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Theoretical modeling of micro-scale biological phenomena in human coronary arteries.

This paper presents a mathematical model of biological structures in relation to coronary arteries with atherosclerosis. A set of equations has been derived to compute blood flow through these transport vessels with variable axial and radial geometries. Three-dimensional reconstructions of diseased arteries from cadavers have shown that atherosclerotic lesions spiral through the artery. The theoretical framework is able to explain the phenomenon of lesion distribution in a helical pattern by examining the structural parameters that affect the flow resistance and wall shear stress. The study is useful for connecting the relationship between the arterial wall geometries and hemodynamics of blood. It provides a simple, elegant and non-invasive method to predict flow properties for geometrically complex pathology at micro-scale levels and with low computational cost.

Biomechanical Phenomena↗

Dehydrated and Cs+-exchanged MFI zeolites: location and population of Cs+ from in situ diffraction data as a function of temperature and degree of exchange.

H-MFI type zeolitic materials of different Si/Al ratios have been completely or partially cesium-exchanged (cesium content ranging from 0.7 to 7.7 Cs/unit-cell (uc)). Examined with synchrotron X-ray powder diffractometry, an anhydrous sample with the Cs6.6H0.3Al6.9Si89.1O192 chemical composition revealed at ambient temperature the presence of five discrete Cs locations: Cs1 located in the channel intersection near a 10-ring window of the zigzag channel; Cs2 and Cs2', both located in the straight channel but 1.23 A apart; Cs3 and Cs3', both located in the zigzag channel and rather close to each other (2.51 A). The populations of the Cs species amounted to 2.61/0.81/1.85/0.86/0.47/uc for Cs1/2/2'/3/3', respectively. The continuous but multimodal nature of the C2 split site is well-described by a joint-probability density function. The 10-ring of the straight channel in the framework is highly elliptical (epsilon = 1.218). The populations for the same sites were also determined at higher temperatures: 131, 237, 344, and 450 degrees C. At 450 degrees C, Cs2' has migrated toward the center of the channel intersection, and the site separation between Cs2 and Cs2' has lengthened to 2.23 A. Using a temperature-controlled laboratory X-ray diffractometer, similar studies were carried out on partially or almost totally Cs-exchanged samples from various sources with differing Cs contents. They show that over the 0.7 to 4 Cs/uc range all the individual Cs populations vary linearly as a function of total Cs/uc present. At higher total Cs/uc content (4 to approximately 7 Cs/uc) solely Cs1 continues to do so. For Cs2+Cs2' and Cs3+Cs3', the variation is almost linear over the whole concentration range. Computer simulations using a 6-exp-1 Buckingham-type atom-atom van der Waals interaction model yield six possible Cs sites in the actual Cs6.6MFI framework structure. Four of them lie very close to those determined from difference Fourier maps using the room temperature data. A fifth one is close to the Cs2' species after thermal migration at 450 degrees C, and the sixth one is close to the center of the channel intersection. However, this latter site is observed experimentally only in the case of hydrated CsMFI phases. In the anhydrous Cs6.6MFI phase at room temperature, the shortest Cs-framework oxygen distance is Cs3'-O25 = 3.08 A, and the next shortest distances are Cs1-O26 = 3.37, Cs2-O11 = 3.34, Cs2'-O22 = 3.47, and Cs3-O20 = 3.34 A. The framework T(Si,Al) sites most involved in these contacts are the T9, T11, T12, T10, and T3 sites. This implies that these sites are prime candidates for Si/Al substitution.

Journal Article↗

Structural analysis of compartmental models for the hepatic kinetics of drugs.

The structure of some compartmental models for the analysis of the hepatobiliary kinetics of bromosulphalein (BSP) was studied in order to evaluate their adequacy in the estimation of the processes involved in the hepatic metabolism of drugs, namely uptake, conugation, and biliary excretion. Biological measurements were obtained from 4 cholecystectomized patients with a biliary T-tube. Blood and bile specimens were taken at various intervals after the administration of a single intravenous dose of BSP and analyzed for both direct BSP quantitation and chromatographic separation and estimation of BSP metabolic fractions. The structural analysis was carried out by using a mathematical model that described the kinetics of BSP. By means of computer simulations different measurement situations were analyzed, showing for each experimental condition the available information and the degree of accuracy of each estimated parameter. The obtained results show that the use of compartmental models can provide a useful theoretical framework by which the experimental data can be interpreted for the evaluation of the hepatobiliary metabolism and for a discriminant analysis between different physiopathological conditions.

Bile↗

HyBrow: a prototype system for computer-aided hypothesis evaluation.

MOTIVATION: Experimental design, hypothesis-testing and model-building in the current data-rich environment require the biologists' to collect, evaluate and integrate large amounts of information of many disparate kinds. Developing a unified framework for the representation and conceptual integration of biological data and processes is a major challenge in bioinformatics because of the variety of available data and the different levels of detail at which biological processes can be considered. RESULTS: We have developed the HyBrow (Hypothesis Browser) system as a prototype bioinformatics tool for designing hypotheses and evaluating them for consistency with existing knowledge. HyBrow consists of a modeling framework with the ability to accommodate diverse biological information sources, an event-based ontology for representing biological processes at different levels of detail, a database to query information in the ontology and programs to perform hypothesis design and evaluation. We demonstrate the HyBrow prototype using the galactose gene network in Saccharomyces cerevisiae as our test system, and evaluate alternative hypotheses for consistency with stored information. AVAILABILITY: www.hybrow.org

Computational Biology↗

Neural networks in astronomy.

In the last decade, the use of neural networks (NN) and of other soft computing methods has begun to spread also in the astronomical community which, due to the required accuracy of the measurements, is usually reluctant to use automatic tools to perform even the most common tasks of data reduction and data mining. The federation of heterogeneous large astronomical databases which is foreseen in the framework of the astrophysical virtual observatory and national virtual observatory projects, is, however, posing unprecedented data mining and visualization problems which will find a rather natural and user friendly answer in artificial intelligence tools based on NNs, fuzzy sets or genetic algorithms. This review is aimed to both astronomers (who often have little knowledge of the methodological background) and computer scientists (who often know little about potentially interesting applications), and therefore will be structured as follows: after giving a short introduction to the subject, we shall summarize the methodological background and focus our attention on some of the most interesting fields of application, namely: object extraction and classification, time series analysis, noise identification, and data mining. Most of the original work described in the paper has been performed in the framework of the AstroNeural collaboration (Napoli-Salerno).

Astronomy↗

The Aggregated Gut Viral Catalogue (AVrC): A unified resource for exploring the viral diversity of the human gut.

The growing interest in the role of the gut virome in human health and disease, has led to several recent large-scale viral catalogue projects mining human gut metagenomes each using varied computational tools and quality control criteria. Importantly, there has been to date no consistent comparison of these catalogues' quality, diversity, and overlap. In this project, we therefore systematically surveyed nine previously published human gut viral catalogues. While these catalogues collectively screened >40,000 human fecal metagenomes, 82% of the recovered 345,613 viral sequences were unique to one catalogue, highlighting limited redundancy between the ressources and suggesting the need for an aggregated resource bringing these viral sequences together. We further expanded these viral catalogues by mining 7,867 infant gut metagenomes from 12 large-scale infant studies collected in 9 different countries. From these datasets, we constructed the Aggregated Gut Viral Catalogue (AVrC), a unified modular resource containing 1,018,941 dereplicated viral sequences (449,859 species-level vOTUs). Using computational inference tools, annotations were obtained for each vOTU representative sequence quality, viral taxonomy, predicted viral lifestyle, and putative host. This project aims to facilitate the reuse of previously published viral catalogues by the research community and follows a modular framework to enable future expansions as novel data becomes available.

Humans↗

Working towards a national health information system in Australia.

One of the major administrative dilemmas facing the Australian national health care system is the need to reform practices associated with massive data-information overload. The current system is burdened with paper-based administrative forms, patient record files, referral notes and other manual methods of data organisation. An integrated computer-based information system may be perceived as an attractive solution to such burdens. However, computerisation must not be seen as a panacea with the possibility of exacerbating information overload and accentuating privacy concerns. Recent surveys in Australia [1] and the US [2] indicate a perceived causal link between computers and privacy invasion. Any moves toward a national health information system must counter this perception through macro-level education schemes of affected parties and micro-level mechanisms such as the establishment of hospital privacy officers. Such concerns may be viewed as a subset of the wider privacy debate, and information policy development should address such considerations to develop policies to prevent unauthorized access to personal information and to avoid the extraction and sale of sensitive health data. Conservative in nature and slow to change the health care sector may be forced to adopt more efficient work practices through the increasing proliferation of information technology (IT) in health care delivery and an escalating emphasis upon accountability and efficiency of the public health care dollar. The economic rationalist stance taken by governments in Australia and other nations generally will also force health care workers to adopt and develop more efficient information management practices, health indicators and best practice care methods than presently employed by this sector The benefits of a national health information system are far reaching, particularly in developing a more effective health care system through better identifying and understanding community health care trends and in applying IT to the efficient collection of data for the development of more appropriate performance measures and statistical indicators. A coherent and integrated approach is called for in the design of a national health information system which incorporates the necessary and requisite security features to meet privacy concerns. Protecting information privacy poses complex political, economic, technological, legal and social problems for systems developers and health care providers alike [2]. According to Brannigan [3] there are three components involved in the formulation and implementation of privacy: public policy (What level of privacy does society want?); legal structure (Does the law adequately provide for society's privacy requirements?); and technical (how much privacy can technical tools provide, at what cost, and with what effects on the system?). Examining technical tools alone, it is apparent that the necessary technologies are available in Australia to provide the security of medical records required by public policy. Such tools may include encryption, user and data authentication methods, authorisation schemes and mechanisms for the prevention of data inference. While none of these available measures are infallible, it is suitable for most applications where the encryption mechanism can provide protection for a given length of time. Australia needs to develop a coherent national health information infrastructure policy to ultimately avoid fragmented, duplicated and incompatible systems that rely on different standards and protocols. Such a policy will only work by addressing the key issue of patient privacy within a technological framework. The application of IT to health care systems is a sensitive social experiment affecting many professions including general practitioners, medical administrators, politicians, lawyers, computer specialists, privacy advocates and patients whose records will ultimately reside in the system. (abstract trun

Australia↗

Privacy and confidentiality of patient information. Challenges for nursing.

The growing interest in automating healthcare information and the emergence of the computer-based patient record-keeping have brought the issues of privacy and confidentiality to the fore-front. Nurse executives and nurse managers need to be sensitive to these issues, as never before, to guide their staffs and to prevent harm. Technology makes sensitive information more accessible to more people, with resulting benefits and dangers. The author presents a nursing ethical framework for discussing patient privacy and confidentiality issues, and highlights specific issues that reflect nursing's unique viewpoints.

Codes of Ethics↗

Distributed data mining on grids: services, tools, and applications.

Data mining algorithms are widely used today for the analysis of large corporate and scientific datasets stored in databases and data archives. Industry, science, and commerce fields often need to analyze very large datasets maintained over geographically distributed sites by using the computational power of distributed and parallel systems. The grid can play a significant role in providing an effective computational support for distributed knowledge discovery applications. For the development of data mining applications on grids we designed a system called Knowledge Grid. This paper describes the Knowledge Grid framework and presents the toolset provided by the Knowledge Grid for implementing distributed knowledge discovery. The paper discusses how to design and implement data mining applications by using the Knowledge Grid tools starting from searching grid resources, composing software and data components, and executing the resulting data mining process on a grid. Some performance results are also discussed.

Algorithms↗

Robustness of a computer-assisted diabetes self-management intervention across patient characteristics, healthcare settings, and intervention staff.

BACKGROUND: A major problem in the dissemination of most interventions found to be efficacious is that they are of limited or unknown generalizability. OBJECTIVE: To document the "robustness," or external validity, of a computer-assisted diabetes self-management program across different patient characteristics, healthcare settings (mixed payer vs health maintenance organization), intervention staff, and outcomes. STUDY DESIGN: A randomized controlled trial evaluating a computer-assisted behavior change program for adult patients with type 2 diabetes mellitus (n = 217) vs a computerized health risk assessment. METHODS: Outcomes were identified using the RE-AIM framework and included program adoption among physicians, reach across patient groups, implementation, and behavioral (fat intake and physical activity) and biological (glycosylated hemoglobin and lipid levels) effectiveness measures. RESULTS: The program achieved 41% patient participation, variable adoption across healthcare settings (76% of health maintenance organization physicians vs 18% of non-health maintenance organization physicians participated), good implementation, and improvement in behavioral outcomes. There were few significant interactions between treatment condition and patient characteristics, type of healthcare setting, or interventionist experience on effectiveness measures. CONCLUSIONS: Patients and physicians were willing to participate in a computer-assisted dietary and physical activity goal-setting intervention, although participation varied by healthcare setting. Interventionists from different backgrounds successfully delivered the intervention, and the results appear robust across various patient and delivery characteristics.

Aged↗

A mathematical model of the human body in health, disease, and during treatment.

This paper presents a preliminary description of a mathematical model of the human body and some details of the computer software and hardware used to study the model. The model includes many organ systems of the body and the interplay among systems. In addition to this physiological framework, a variety of diseases and therapeutic measures can be simulated. The model can be used in two different ways. In one mode, hypothetical experiments can be conducted that focus on the underlying physiological mechanisms and the complex interaction among organ systems that are essential to the maintenance of life. In a second mode, clinical encounters can be simulated in which hypothetical patients are seen, diagnosed and treated.

Acid-Base Equilibrium↗

Mercury toxicokinetics in Wistar rats exposed to elemental mercury vapour: modeling and computer simulation.

The kinetics of total mercury (Hg) absorption, distribution and elimination in Wistar rats exposed for long periods to elemental mercury vapour (Hg zero) in the Idrija mercury mine were studied. From the experimental data base a compartmental model was built as a framework for experimental data interpretation and prediction of organ mercury levels under different conditions. Using the model the exposures of rats under conditions comparable to those of professionally exposed workers (mercury miners, workers in the chloralkali industry) and individuals with amalgam fillings were simulated.

Animals↗

Reconciling repertoire shift with affinity maturation: the role of deleterious mutations.

The shift in Ab repertoire, from Abs dominating certain primary B cell responses to genetically unrelated Abs dominating subsequent "memory" responses, challenges the accepted paradigm of affinity maturation. We used mathematical modeling and computer simulations of the dynamics of B cell responses, hypermutation, selection, and memory cell formation to test hypotheses attempting to explain repertoire shift. We show that repertoire shift can be explained within the framework of the affinity maturation paradigm, only when we recognize the destructive nature of hypermutation: B cells with a high initial affinity for the Ag are less likely to improve through random mutations.

Antibody Affinity↗

Genepi: a blackboard framework for genome annotation.

BACKGROUND: Genome annotation can be viewed as an incremental, cooperative, data-driven, knowledge-based process that involves multiple methods to predict gene locations and structures. This process might have to be executed more than once and might be subjected to several revisions as the biological (new data) or methodological (new methods) knowledge evolves. In this context, although a lot of annotation platforms already exist, there is still a strong need for computer systems which take in charge, not only the primary annotation, but also the update and advance of the associated knowledge. In this paper, we propose to adopt a blackboard architecture for designing such a system RESULTS: We have implemented a blackboard framework (called Genepi) for developing automatic annotation systems. The system is not bound to any specific annotation strategy. Instead, the user will specify a blackboard structure in a configuration file and the system will instantiate and run this particular annotation strategy. The characteristics of this framework are presented and discussed. Specific adaptations to the classical blackboard architecture have been required, such as the description of the activation patterns of the knowledge sources by using an extended set of Allen's temporal relations. Although the system is robust enough to be used on real-size applications, it is of primary use to bioinformatics researchers who want to experiment with blackboard architectures. CONCLUSION: In the context of genome annotation, blackboards have several interesting features related to the way methodological and biological knowledge can be updated. They can readily handle the cooperative (several methods are implied) and opportunistic (the flow of execution depends on the state of our knowledge) aspects of the annotation process.

Algorithms↗

Systematic Dissection of Key Driver Perturbation Signatures in Single Cells via ECCITE-seq.

CRISPR screens, such as expanded CRISPR-compatible cellular indexing of transcriptomes and epitopes by sequencing (ECCITE-seq), enable the simultaneous measurement of transcriptomes, gRNA identity, and cell-surface protein expression at single-cell resolution to systematically interrogate gene function. This platform provides a powerful and scalable experimental approach for validating disease-associated regulators identified by large-scale association studies and other computational methods, including network-based analyses of multi-omics data. Here, as an example application, we describe an ECCITE-seq framework to characterize the transcriptomic consequences of perturbing multiple neuronal key driver genes associated with Alzheimer's disease (AD) in human-induced pluripotent stem cell (hiPSC)-derived neurons. More broadly, by integrating customized pooled gRNA libraries with different CRISPR effectors across multiple cell types, this approach allows for the assessment of the regulatory impact of candidate genes implicated in development and disease processes.

Humans↗