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A sense of life: computational and experimental investigations with models of biochemical and evolutionary processes.

We collaborate in a research program aimed at creating a rigorous framework, experimental infrastructure, and computational environment for understanding, experimenting with, manipulating, and modifying a diverse set of fundamental biological processes at multiple scales and spatio-temporal modes. The novelty of our research is based on an approach that (i) requires coevolution of experimental science and theoretical techniques and (ii) exploits a certain universality in biology guided by a parsimonious model of evolutionary mechanisms operating at the genomic level and manifesting at the proteomic, transcriptomic, phylogenic, and other higher levels. Our current program in "systems biology" endeavors to marry large-scale biological experiments with the tools to ponder and reason about large, complex, and subtle natural systems. To achieve this ambitious goal, ideas and concepts are combined from many different fields: biological experimentation, applied mathematical modeling, computational reasoning schemes, and large-scale numerical and symbolic simulations. From a biological viewpoint, the basic issues are many: (i) understanding common and shared structural motifs among biological processes; (ii) modeling biological noise due to interactions among a small number of key molecules or loss of synchrony; (iii) explaining the robustness of these systems in spite of such noise; and (iv) cataloging multistatic behavior and adaptation exhibited by many biological processes.

Animals↗

A framework for analyzing the cognitive complexity of computer-assisted clinical ordering.

Computer-assisted provider order entry is a technology that is designed to expedite medical ordering and to reduce the frequency of preventable errors. This paper presents a multifaceted cognitive methodology for the characterization of cognitive demands of a medical information system. Our investigation was informed by the distributed resources (DR) model, a novel approach designed to describe the dimensions of user interfaces that introduce unnecessary cognitive complexity. This method evaluates the relative distribution of external (system) and internal (user) representations embodied in system interaction. We conducted an expert walkthrough evaluation of a commercial order entry system, followed by a simulated clinical ordering task performed by seven clinicians. The DR model was employed to explain variation in user performance and to characterize the relationship of resource distribution and ordering errors. The analysis revealed that the configuration of resources in this ordering application placed unnecessarily heavy cognitive demands on the user, especially on those who lacked a robust conceptual model of the system. The resources model also provided some insight into clinicians' interactive strategies and patterns of associated errors. Implications for user training and interface design based on the principles of human-computer interaction in the medical domain are discussed.

Cognition↗

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↗

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↗

Computational modeling of healing: an application of the material force method.

The basic aim of the present contribution is the qualitative simulation of healing phenomena typically encountered in hard and soft tissue mechanics. The mechanical framework is provided by the theory of open system thermodynamics, which will be formulated in the spatial as well as in the material motion context. While the former typically aims at deriving the density and the spatial motion deformation field in response to given spatial forces, the latter will be applied to determine the material forces in response to a given density and material deformation field. We derive a general computational framework within the finite element context that will serve to evaluate both the spatial and the material motion problem. However, once the spatial motion problem has been solved, the solution of the material motion problem represents a mere post-processing step and is thus extremely cheap from a computational point of view. The underlying algorithm will be elaborated systematically by means of two prototype geometries subjected to three different representative loading scenarios, tension, torsion, and bending. Particular focus will be dedicated to the discussion of the additional information provided by the material force method. Since the discrete material node point forces typically point in the direction of potential material deposition, they can be interpreted as a driving force for the healing mechanism.

Animals↗

A point process framework for relating neural spiking activity to spiking history, neural ensemble, and extrinsic covariate effects.

Multiple factors simultaneously affect the spiking activity of individual neurons. Determining the effects and relative importance of these factors is a challenging problem in neurophysiology. We propose a statistical framework based on the point process likelihood function to relate a neuron's spiking probability to three typical covariates: the neuron's own spiking history, concurrent ensemble activity, and extrinsic covariates such as stimuli or behavior. The framework uses parametric models of the conditional intensity function to define a neuron's spiking probability in terms of the covariates. The discrete time likelihood function for point processes is used to carry out model fitting and model analysis. We show that, by modeling the logarithm of the conditional intensity function as a linear combination of functions of the covariates, the discrete time point process likelihood function is readily analyzed in the generalized linear model (GLM) framework. We illustrate our approach for both GLM and non-GLM likelihood functions using simulated data and multivariate single-unit activity data simultaneously recorded from the motor cortex of a monkey performing a visuomotor pursuit-tracking task. The point process framework provides a flexible, computationally efficient approach for maximum likelihood estimation, goodness-of-fit assessment, residual analysis, model selection, and neural decoding. The framework thus allows for the formulation and analysis of point process models of neural spiking activity that readily capture the simultaneous effects of multiple covariates and enables the assessment of their relative importance.

Action Potentials↗

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↗

A theoretical study of the comparative binding affinities of daunomycin derivatives to a double-stranded oligomeric DNA. Proposal for new high affinity derivatives.

Theoretical computations were performed on the comparative binding affinities of daunomycin (DM, 1) and seven derivatives related to the double-stranded oligonucleotide d(CGATCG)2. The compounds investigated were 4-demethoxy DM (2), and its beta-anomer (3), 4-demethoxy-7,9-bis-epi DM (4) and its beta anomer (5), a derivative with glucosamine instead of daunosamine (6), and two additional hypothetical DM derivatives in which the cationic NH3+ group of the daunosamine moiety is replaced by either a CH2--NH3+ group (7) or a CH2CH2NH3+ group (8), so as to indicate the effect on the binding affinity of interposing one- or two-methylene groups between the sugar and the cationic charge. The conformational angles of the hexanucleotide are fixed in values found in the representative crystal structure of the d(CGTACG)2-DM complex. The intermolecular drug-hexanucleotide interaction energies and the conformational energy changes of the drug upon binding are computed and optimized in the framework of the SIBFA procedure (sum of interactions between fragments computed ab initio), which uses empirical formulas based on ab initio SCF computations. The overall binding affinity ordering of compounds 1-6 compares satisfactorily with the ordering of available experimental affinity constants. The binding affinities of compounds 7 and 8, for which no experimental results seem to be available yet, are predicted to be significantly higher than those of the parent compound DM, with the greatest affinity found for 7. Because of the overall correlation between binding affinity of anthracyclines to DNA and their antitumor activity, these last two compounds deserve an exploration of their chemotherapeutic efficiency.

DNA↗

Computational models of neuromodulation.

Computational modeling of neural substrates provides an excellent theoretical framework for the understanding of the computational roles of neuromodulation. In this review, we illustrate, with a large number of modeling studies, the specific computations performed by neuromodulation in the context of various neural models of invertebrate and vertebrate preparations. We base our characterization of neuromodulations on their computational and functional roles rather than on anatomical or chemical criteria. We review the main framework in which neuromodulation has been studied theoretically (central pattern generation and oscillations, sensory processing, memory and information integration). Finally, we present a detailed mathematical overview of how neuromodulation has been implemented at the single cell and network levels in modeling studies. Overall, neuromodulation is found to increase and control computational complexity.

Animals↗

Management policies and procedures needed for effective computer security.

Although many security issues are controlled by legislative ruling and social standards, or are constrained by technological limitations, many other important matters of operational computer security are directly or indirectly under managerial control. The author argues that the necessary control policies and procedures will become increasingly critical as our reliance upon computer-based information systems continues to increase. This article presents a comprehensive framework for understanding the various aspects of computer security. Through this framework, those areas controllable by management are identified, and possible actions are proposed.

Attitude↗

Parieto-frontal coding of reaching: an integrated framework.

In the last few years, anatomical and physiological studies have provided new insights into the organization of the parieto-frontal network underlying visually guided arm-reaching movements in at least three domains. (1) Network architecture. It has been shown that the different classes of neurons encoding information relevant to reaching are not confined within individual cortical areas, but are common to different areas, which are generally linked by reciprocal association connections. (2) Representation of information. There is evidence suggesting that reach-related populations of neurons do not encode relevant parameters within pure sensory or motor "reference frames", but rather combine them within hybrid dimensions. (3) Visuomotor transformation. It has been proposed that the computation of motor commands for reaching occurs as a simultaneous recruitment of discrete populations of neurons sharing similar properties in different cortical areas, rather than as a serial process from vision to movement, engaging different areas at different times. The goal of this paper was to link experimental (neurophysiological and neuroanatomical) and computational aspects within an integrated framework to illustrate how different neuronal populations in the parieto-frontal network operate a collective and distributed computation for reaching. In this framework, all dynamic (tuning, combinatorial, computational) properties of units are determined by their location relative to three main functional axes of the network, the visual-to-somatic, position-direction, and sensory-motor axis. The visual-to-somatic axis is defined by gradients of activity symmetrical to the central sulcus and distributed over both frontal and parietal cortices. At least four sets of reach-related signals (retinal, gaze, arm position/movement direction, muscle output) are represented along this axis. This architecture defines informational domains where neurons combine different inputs. The position-direction axis is identified by the regular distribution of information over large populations of neurons processing both positional and directional signals (concerning the arm, gaze, visual stimuli, etc.) Therefore, the activity of gaze- and arm-related neurons can represent virtual three-dimensional (3D) pathways for gaze shifts or hand movement. Virtual 3D pathways are thus defined by a combination of directional and positional information. The sensory-motor axis is defined by neurons displaying different temporal relationships with the different reach-related signals, such as target presentation, preparation for intended arm movement, onset of movements, etc. These properties reflect the computation performed by local networks, which are formed by two types of processing units: matching and condition units. Matching units relate different neural representations of virtual 3D pathways for gaze or hand, and can predict motor commands and their sensory consequences. Depending on the units involved, different matching operations can be learned in the network, resulting in the acquisition of different visuo-motor transformations, such as those underlying reaching to foveated targets, reaching to extrafoveal targets, and visual tracking of hand movement trajectory. Condition units link these matching operations to reinforcement contingencies and therefore can shape the collective neural recruitment along the three axes of the network. This will result in a progressive match of retinal, gaze, arm, and muscle signals suitable for moving the hand toward the target.

Animals↗

[Computer-assisted design in removable partial dentures. Expert system and software for framework tracing].

Stelligraph, a software program for designing the removable partial denture offers many possibilities in computer assisted technology. The design can be realized on any particular case, based on three different concepts. This software program can also provide on individual, manual and personalized design this offening complete freedom in the conception. This software program is an expert system in removable partial denture by providing the general practitioner with a rational design as well as clinical guidance for oral rehabilitation.

Denture Design↗

Comparisons of precision of fit between cast and CNC-milled titanium implant frameworks for the edentulous mandible.

PURPOSE: The purpose of this study was to investigate and compare the precision of fabrication in repeatqdly produced computer numeric controlled (CNC)-milled frameworks with consventional castings, and to analyze the distortion from application of different veneering materials. MATERIALS AND METHODS: Twenty identical titanium frameworks were fabricated by means of a CNC milling technique for the same master model. Five conventional frameworks were cast as a control group to the same model. The frames were measured with regard to fit in a coordinate measuring machine linked to a computer. Measurements were made during different stages of handling of the titanium framework, and after veneering materials had been applied. RESULTS: The CNC frameworks showed a statistically better fit and precision of fabrication compared to conventional castings (P < .05). The application of veneering material did not statistically affect the fit of the titanium frameworks (P > .05). CONCLUSION: It is possible to fabricate implant-supported frameworks by means of the present CNC technique with a very high precision and repeatability.

Acrylic Resins↗

Quantum computing-assisted validation of a conserved macrophage suppression module shared by ASFV and PEDV.

BACKGROUND: African swine fever virus (ASFV) and porcine epidemic diarrhea virus (PEDV) differ in viral biology and cellular tropism, yet both pathogens suppress macrophage-mediated immune responses in pigs. OBJECTIVE: To identify a conserved macrophage suppression module shared by ASFV and PEDV and evaluate quantum computing as an independent framework for biological network validation. METHODS: Integrated analysis of publicly available GEO datasets (GSE231435 for ASFV and GSE306895) identified 471 shared downregulated genes. A network- and multi-omics-informed 20-gene core was selected and encoded as a 20-qubit modularity-based Quadratic Unconstrained Binary Optimization (QUBO) problem. Community detection was benchmarked using the Quantum Approximate Optimization Algorithm (QAOA) on both the IBM Quantum Aer simulator and the 156-qubit IBM Fez (Heron r2) quantum processor and compared with brute-force enumeration and simulated annealing. RESULTS: A conserved macrophage suppression module shared by ASFV and PEDV was identified. For the STRING protein-protein interaction network, QAOA at circuit depth p&#x2009;=&#x2009;3 reproduced the brute-force optimum with an approximation ratio of 1.000. In contrast, performance progressively declined in the denser co-expression network with increasing circuit depth, consistent with noise accumulation under current Noisy Intermediate-Scale Quantum (NISQ) conditions. Multi-run consensus analysis identified stable hub genes, including MMP9 and SLA-DOA, as well as genes exhibiting variable community assignments. CONCLUSION: These findings reveal a conserved macrophage suppression module shared between ASFV and PEDV and demonstrate that quantum computing can serve as an independent validation framework for biologically meaningful host-response networks. Network topology emerged as a key determinant of QAOA performance on real NISQ hardware.

Animals↗

Using patient-driven computers to provide cost-effective prevention in primary care: a conceptual framework.

This paper initially presents a rationale for the cost-effectiveness of using patient-driven computers in primary care services. It specifically defines the concepts of prevention and primary care, prior to outlining the advantages of promoting the implementation of prevention practices in primary care. It argues that greater use of computer technology represents one means of cost-effectively optimizing the integration of prevention into routine primary care, and identifies an apparent disjuncture between the potential of computers and the limited success with which attempts to integrate them into routine primary care services have been met, as evidenced in the published international literature. Among several possible explanations for this disjuncture, such as a possible lack of precision with which computers identify at-risk patients, perceived high costs associated with computers and physicians' concerns about the inflexibility and the more impersonal nature of computer interactions, is the apparent failure of researchers to utilize well designed and empirically tested models in the planning, implementation and evaluation of computerized care. An outline for such an approach, utilizing the Precede-Proceed model of health promotion planning and the Diffusion of Innovations theory, is presented.

British Columbia↗

A Bayesian evolutionary distance for parametrically aligned sequences.

There is an inherent relationship between the process of pairwise sequence alignment and the estimation of evolutionary distance. This relationship is explored and made explicit. Assuming an evolutionary model and given a specific pattern of observed base mismatches, the relative probabilities of evolution at each evolutionary distance are computed using a Bayesian framework. The mean or the median of this probability distribution provides a robust estimate of the central value. The evolutionary distance has traditionally been computed as zero for an observed homology of 20 bases with no mismatches; we prove that it is highly probable that the distance is greater than 0.01. The mean of the distribution is 0.047, which is a better estimate of the evolutionary distance. Bayesian estimates of the evolutionary distance incorporate arbitrary prior information about variable mutation rates both over time and along sequence position, thus requiring only a weak form of the molecular-clock hypothesis. The endpoints of the similarity between genomic DNA sequences are often ambiguous. The probability of evolution at each evolutionary distance can be estimated over the entire set of alignments by choosing the best alignment at each distance and the corresponding probability of duplication at that evolutionary distance. A central value of this distribution provides a robust evolutionary distance estimate. We provide an efficient algorithm for computing the parametric alignment, considering evolutionary distance as the only parameter. These techniques and estimates are used to infer the duplication history of the genomic sequence in C. elegans and in S. cerevisiae. Our results indicate that repeats discovered using a single scoring matrix show a considerable bias in subsequent evolutionary distance estimates.

Animals↗

Quantifying motion in video recordings of neonatal seizures by regularized optical flow methods.

This paper presents the development of regularized optical flow computation methods and an evaluation of their performance in the extraction of quantitative motion information from video recordings of neonatal seizures. A general formulation of optical flow computation is presented and a mathematical framework for the development of practical tools for computing optical flow is outlined. In addition, this paper proposes an alternative formulation of the optical flow problem that relies on a discrete approximation of a family of quadratic functionals. These regularized optical flow computation methods are used to extract motion strength signals from video recordings of neonatal seizures.

Algorithms↗