to do faster measurements enabling high throughput and time-resolved spectroscopy.This article discusses recent developments in SRCD instrumentation, software, sample preparation and methods of analyses, with particular emphasis on their applications to the study of proteins. These advances have led to new applications in structural genomics (SG), including the potential for fold recognition as a means of target selection and the examination of membrane proteins, a class of proteins usually excluded from SG programmes. Other SG uses include detection of macromolecular interactions as a screen for complex formation, and examination of glycoproteins and sugar components. In functional genomics (FG) new applications include screening for ligand binding as a means of identifying function, and examination of structural differences in mutant proteins as a means of gaining insight into function.

Circular Dichroism↗

Construction and evaluation of a web-based interactive prescribing curriculum for senior medical students.

AIMS: To develop and evaluate for the National Prescribing Service (NPS) a web-based interactive prescribing curriculum for Australian senior medical students based on the World Health Organization's Guide to Good Prescribing. METHODS: Teachers of prescribing from all Australian medical schools in 2000 wrote 12 case-based modules which were converted to on-line format. Objective evidence was provided for selecting first-line medicines from available alternatives by comparing efficacy, safety, convenience and cost. The curriculum was made available to final year students in 2001 and was evaluated by measuring use from web statistics and by semistructured interviews with 15 teachers (2003) and on-line surveys of 363 students over 2003 and 2004. RESULTS: By 2004 the curriculum was used by nine of 11 possible medical schools. Uptake increased each year from 2001 and all 12 modules were accessed consistently. Student access was significantly (P < 0.001) greater when prescribing was an assessable part of their course. Teachers' evaluations were uniformly supportive and the curriculum is seen as a valuable resource. Student responses came from a small proportion of those with password access but were also supportive. Over half of student respondents had created their own evidence-based formulary. CONCLUSIONS: A collaborative venture initiated by the NPS with Australian medical schools has been successfully implemented in most courses. Teachers find the resource of high quality. Student respondents find the curriculum valuable in developing their own prescribing skills. It is best delivered by self-directed study followed by tutorial discussion of prescribing decisions.

Australia↗

Ion activation methods for tandem mass spectrometry.

This tutorial presents the most common ion activation techniques employed in tandem mass spectrometry. In-source fragmentation and metastable ion decompositions, as well as the general theory of unimolecular dissociations of ions, are initially discussed. This is followed by tandem mass spectrometry, which implies that the activation of ions is distinct from the ionization step, and that the precursor and product ions are both characterized independently by their mass/charge ratios. In collision-induced dissociation (CID), activation of the selected ions occurs by collision(s) with neutral gas molecules in a collision cell. This experiment can be done at high (keV) collision energies, using tandem sector and time-of-flight instruments, or at low (eV range) energies, in tandem quadrupole and ion trapping instruments. It can be performed using either single or multiple collisions with a selected gas and each of these factors influences the distribution of internal energy that the activated ion will possess. While CID remains the most common ion activation technique employed in analytical laboratories today, several new methods have become increasingly useful for specific applications. More recent techniques are examined and their differences, advantages and disadvantages are described in comparison with CID. Collisional activation upon impact of precursor ions on solid surfaces, surface-induced dissociation (SID), is gaining importance as an alternative to gas targets and has been implemented in several different types of mass spectrometers. Furthermore, unique fragmentation mechanisms of multiply-charged species can be studied by electron-capture dissociation (ECD). The ECD technique has been recognized as an efficient means to study non-covalent interactions and to gain sequence information in proteomics applications. Trapping instruments, such as quadrupole ion traps and Fourier transform ion cyclotron resonance instruments, are particularly useful for the photoactivation of ions, specifically for fragmentation of precursor ions by infrared multiphoton dissociation (IRMPD). IRMPD is a non-selective activation method and usually yields rich fragmentation spectra. Lastly, blackbody infrared radiative dissociation is presented with a focus on determining activation energies and other important parameters for the characterization of fragmentation pathways. The individual methods are presented so as to facilitate the understanding of each mechanism of activation and their particular advantages and representative applications.

Chemistry, Clinical↗

Balancing learner control and realism with specific instructional goals: case studies in fluid balance for nursing students.

In designing instruction, there is an inherent tension between permitting learner control and focusing on specific instructional goals. This tension is particularly problematic in computer-based clinical case studies. In addition, the question of the appropriate level of realistic detail is central to case study design. More learner control and greater detail require greater complexity and interactivity, and consequently longer development time per case. They may also lead to difficulty in focusing on specific content. This program is designed to present computer-based case studies as an adjunct to classroom instruction in a specific content area, with significant compromises in realism compensated by the potential to focus on a specific set of problems and expose students to a fairly large number of "patients." The degree of learner control is necessarily limited by the program's structure, but the design attempts to allow a considerable amount of self-direction within those limits. The program's main path goes through a series of case studies illustrating a variety of fluid and electrolyte problems. These case studies are fairly simple and tightly structured: history, physical assessment, and laboratory data are presented near the beginning of each study, and learners are given predefined choices with immediate feedback at specified decision points. The case studies are designed to be completed fairly rapidly, typically no more than about thirty minutes per case. The distortion of the case study format by the obvious focus on fluid and electrolyte problems is compensated somewhat by inclusion of a number of cases with no relevant problems. Within this structured format, the program gives the learner control over a number of aspects of the learning experience. Hypertext is used hierarchically, with two levels of explanation for some central concepts and one level for material not directly relevant to the main instructional goals. Consequently, the learner controls content density to a considerable degree. Since nursing students are under pressure to absorb large amounts of clinically relevant information within a relatively short time, the availability of additional information on diagnoses, charting abbreviations, normal ranges for lab values, etc., may provide an added incentive to use the program. Though the case studies are linear with no branching, learners have several options in using them. The basic user mode involves simply going through the case studies and "solving" them: evaluating the data, identifying problems, and making basic treatment decisions. Alternatively, the learner may choose a particular problem and use the program as a "semi-tutorial." Backward movement is allowed, either to review the development of a case or to try again after an incorrect response. Accumulated information is available in an on-screen "chart" for ready reference. A "reference library" is accessible for browsing from any point in the program. Learner evaluation of the program is in progress.

Computer Simulation↗