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PubMed1990

A computational theory of the hippocampal cognitive map.

Evidence from single unit and lesion studies suggests that the hippocampal formation acts as a spatial or cognitive map (O'Keefe and Nadel, 1978). In this chapter, I summarise some of the unit recording data and then outline the most recent computational version of the cognitive map theory. The novel aspects of the present version of the theory are that it identifies two allocentric parameters, the centroid and the eccentricity, which can be calculated from the array of cues in an environment and which can serve as the bases for an allocentric polar co-ordinate system. Computations within this framework enable the animal to identify its location within an environment, to predict the location which will be reached as a result of any specific movement from that location, and conversely, to calculate the spatial transformation necessary to go from the current location to a desired location. Aspects of the model are identified with the information provided by cells in the hippocampus and dorsal presubiculum. The hippocampal place cells are involved in the calculation of the centroid and the presubicular direction cells in the calculation of the eccentricity.

Animals↗
PubMed2001

Pseudo beam's-eye-view as applied to beam orientation selection in intensity-modulated radiation therapy.

PURPOSE: To introduce the concept of pseudo beam's-eye-view (pBEV), to establish a framework for computer-assisted beam orientation selection in intensity-modulated radiation therapy (IMRT), and to evaluate the utility of the proposed technique. METHODS AND MATERIALS: To facilitate the selection of beam orientations for IMRT treatment planning, a scoring of beam direction was introduced. The score function was based on the maximum target dose deliverable by the beam without exceeding the tolerance doses of the critical structures. For the score function calculation, the beam portal at given gantry and couch angles was divided into a grid of beamlets. Each beamlet crossing the target was assigned the maximum intensity that could be used without exceeding the dose tolerances of the organs at risk (OARs) and normal tissue. Thereafter, a score was assigned to the beam according to the target dose delivered. The beams for the treatment were selected among those with the highest scores. In a sense, this technique is similar to the beam's-eye-view approach used in conventional radiation therapy, except that the evaluation by a human is replaced by a score function, and beam modulation is taken into account. RESULTS: The pBEV technique was tested on two clinical cases: a paraspinal treatment and a nasopharyngeal cancer with both coplanar and noncoplanar beam configurations. The plans generated under the guidance of pBEV for the paraspinal treatment offered superior target dose uniformity and reduced OAR doses. For the nasopharyngeal cancer case, it was also found that the pBEV-selected coplanar and noncoplanar beams significantly improved the target coverage without compromising the sparing of the OARs. CONCLUSIONS: The pBEV technique developed in this work provides a comprehensive tool for beam orientation selection in IMRT. It is especially valuable for complicated cases, where the target is surrounded by several sensitive structures and where it is difficult to select a set of good beam orientations. The pBEV technique has considerable potential for simplifying the IMRT treatment planning process and for maximizing the technical capacity of IMRT.

Humans↗
PubMed2002

A full interionic potential for Na(1+x)Zr(2)Si(x)P(3-x)O(12) superionic conductors.

Most inorganic solids are made up of octahedral and tetrahedral units interconnected to give an infinite framework. Use of computer simulation to study these materials has not been as prevalent as in the organic or biomolecules. Na(1+x)Zr(2)Si(x)P(3-x)O(12) is a typical inorganic solid with ZrO(6) octahedra and (Si/P)O(4) tetrahedra which are shown along with a few Na(+) sites marked M1, M2, and M3. We report here a full interionic potential which reproduces the structure and conductivity of these solids. This augurs well for the study of other inorganic solids.

Journal Article↗
PubMed2001

Conjunctive representations in learning and memory: principles of cortical and hippocampal function.

The authors present a theoretical framework for understanding the roles of the hippocampus and neocortex in learning and memory. This framework incorporates a theme found in many theories of hippocampal function: that the hippocampus is responsible for developing conjunctive representations binding together stimulus elements into a unitary representation that can later be recalled from partial input cues. This idea is contradicted by the fact that hippocampally lesioned rats can learn nonlinear discrimination problems that require conjunctive representations. The authors' framework accommodates this finding by establishing a principled division of labor, where the cortex is responsible for slow learning that integrates over multiple experiences to extract generalities whereas the hippocampus performs rapid learning of the arbitrary contents of individual experiences. This framework suggests that tasks involving rapid, incidental conjunctive learning are better tests of hippocampal function. The authors implement this framework in a computational neural network model and show that it can account for a wide range of data in animal learning.

Animals↗
PubMed2002

Molecular systematics of the Eastern Fence Lizard (Sceloporus undulatus): a comparison of Parsimony, Likelihood, and Bayesian approaches.

Phylogenetic analysis of large datasets using complex nucleotide substitution models under a maximum likelihood framework can be computationally infeasible, especially when attempting to infer confidence values by way of nonparametric bootstrapping. Recent developments in phylogenetics suggest the computational burden can be reduced by using Bayesian methods of phylogenetic inference. However, few empirical phylogenetic studies exist that explore the efficiency of Bayesian analysis of large datasets. To this end, we conducted an extensive phylogenetic analysis of the wide-ranging and geographically variable Eastern Fence Lizard (Sceloporus undulatus). Maximum parsimony, maximum likelihood, and Bayesian phylogenetic analyses were performed on a combined mitochondrial DNA dataset (12S and 16S rRNA, ND1 protein-coding gene, and associated tRNA; 3,688 bp total) for 56 populations of S. undulatus (78 total terminals including other S. undulatus group species and outgroups). Maximum parsimony analysis resulted in numerous equally parsimonious trees (82,646 from equally weighted parsimony and 335 from weighted parsimony). The majority rule consensus tree derived from the Bayesian analysis was topologically identical to the single best phylogeny inferred from the maximum likelihood analysis, but required approximately 80% less computational time. The mtDNA data provide strong support for the monophyly of the S. undulatus group and the paraphyly of "S. undulatus" with respect to S. belli, S. cautus, and S. woodi. Parallel evolution of ecomorphs within "S. undulatus" has masked the actual number of species within this group. This evidence, along with convincing patterns of phylogeographic differentiation suggests "S. undulatus" represents at least four lineages that should be recognized as evolutionary species.

Animals↗
PubMed2003

A divide-and-conquer approach to fragment assembly.

MOTIVATION: One of the major problems in DNA sequencing is assembling the fragments obtained by shotgun sequencing. Most existing fragment assembly techniques follow the overlap-layout-consensus approach. This framework requires extensive computation in each phase and becomes inefficient with increasing number of fragments. RESULTS: We propose a new algorithm which solves the overlap, layout, and consensus phases simultaneously. The fragments are clustered with respect to their Average Mutual Information (AMI) profiles using the k-means algorithm. This removes the unnecessary burden of considering the collection of fragments as a whole. Instead, the orientation and overlap detection are solved efficiently, within the clusters. The algorithm has successfully reconstructed both artificial and real data. AVAILABILITY: Available on request from the authors.

Algorithms↗
PubMed2026

Scaling linear-model breeding values to the liability scale: an application to pig binary traits.

In commercial pig production, many important traits are recorded as binary phenotypes. For such traits, threshold models offer an appropriate framework but are computationally intensive. Thus, linear models are widely used to obtain genomic estimated breeding values (GEBV); however, these are on the observed scale (phenotypic). This creates the need for a robust method to approximate GEBV from linear models to the liability scale. A recently proposed approximation showed good concordance for low-prevalence traits (<5%) but has not yet been tested for a wider range of prevalence values and for models with more than one random effect. We aimed to evaluate the performance of this approximation for pig binary traits with prevalences ranging from <5% to >86%, in both animal and maternal animal models. Data were available for five fitness traits (FT1-FT5), with up to 233k animals with phenotypes, of which 204k animals were genotyped with a 25k SNP array. Variance component estimates were obtained using threshold models. Classical animal models were used for FT1-FT3, and maternal animal models for FT4 and FT5. Variance components on the observed scale were then obtained by multiplying estimates from a threshold model by the square of the height of the standard normal density evaluated at the threshold. GEBV were predicted using single-step genomic best linear unbiased prediction under both linear and threshold models. The approximation tested involved scaling the GEBV using the height of the ordinate of the standard normal distribution evaluated at the threshold as a scaling factor. The agreement between GEBV from the scaled linear model and the threshold model on the probability scale was evaluated using Pearson and Spearman correlations, mean squared error (MSE), regression parameters, overlapping coefficient (OVL), distribution overlap, and classification accuracy (CACC). Correlations between linear and threshold GEBV ranged from 0.94 (low-prevalence traits) to 0.99 (high-prevalence traits) for the direct GEBV and were 0.99 for the maternal GEBV. MSE were close to zero. The OVL exceeded 0.83 for all traits. CACC ranged from 95.10% to 98.33% for the direct GEBV and from 92.54% to 97.42% for the maternal GEBV. Regardless of model and trait prevalence, this approximation yielded GEBV that are highly consistent with threshold model GEBV, providing a reliable, practical approach for large-scale pig genetic evaluations for binary traits using linear models.

Animals↗
PubMed2001

The role of activity-dependent network depression in the expression and self-regulation of spontaneous activity in the developing spinal cord.

Spontaneous episodic activity occurs throughout the developing nervous system because immature circuits are hyperexcitable. It is not fully understood how the temporal pattern of this activity is regulated. Here, we study the role of activity-dependent depression of network excitability in the generation and regulation of spontaneous activity in the embryonic chick spinal cord. We demonstrate that the duration of an episode of activity depends on the network excitability at the beginning of the episode. We found a positive correlation between episode duration and the preceding inter-episode interval, but not with the following interval, suggesting that episode onset is stochastic whereas episode termination occurs deterministically, when network excitability falls to a fixed level. This is true over a wide range of developmental stages and under blockade of glutamatergic or GABAergic/glycinergic synapses. We also demonstrate that during glutamatergic blockade the remaining part of the network becomes more excitable, compensating for the loss of glutamatergic synapses and allowing spontaneous activity to recover. This compensatory increase in the excitability of the remaining network reflects the progressive increase in synaptic efficacy that occurs in the absence of activity. Therefore, the mechanism responsible for the episodic nature of the activity automatically renders this activity robust to network disruptions. The results are presented using the framework of our computational model of spontaneous activity in the developing cord. Specifically, we show how they follow logically from a bistable network with a slow activity-dependent depression switching periodically between the active and inactive states.

Animals↗
PubMed1988

Cohort parity analysis: statistical estimates of the extent of fertility control.

Cohort parity analysis (CPA) is a method for indirect measurement of the extent and timing of the adoption of fertility control within marriage. It uses information on the parity distribution of a cohort of women of specified marriage ages and durations. A multinomial model of parity provides a convenient framework for the computation of distributional parameters describing the extent to which marital fertility control has been accepted and characterizing the way control has been used within specific durations of marriage. This leads to a pair of easily implemented formulas for upper- and lower-bound estimates of the expected proportion of the population ever controlling and the distribution of controllers by parity. The power of CPA is illustrated, using census data for currently married couples in Dublin, Belfast, and other county boroughs of Ireland in 1911.

Adult↗
PubMed1984

CT of the nasopharyngeal region. Normal and pathologic anatomy.

The soft tissue anatomy of the nasopharynx is presented in terms of deglutitional and masticatory muscle layers. Within this framework of analysis, computed tomography can detect relatively early soft tissue changes of nasopharyngeal carcinoma.

Deglutition↗
PubMed1994

Digital archives and communication highways in health care require a second look at the legal framework of the seventies.

The present state of the art and the state of practice regarding legal aspects of medical informatics are reported. Examples are taken from networking, archiving, and virtual reality. It is derived that the data protection concepts of the seventies are covering only some legal aspects of the application scene today and in the future. Thus a far wider legal approach is necessary. It can only be mastered if engineers and lawyers discuss future trends and derive together a new legal framework for medical computer systems in the late nineties. As computers will be everywhere from childhood to death the key issue is not to just protect an individual but to positively frame an information society.

Computer Communication Networks↗
PubMed1993

The receptor revolution--multiplicity of G-protein-coupled receptors.

The superfamily of G-protein-coupled receptors (GPCR) is probably the largest protein-encoding gene family in our genome. It is already known to include hundreds of members and many more are expected to emerge as the molecular cloning revolution proceeds. By definition the GPCR respond to ligands by interacting with intracellular G-proteins and thereby transduce external signals to the interior of the cell. A large body of evidence suggests that the GPCR are organized in the cell membrane like bacteriorhodopsin (BR). All GPCR possess seven hydrophobic membrane-spanning segments which seem to form a characteristic BR-like barrel structure. Thus, the three-dimensional structure of BR may be used as a framework for computer-aided structural modelling of GPCR. The ligands which activate the various members of the GPCR family include an enormous variety of molecules such as amines, amino acids and peptides as well as several small hydrophobic molecules. Many ligands bind to multiple distinct GPCR, e.g. neuropeptide Y (NPY). We have isolated molecular clones encoding a human NPY receptor whose binding properties conform to those of the Y1 subtype. This clone will be a useful tool in our efforts to unravel the molecular mechanisms of the many physiological functions of neuropeptide Y.

Amino Acid Sequence↗
PubMed2025

Automating candidate gene prioritization with large language models: from naive scoring to literature-grounded validation.

MOTIVATION: Identifying promising therapeutic targets from thousands of genes in transcriptomic studies remains a major bottleneck in biomedical research. While large language models (LLMs) show potential for gene prioritization, they suffer from hallucination and lack systematic validation against expert knowledge. RESULTS: The framework identified 609 sepsis-relevant genes with >94% filtering efficiency, demonstrating strong enrichment for inflammatory pathways including TNF-&#x3b1; signaling, complement activation, and interferon responses. Literature validation yielded 30 ultra-high confidence therapeutic candidates, including both established sepsis genes (IL10, TREM1, S100A9, NLRP3) and novel targets warranting investigation. Benchmark validation against expert-curated databases achieved 71.2% recall, with systematic correlation between computational confidence and evidence quality. The final candidate set balanced discovery (11 novel genes) with validation (19 known genes), maintaining biological coherence throughout the filtering process. This framework demonstrates that rigorous methodology can transform unreliable LLM outputs into systematically validated biological insights. By combining computational efficiency with literature grounding, the approach provides a practical tool for prioritizing experimental validation efforts. The modular design enables adaptation to other diseases through knowledge base substitution, offering a systematic approach to literature-guided biomarker discovery. AVAILABILITY AND IMPLEMENTATION: We developed a two-stage computational framework that combines LLM-based screening with literature validation for systematic gene prioritization. Starting with 10&#xa0;824 genes from the BloodGen3 repertoire, we applied multi-criteria evaluation for sepsis relevance, followed by retrieval-augmented generation using 6346 curated sepsis publications. A novel faithfulness evaluation system verified that LLM predictions aligned with retrieved literature evidence. Source code and implementation details are available at https://github.com/taushifkhan/llm-geneprioritization-framework, vector database at https://doi.org/10.5281/zenodo.15802241, and Interactive demonstration at https://llm-geneprioritization.streamlit.app/.

Humans↗
PubMed2001

A formal framework for modelling and validating medical systems.

Medical computerised systems which have a major effect on human lives (e.g. those used for diagnosis, therapy, surgery, in the intensive care units, etc) are considered as safety critical systems. Such systems are sometimes responsible for major damages and injuries due to unpredicted malfunction. Misleading user requirements, errors in the specification and in the implementation are the usual reasons responsible for non-safe systems. This paper advocates the use of an integrated formal framework based on a computational machine (X-Machine), in the development of safety critical medical systems. This formal framework gives the ability to intuitively as well as formally model a system, then automatically check if the produced model has all the desired properties, and finally test if the implementation is equivalent to the specification by applying a complete set of test cases. Therefore, the use of this framework in the development of systems in safety critical medical domains can assure that the final product is valid with respect to the user requirements by revealing errors during the whole development life cycle and subsequently add to the confidence of their use. The proposed framework is accompanied by an example, which demonstrates the use of X-Machines in specification, testing and verification.

Medical Informatics↗
PubMed1994

A framework for "Need to Know" authorizations in medical computer systems: responding to the constitutional requirements.

"Need to Know" systems which restrict access to computerized data to those with a specified need for the data have been described as part of the solution to the problem of privacy in health care information systems. However, no operational "need to know" system is described in the medical literature. Recent legal developments in constitutional privacy protection make a "need to know" system mandatory, not optional. In sophisticated information systems users can utilize the unique characteristics of the system itself to implement a high level "need to know" system, based on the institution's own patient treatment pattern. This article provides an analytical tool for helping to define a "need to know" system with reference to the specific problems of health care institutions.

Civil Rights↗
PubMed2002

Clinical experience of CNC-milled titanium frameworks supported by implants in the edentulous jaw: a 3-year interim report.

BACKGROUND: The use of computer numeric controlled (CNC)-milled titanium frameworks is a new technique for framework fabrication, and few clinical reports have been made on this treatment modality. PURPOSE: The goal of this study was to report the clinical performance of implant-supported prostheses with CNC-milled titanium frameworks in the edentulous jaw and to compare the results with prostheses provided with conventional cast frameworks during the first 3 years of function. MATERIALS AND METHODS: A consecutive group of 126 edentulous patients were provided by random distribution with 67 prostheses with CNC-milled titanium frameworks in 23 upper and 44 lower jaws and 62 conventional prostheses with gold-alloy castings in 31 upper and 31 lower jaws. Radiographic 1-year data and clinical 3-year data were collected for both the titanium and control group. RESULTS: One prosthesis was lost in each group owing to loss of implants, and the overall 3-year prosthesis cumulative survival rate was 98.2% for both groups. Patients with smoking habits experienced significantly more implant failures than nonsmokers (p =.006). Few problems were observed. No metal fractures were seen in the test group, whereas two frameworks and one abutment screw fractured in the control group. Resin veneer fractures were the most common complication, with a slightly higher incidence observed in the control group. CONCLUSIONS: Computer numeric controlled-milled titanium frameworks can be used as an alternative to conventional castings in the edentulous jaw, presenting clinical performance similar to that of conventional cast frameworks during the first 3 years of function. key words: computer numeric controlled, implant supported, prostheses, titanium

Computer-Aided Design↗
PubMed2026

Recent Advances in Multi-Omics of Systemic Lupus Erythematosus.

This comprehensive narrative review examines recent advances in multi-omics research for Systemic Lupus Erythematosus (SLE), emphasizing integrated approaches over single-omics studies. The review critically evaluates technological advancements, methodological innovations, and clinical applications while identifying current limitations and future research directions. We conducted a comprehensive narrative review following SANRA guidelines, searching PubMed, Web of Science, Scopus, and Embase, covering publications from January 2018 to June 2025. The review focuses on studies integrating two or more omics layers in SLE research, with emphasis on computational methods, biomarker validation, and clinical applications. Multi-omics integration has revealed critical insights into SLE pathogenesis, including immune cell heterogeneity, gene-environment interactions, and metabolic dysregulation. However, significant challenges remain in data integration methodologies, small sample sizes, and biomarker reproducibility. Current computational approaches include early integration (concatenation), intermediate integration (joint dimensionality reduction), and late integration (ensemble methods). While multi-omics approaches offer unprecedented insights into SLE complexity, standardized integration protocols and robust validation frameworks are urgently needed. Small sample sizes and heterogeneity issues limit reproducibility, particularly affecting biomarker discovery and clinical translation. Multi-omics integration represents a paradigm shift toward precision medicine in SLE, but realizing this potential requires addressing current methodological limitations, standardizing validation processes, and developing robust computational frameworks for reliable clinical applications.

Humans↗