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At least 289 records · Page 16Linked to original sources
PubMed2026

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 = 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↗
PubMed2003

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↗
PubMed1996

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↗
PubMed1986

A theoretical study of the binding of phenothiazine derivatives to residues 82-93 of calmodulin.

A theoretical study was performed of the interaction of four phenothiazine derivatives, promethazine, promazine, trifluopromazine, and trifluoperazine, with a fragment (82-93) of calmodulin, held in the alpha-helical conformation. The computations were performed in the framework of the SIBFA 2 procedure (sum of interactions between fragments computed ab initio), which uses analytical formulas based on ab initio self-consistent field computations. The interaction energy is the sum of the intermolecular phenothiazine-oligopeptide interaction energy and of the separate intramolecular energy variations of the phenothiazine and of the side chains of the oligopeptide upon complex formation. The ordering of interaction energies of the four investigated phenothiazines parallels the ordering of their experimentally measured affinities for calmodulin, with a maximum affinity for trifluoperazine. The principal features of the trifluoperazine complex are a short hydrogen bond between the piperazinium proton and one anionic oxygen of Glu 87, and hydrophobic interactions between the piperazinium ring and Val 91 and between the methylene chain and Ala 88, together with partial insertion of the phenothiazine ring and the--CF3 substituent between Phe 89 and Phe 92.

Calmodulin↗
PubMed1997

Visual space distortion.

We are surrounded by surfaces that we perceive by visual means. Understanding the basic principles behind this perceptual process is a central theme in visual psychology, psychophysics, and computational vision. In many of the computational models employed in the past, it has been assumed that a metric representation of physical space can be derived by visual means. Psychophysical experiments, as well as computational considerations, can convince us that the perception of space and shape has a much more complicated nature, and that only a distored version of actual, physical space can be computed. This paper develops a computational geometric model that explains why such distortion might take place. The basic idea is that, both in stereo and motion, we perceive the world from multiple views. Given the rigid transformation between the views and the properties of the image correspondence, the depth of the scene can be obtained. Even a slight error in the rigid transformation parameters causes distortion of the computed depth of the scene. The unified framework introduced here describes this distortion in computational terms. We characterize the space of distortions by its level sets, that is, we characterize the systematic distortion via a family of iso-distortion surfaces which describes the locus over which depths are distorted by some multiplicative factor. Given that humans' estimation of egomotion or estimation of the extrinsic parameters of the stereo apparatus is likely to be imprecise, the framework is used to explain a number of psychophysical experiments on the perception of depth from motion or stereo.

Cybernetics↗
PubMedDate not supplied

Precision of CNC-milled titanium frameworks for implant treatment in the edentulous jaw.

PURPOSE: The purpose of this report was to describe a new technique to fabricate one-piece, implant-supported titanium frameworks by means of a computer numeric-controlled (CNC) milling technique, and to compare the fit of these frameworks with conventional cast prostheses. MATERIALS AND METHODS: The study comprised 20 patients who were provided with 5 standard Brånemark implants each in the edentulous mandible. The fit of the first 10 prostheses with CNC-milled frameworks was measured by means of a 3-dimensional photogrammetric technique. The distortion of the center point of the framework cylinders was measured in relation to the master cast replicas. These measurements were compared with 10 randomly selected routine prostheses with cast frameworks. RESULTS: No significant differences were found between the 2 groups. The 3-dimensional distortion of the cylinders in the completed prostheses ranged from 3 to 80 microns; no passive framework was observed. More distortion was observed in the horizontal plane (x and y axes) as compared to the distortion in the vertical direction (z axis). CONCLUSION: The precision of fit of the first CNC-milled prostheses presented a comparable fit to the conventional cast frameworks. Consequently, this new technique could be a valid option for the routine fabrication of frameworks for implant prostheses.

Computer-Aided Design↗
PubMed2000

Statistical issues in toxicokinetic modeling: a bayesian perspective.

Determining the relationship between an exposure and the resulting target tissue dose is a critical issue encountered in quantitative risk assessment (QRA). Classical or physiologically based toxicokinetic (PBTK) models can be useful in performing that task. Interest in using these models to improve extrapolations between species, routes, and exposure levels in QRA has therefore grown considerably in recent years. In parallel, PBTK models have become increasingly sophisticated. However, development of a strong statistical foundation to support PBTK model calibration and use has received little attention. There is a critical need for methods that address the uncertainties inherent in toxicokinetic data and the variability in the human populations for which risk predictions are made and to take advantage of a priori information on parameters during the calibration process. Natural solutions to these problems can be found in a Bayesian statistical framework with the help of computational techniques such as Markov chain Monte Carlo methods. Within such a framework, we have developed an approach to toxicokinetic modeling that can be applied to heterogeneous human or animal populations. This approach also expands the possibilities for uncertainty analysis. We present a review of these efforts and other developments in these areas. Appropriate statistical treatment of uncertainty and variability within the modeling process will increase confidence in model results and ultimately contribute to an improved scientific basis for the estimation of occupational and environmental health risks.

Bayes Theorem↗
PubMed2003

Can patients with osteoporosis, who should benefit from implementation of the national service framework for older people, be identified from general practice computer records? A pilot study that illustrates the variability of computerized medical records and problems with searching them.

Although UK general practice is highly computerized, comprehensive use of these computers is often limited to registration data and the issue of repeat prescriptions. The recording of diagnostic data is patchy. This study examines whether patients with, or at risk of, osteoporosis can be readily identified from general practice computer records. It reports the findings of a pilot study designed to show the variability of recording the diagnosis of osteoporosis and osteopenia, as well as how useful surrogate markers might be to identify these patients. The study also illustrates the difficulties that even skilled practitioners in a primary care research network experience in extracting clinical data from practice information systems. Computer searches were carried out across six practices in a general practice research network in the south-east of England. Two of these practices had previously undertaken research projects in osteoporosis and were consequently expected to have excellent data quality in osteoporosis. These two practices had a combined list size of 27,500 and the remaining practices had a combined practice population of 43,000 patients. The data were found to be variable with over 10-fold differences between practices in the recorded prevalence of osteoporosis diagnosis as well as its surrogate markers-such as fragility fractures, long-term steroid prescription, etc. There was no difference in data quality between the two practices that had conducted osteoporosis research and the rest of the group, other than in the areas of diagnostic recording and prescribing for osteoporosis and recording of fractures. Issues were raised by the practices that struggled to identify patients at risk of osteoporosis about the limitations of Read classification in this disease area. Practices need further assistance if the patients at risk are to be identified. Without urgent action, it will be difficult for practices to identify the patients who are likely to benefit from Standard 6-'Falls' of the National Service Framework for Older People. These findings also have broader implications as UK general practice moves towards the implementation of a quality-based contract.

Aged↗
PubMed2004

Interaction between charged anisotropic macromolecules: application to rod-like polyelectrolytes.

In this paper we propose a framework allowing one to compute the effective interactions between two anisotropic macromolecules, thereby generalizing the Derjaguin, Landau, Verwey, and Overbeek theory [E. J. W. Verwey and J. T. G. Overbeek, Theory of the Stability of Lyophobic Colloids (Elsevier, Amsterdam, 1948)] to nonspherical finite size colloids. We show in particular that the effective interaction potential remains anisotropic at all distances and provide an expression for the anisotropy factor. We then apply this framework to the case of finite rod-like polyelectrolytes. The calculation of the interaction energy requires the numerical computation of the surface charge profiles, which result here from a constant surface potential on the rod-like colloids. However, a simplified analytical description is proposed, leading to an excellent agreement with the full numerical solution. Conclusions on the phase properties of rod-like colloids are proposed in this context.

Journal Article↗
PubMed2026

Beyond antigen matching: compatibility intelligence theory for transfusion as an emergent biological system.

BACKGROUND: Despite major advances in serologic testing, extended phenotyping, and blood group genomics, clinically similar transfusion exposures may result in markedly different immune and clinical outcomes. Existing compatibility strategies do not fully explain this biological variability. OBJECTIVES: To examine transfusion compatibility as an emergent donor-recipient biological state and propose a systems-level conceptual framework that integrates established biological determinants into a testable model for future precision transfusion medicine. METHODS: This narrative review critically synthesizes current evidence from blood group genomics, recipient immunobiology, inflammation, disease-specific biology, transfusion medicine, and computational prediction. The proposed framework distinguishes Compatibility Intelligence Theory (CIT) as a biological interpretation from Precision Transfusion Intelligence (PTI) as its potential clinician-supervised translational application. RESULTS: The review argues that transfusion compatibility is shaped by interactions among donor genetics, recipient immune biology, inflammatory physiology, disease context, transfusion history, and longitudinal adaptation rather than by antigen matching alone. CIT provides an organizational framework for integrating these determinants, whereas PTI describes a possible clinician-supervised translation. To address current feasibility, the revised framework separates variables into routinely measurable, contextually available but incompletely standardized, and research-stage domains, and proposes a staged strategy for deriving rather than assuming their quantitative weights. Any clinical implementation would require comparative validation against current serologic, phenotypic, and genotype-based practice. CONCLUSIONS: Compatibility Intelligence Theory offers a testable systems-level framework for understanding transfusion compatibility without replacing established transfusion practices. The framework is not presented as a ready-to-use score: currently measurable variables can be organized for structured risk review, whereas inflammatory, immunogenetic, and multi-omic inputs require prospective standardization and validation. If future studies demonstrate incremental predictive and patient-centered benefit, CIT-informed PTI could support an adaptive, evidence-based extension of current precision transfusion practice.

Humans↗
PubMed2003

Human factors: imperative concepts for information systems in critical care.

This article provides an overview of human factors, ergonomics, human-computer interaction, and usability concepts as they relate to critical care settings. The use of these concepts can improve patient safety and the productivity of nurses, especially as they relate to the use of information systems. A framework for human-computer interaction is presented. Examples illustrate how the suite of human factors concepts is used to create intuitive, effective data presentations for use in critical care including an intensive care unit (ICU) summary display, an alternative graphic display, and modeling information sources of decision making in a neonatal ICU. The importance of integrating these concepts into advanced practice nurses' environments is made apparent.

Critical Care↗
PubMed2000

[Testing a computer-assisted bending machine for manufacturing orthodontic treatment elements].

The use of suitable orthodontic devices producing desired defined force systems is of importance for successful orthodontic treatment. Bending loops can be difficult and time-consuming. Computerised fabrication would enable very precise reproduction of individual loops. A bending machine has now been developed within the framework of a computer-assisted treatment concept. In this study, a prototype machine was used to fabricate U-, T- and delta loops made of stainless steel, cobalt chromium and titanium molybdenum wire. The various geometric parameters of each loop were measured to determine how precisely they had been produced. Furthermore, the force system of each loop were experimentally investigated during simulated activation in an orthodontic measurement and simulation system. The results indicate that the geometric parameters had an average error of 2.8 degrees for angles and 0.9 mm for lengths. Owing to the fabrication errors, loops of the same type produced different force systems. Overall, the new bending machine can fabricate different types of loop, but the requirements of very precise fabrication are currently not met. This fact, together with further limitations in terms of configuration, means that the machine cannot be used routinely at present. However, the machine can nevertheless be considered a good basis for further development.

Computer-Aided Design↗
PubMed2003

Inferring genetic networks and identifying compound mode of action via expression profiling.

The complexity of cellular gene, protein, and metabolite networks can hinder attempts to elucidate their structure and function. To address this problem, we used systematic transcriptional perturbations to construct a first-order model of regulatory interactions in a nine-gene subnetwork of the SOS pathway in Escherichia coli. The model correctly identified the major regulatory genes and the transcriptional targets of mitomycin C activity in the subnetwork. This approach, which is experimentally and computationally scalable, provides a framework for elucidating the functional properties of genetic networks and identifying molecular targets of pharmacological compounds.

Algorithms↗
PubMed2004

Exact lattice calculations of dispersion coefficients in the presence of external fields and obstacles.

We present a study of the field-dependent dispersion coefficient of point-like particles in various 2D overdamped systems with obstructions (periodic, percolating, and trapping distributions of obstacles). These calculations profit from the synthesis of a newly proposed Monte Carlo algorithm--the first such algorithm that correctly reproduces the free dispersion coefficient in the presence of finite external fields--and an asymptotically exact calculation technique. The resulting method efficiently produces algebraic and numerical results without the need to actually perform Monte Carlo simulations. When compared to such simulations, our exact method features a negligible computational cost and exponentially small errors. Utilizing the power of this numerical method, we engage in comprehensive parametric analysis of several model systems, revealing very subtle effects that would otherwise be swamped by statistical errors or incur prohibitive computational costs. The unified framework presented here serves as a template for further applications of lattice random-walk models of biased diffusion.

Algorithms↗
PubMed2001

Epidemic spreading in scale-free networks.

The Internet has a very complex connectivity recently modeled by the class of scale-free networks. This feature, which appears to be very efficient for a communications network, favors at the same time the spreading of computer viruses. We analyze real data from computer virus infections and find the average lifetime and persistence of viral strains on the Internet. We define a dynamical model for the spreading of infections on scale-free networks, finding the absence of an epidemic threshold and its associated critical behavior. This new epidemiological framework rationalizes data of computer viruses and could help in the understanding of other spreading phenomena on communication and social networks.

Communication↗
PubMed1985

A theoretical investigation on the sequence selective binding of daunomycin to double-stranded polynucleotides.

Theoretical computations are performed on the structural and energetical factors involved in the sequence selective binding of daunomycin (DNM) to six representative self-complementary double-stranded hexanucleotides: d(CGTACG)2,d(CGATCG)2,d(CITACI)2, d(TATATA)2, d(CGCGCG)2 and d(TACGTA)2. The conformational angles of the hexanucleotides are fixed in values found in the representative crystal structure of the d(CGTACG)2-DNM complex. The intermolecular DNM-hexanucleotide interaction energies and the conformational energy changes of DNM upon binding are computed and optimized in the framework of the SIBFA procedure, which uses empirical formulas based on ab initio SCF computations. Among the two regularly alternating hexanucleotides, d(TATATA)2 and d(CGCGCG)2, a stronger binding is predicted for the former, in agreement with experimental results obtained with poly(dA-dT).poly(dA-dT) and poly(dG-dC).poly(dG-dC). Altogether, however, among the six investigated sequences, the strongest complexes are computed for the mixed hexanucleotides d(CGATCG)2 and d(CGTACG)2, containing the intercalation site between two CG base pairs and an adjacent TA base pair. This situation may be related to the increased affinity of DNM for GC rich DNA's and to the situation in the crystal structure of the DNM-d(CGTACG)2 complex. Analysis of the intrinsic base sequence preferences expressed by the individual constituents of DNM, namely the daunosamine side chain, the chromophore ring and its two 9-hydroxyl and 9-acetoxy substituents, reveals that the overall sequence preference found is the result of a rather intricate interplay of intrinsic sequence preferences, in particular at the level of daunosamine and the 9-hydroxyl substituent.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Structural features of the bradykinin receptor as determined by computer simulations, mutagenesis experiments, and conformationally constrained ligands: establishing the framework for the design of new antagonists.

1. In recent years, two classes of second generation bradykinin receptor antagonists have been reported. Both are of the general sequence D-Arg0-Arg1-Pro2-W3-Gly4-X5-Ser6-Y7-Z8+ ++-Arg9, where W is either Pro or Hyp, and X is an aromatic or aliphatic side chain-containing amino acid. Y and Z are unnatural amino acids, presumed to enforce a beta-turn structure. The de novo design of a non-peptide receptor antagonist (or the optimization of a lead discovered by random screening) will ultimately require knowledge about the receptor topology. In the absence of an experimentally determined structure of the bradykinin-bradykinin receptor complex, we have attempted to gain insights from other sources. 2. We have synthesized conformationally constrained ligands and completed extensive computer modeling on the bradykinin receptor. Moreover, using systematic synthetic modifications, we have explored the relative importances of selected amide bonds and side chains in second generation peptides and have made a series of C alpha- and/or N-methyl substitutions at positions four and five which led to the discovery of two new cyclic peptide antagonists. 3. Computational simulations led to a proposed model of bradykinin bound to its receptor which was found to be in good agreement with mutagenesis results. This model led ultimately to the design and synthesis of D-Arg0-Arg1-(12-aminododecanoyl)2-Ser3-D-Tic4-Oic5+ ++-Arg6. Consideration of this new lead compound, together with the extensive structure-activity relationship (SAR) which has been developed for peptide ligands and the receptor, represents a tangible framework for the design of more potent and longer-lasting antagonists of the bradykinin receptor.

Amino Acid Sequence↗
PubMed2003

Modelling intracellular H(+) ion diffusion.

Intracellular pH, an important modulator of cell function, is regulated by plasmalemmal proteins that transport H(+), or its equivalent, into or out of the cell. The pH(i) is also stabilised by high-capacity, intrinsic buffering on cytoplasmic proteins, oligopeptides and other solutes, and by the extrinsic CO(2)/HCO(3)(-) (carbonic) buffer. As mobility of these buffers is lower than for the H(+) ion, they restrict proton diffusion. In this paper we use computational approaches, based on the finite difference and finite element methods (FDM and FEM, respectively), for analysing the spatio-temporal behaviour of [H(+)] when it is locally perturbed. We analyse experimental data obtained for various cell-types (cardiac myocytes, duodenal enterocytes, molluscan neurons) where pH(i) has been imaged confocally using intracellular pH-sensitive dyes. We design mathematical algorithms to generate solutions for two-dimensional diffusion that fit data in terms of an apparent intracellular H(+) diffusion coefficient, D(H)(app). The models are used to explore how the spatial distribution of [H(+)](i) is affected by membrane H(+)-equivalent transport and by cell geometry. We then develop a mechanistic model, describing spatio-temporal changes of [H(+)](i) in a cardiac ventricular myocyte in terms of H(+)-shuttling on mobile buffers and H(+)-anchoring on fixed buffers. We also discuss how modelling may include the effects of extrinsic carbonic-buffering. Overall, our computational approach provides a framework for future analyses of the physiological consequences of pH(i) non-uniformity.

Animals↗