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At least 1,009 records · Page 56Linked to original sources
PubMed2004

Predicting shifts in dynamics of cannibalistic field populations using individual-based models.

The occurrence of qualitative shifts in population dynamical regimes has long been the focus of population biologists. Nonlinear ecological models predict that these shifts in dynamical regimes may occur as a result of parameter shifts, but unambiguous empirical evidence is largely restricted to laboratory populations. We used an individual-based modelling approach to predict dynamical shifts in field fish populations where the capacity to cannibalize differed between species. Model-generated individual growth trajectories that reflect different population dynamics were confronted with empirically observed growth trajectories, showing that our ordering and quantitative estimates of the different cannibalistic species in terms of life-history characteristics led to correct qualitative predictions of their dynamics.

Animals↗
PubMed2002

Three-dimensional common-feature hypotheses for octopamine agonist 2-(arylimino)imidazolidines.

Three-dimensional pharmacophore hypotheses were built from a set of 10 octopamine (OA) agonist 2-(Arylimino)imidazolidines (AIIs), 2-(Arylimino)thiazolidines (AITs) and 2-(Arylimino)oxazolidines (AIOs). Among the 10 common-featured models generated by program Catalyst/HipHop, a hypothesis including a ring aromatic (RA), a positive ionizable (PI) and three hydrophobic aliphatic (HpAl) features was considered to be important in evaluating the OA-agonist activity. Active OA agonist 2,6-Et2 AII mapped well onto all the RA, PI and HpAl features of the hypothesis. On the other hand, less active compounds were shown to be difficult to achieve the energetically favorable conformation which is found in the active molecules in order to fit the 3-D common-feature pharmacophore models. Taken together, 2,6-Et2-Ph and foramidine structures are important as OA agonists. The present studies on OA agonists demonstrate that a RA, a PI and three HpAl sites located on the molecule seem to be essential for OA-agonist activity.

Animals↗
PubMed1987

Simulation of genetic control of reproduction in beef cows. III. Within-herd breeding value estimation with known breeding dates.

Procedures for breeding value estimation for reproductive traits with known breeding dates were developed and tested using results of a computer simulation model of genetic control of bovine reproduction. The model generated realized reproductive outputs as a function of underlying genetic variation in two independent traits: conception rate (CR), which was indicative of the ability to conceive given estrus, and PPI, the postpartum interval from calving to first estrus. Two scenarios were considered. In the first, all cows were assumed to be cycling at the start of breeding and to be bred artificially. For this scenario, breeding values for CR could be estimated from information on observed breeding and calving dates by using a categorical trait, multi-stage selection model. Breeding value estimation for PPI, however, required actual measurement of PPI because if PPI and CR are genetically independent and if all cows are cycling at the beginning of breeding, subsequent breeding and calving dates are independent of PPI. The second scenario recognized that not all females would be cycling at the start of breeding. For this scenario, the categorical trait, multi-stage selection model could still be applied for breeding value estimation for CR, but accumulation of data across years was complicated by a need to consider the lifetime reproductive pattern of the individual rather than just the sum of each year's performances. Breeding value estimates for PPI could be obtained from observed breeding and calving dates for this scenario, but required consideration of the distributional properties of PPI.

Animals↗
PubMed2006

Virtual cystoscopy--a surgical planning and guidance tool.

Image guided-surgery systems facilitates surgical planning phases of endoscopic procedures. In this paper, we used a software package for 3D surface model generation and vizualization of the urinary bladder, based on magnetic resonance (MR) cross sectional images of the pelvis. The patients group consisted in 6 patients diagnosed with urinary bladder tumour. They were submitted to MRI exam. Twelve consecutive cross sectional images of the pelvis were aquired (TR (repetition time) = 600 msec, TE (echo time) = 19 msec, slice thickness = 6 divided by 7 mm, FOV (field of view) = 36 cm. All these images were transferred to a personal computer running the 3DSlicer software. We obtained, for each patient, a 3D model of the pelvis including the urinary bladder. In This way, the surgical enviroment was simulated and we are able to investigate the bladder by virtual cystoscopy. The virtual endoscopy may be used as a tool in the preoperative training and in surgical planning.

Cystoscopy↗
PubMed1996

Measurement and modeling of thermal transients during Er:YAG laser irradiation of vitreous.

BACKGROUND AND OBJECTIVE: We investigated the transient thermal behavior of vitreous in order to understand the local thermal effects of laser output, and to predict the potential for unintentional injury during Er:YAG laser vitreoretinal surgery. STUDY DESIGN/MATERIALS AND METHODS: The output of a free-running Er:YAG laser (2.94 microns, 300 microseconds FWHM) was delivered through a fiberoptic and applied to en bloc samples of bovine vitreous. Temperature was measured with ultrafine thermocouples. RESULTS: For 6 mJ pulse energy at 10 Hz, a temperature rise of 20 degrees C is measured 500 microns from the laser tip. The temperature rise is localized with a rapid fall-off greater than 1 mm from the energy source. At constant time-averaged laser power, the temperature profile is independent of repetition rate. Our finite-difference model generates results qualitatively consistent with measured data and allows for investigation of the influence of thermophysical parameters on heat transfer. CONCLUSION: Thermal injury to ocular structures should be limited during intravitreal application of Er:YAG laser energy.

Animals↗
PubMed1997

Joint kinematics simulation from medical imaging data.

A method for joint kinematics simulation is described. Kinematics parameters are determined from the relative displacement of marker sets placed on anatomical landmarks of surface models generated from medical imaging contour data. The landmarks are identified manually on fingers in multiple positions. A mathematical algorithm was then used to ascertain the kinematics axes of motion of the fingers. Once these axes are located, they are used as the base of a real time interactive simulation of the finger. The entire simulation was accomplished in a high-resolution graphics environment. A full complement of interactive tools (virtual dials and buttons controlled via mouse) was used to enhance the user interface. The development of the system, the model and the advantages and disadvantages of the method are discussed.

Arthrography↗
PubMed1989

PPS-87: a new event oriented solar proton prediction model.

A new event-oriented solar proton prediction model has been developed and implemented at the USAF Space Environment forecast facility. This new model generates predicted solar proton time-intensity profiles for a number of user adjustable energy ranges and is also capable of making predictions for the heavy ion flux. The computer program is designed so a forecaster can select inputs based on the data available in near real-time at the forecast center as the solar flare is occurring. The predicted event amplitude is based on the electromagnetic emission parameters of the solar flare (either microwave or soft X-ray emission) and the solar flare position on the sun. The model also has an update capability where the forecaster can normalize the prediction to actual spacecraft observations of spectral slope and particle flux as the event is occurring in order to more accurately predict the future time-intensity profile of the solar particle flux. Besides containing improvements in the accuracy of the predicted energetic particle event onset time and magnitude, the new model converts the predicted solar particle flux into an expected radiation dose that might be experienced by an astronaut during EVA activities or inside the space shuttle.

Computer Simulation↗
PubMed2005

R-state hemoglobin bound to heterotropic effectors: models of the DPG, IHP and RSR13 binding sites.

We performed a docking study followed by a 500-ps molecular dynamics simulation of R-state human adult hemoglobin (HbA) complexed to different heterotropic effectors [2,3-diphosphoglycerate (DPG), inositol hexaphosphate (IHP), and 2-[4-[(3,5-dichlorophenylcarbamoyl)-]methyl]-phenoxy]-2-methylpropionic acid (RSR13)) to propose a molecular basis for recently reported interactions of effectors with oxygenated hemoglobin. The simulations were carried out with counterions and explicit solvation. As reported for T-state HbA, the effector binding sites are also located in the central cavity of the R-state and differ depending on effector anionic character. DPG and IHP bind between the alpha-subunits and the RSR13 site spans the alpha1-, alpha2- and beta2-subunits. The generated models provide the first report of the molecular details of R-state HbA bound to heterotropic effectors.

Aniline Compounds↗
PubMed2006

Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease.

Transgenic mice carrying disease-linked forms of genes associated with Alzheimer disease often demonstrate deposition of the beta-amyloid as senile plaques and cerebral amyloid angiopathy. We have characterized the natural history of beta-amyloid deposition in APPswe/PS1dE9 mice, a particularly aggressive transgenic mouse model generated with mutant transgenes for APP (APPswe: KM594/5NL) and PS1 (dE9: deletion of exon 9). Ex vivo histochemistry showed Abeta deposition by 4 months with a progressive increase in plaque number up to 12 months and a similar increase of Abeta levels. In vivo multiphoton microscopy at weekly intervals showed increasing beta-amyloid deposition as CAA and plaques. Although first appearing at an early age, CAA progressed at a significantly slower rate than in the Tg2576 mice. The consistent and early onset of beta-amyloid accumulation in the APPswe/PS1dE9 model confirms its utility for studies of biochemical and pathological mechanisms underlying beta-amyloid deposition, as well as exploring new therapeutic treatments.

Age Factors↗
PubMed2005

The posterior probability of linkage allowing for linkage disequilibrium and a new estimate of disequilibrium between a trait and a marker.

The posterior probability of linkage (PPL) statistic has been developed as a method for the rigorous accumulation of evidence for or against linkage allowing for both intra- and inter-sample heterogeneity. To date, the method has assumed linkage equilibrium between alleles at the trait locus and the marker locus. We now generalize the PPL to allow for linkage disequilibrium (LD), by incorporating variable phase probabilities into the underlying linkage likelihood. This enables us to recover the marginal posterior density of the recombination fraction, integrating out nuisance parameters of the trait model, including the locus heterogeneity (admixture) parameter, as well as a vector of LD parameters. The marginal posterior density can then be updated across data subsets or new data as they become available, while allowing parameters of the trait model to vary between data sets. The method applies immediately to general pedigree structures and to markers with multiple alleles. In the case of SNPs, the likelihood is parameterized in terms of the standard single LD parameter D'; and it therefore affords a mechanism for estimation of D' between the marker and the trait, again, without fixing the parameters of the trait model and allowing for updating across data sets. It is even possible to allow for a different associated allele in different populations, while accumulating information regarding the strength of LD. While a computationally efficient implementation for multi-allelic markers is still in progress, we have implemented a version of this new LD-PPL for SNPs and evaluated its performance in nuclear families. Our simulations show that LD-PPLs tend to be larger than PPLs (stronger evidence in favor of linkage/LD) with increased LD level, under a variety of generating models; while in the absence of linkage and LD, LD-PPLs tend to be smaller than PPLs (stronger evidence against linkage). The estimate of D' also behaves well even in relatively small, heterogeneous samples.

Genes, Dominant↗
PubMed1997

Molecular modelling of cytochrome P4502D6 (CYP2D6) based on an alignment with CYP102: structural studies on specific CYP2D6 substrate metabolism.

1. A molecular model of CYP2D6 has been constructed from the bacterial form CYP102 via a homology alignment between the CYP2D subfamily and CYP102 protein sequences. 2. A number of typical CYP2D6 substrates are shown to fit the putative active site of the enzyme, as can the specific inhibitor quinidine. 3. Some of the allelic variants in CYP2D6, which give rise to genetic polymorphisms in 2D6-mediated metabolism, can be rationalized in terms of their position within the active site region. 4. The results of site-directed mutagenesis experiments are consistent with the CYP2D6 model generated from the CYP102 crystal structure. 5. The possibility of an alternative orientation within the active site may explain the CYP2D6-mediated metabolism of relatively large-sized substrates.

Alleles↗
PubMed2004

Analysis and validation of a predictive model for growth and death of Aeromonas hydrophila under modified atmospheres at refrigeration temperatures.

Specific growth and death rates of Aeromonas hydrophila were measured in laboratory media under various combinations of temperature, pH, and percent CO(2) and O(2) in the atmosphere. Predictive models were developed from the data and validated by means of observations obtained from (i) seafood experiments set up for this purpose and (ii) the ComBase database (http://www.combase.cc; http://wyndmoor.arserrc.gov/combase/). Two main reasons were identified for the differences between the predicted and observed growth in food: they were the variability of the growth rates in food and the bias of the model predictions when applied to food environments. A statistical method is presented to quantitatively analyze these differences. The method was also used to extend the interpolation region of the model. In this extension, the concept of generalized Z values (C. Pin, G. García de Fernando, J. A. Ordóñez, and J. Baranyi, Food Microbiol. 18:539-545, 2001) played an important role. The extension depended partly on the density of the model-generating observations and partly on the accuracy of extrapolated predictions close to the boundary of the interpolation region. The boundary of the growth region of the organism was also estimated by means of experimental results for growth and death rates.

Aeromonas hydrophila↗
PubMed2001

Mutant and genetically modified mice as models for studying the relationship between aging and carcinogenesis.

Increased interest is emerging in using mouse models to assess the genetics of aging and age-related diseases, including cancer. However, only limited information is available regarding the relationship between aging and spontaneous tumor development in genetically modified mice. Analysis of various transgenic and knockout rodent models with either a shortened or an extended life span, provides a unique opportunity to evaluate interactions of genes involved in the aging process and carcinogenesis. There are only a few models which show life span extension. Ames dwarf mutant mice, p66(-/-) knockout mice, alpha MUPA and MGMT transgenic mice live longer than wild-type strains. The incidence of spontaneous tumors in these mutant mice was usually similar to those in controls, whereas the latent period of tumor development was increased. Practically all models of accelerated aging showed increased incidence and shorter latency of tumors. This phenomenon has been observed in animals which display a phenotype that more closely resembles natural aging, and in animals which manifest only some features of the normal aging process. These observations are in agreement with an earlier established positive correlation between tumor incidence and the rate of tumor incidence increase associated with aging and the aging rate in a population. Thus, genetically modified animals are a valuable tool in unravelling mechanisms underlying aging and cancer. Systemic evaluation of newly generated models should include onco-gerontological studies.

Aging↗
PubMed2003

Three-dimensional pharmacophore hypotheses of octopamine/tyramine agonists which inhibit [1-14C]acetate incorporation in Plodia interpunctella.

Three-dimensional pharmacophore hypotheses were built from a set of 36 octopamine (OA)/tyramine (TA) agonists responsible for the inhibition of sex-pheromone production in Plodia interpunctella. Among the ten chemical-featured models generated by a program Catalyst/Hypo, hypotheses including hydrogen-bond acceptor (HBA), hydrogen-bond acceptor aliphatic (HBAl), hydrophobic (Hp), hydrophobic aromatic (HpAr) and hydrophobic aliphatic (HpAl) features were considered to be important and predictive in evaluating OA/TA agonists. Active agonists mapped well onto all the features of the hypothesis such as HBA, HBAl, Hp, HpAr and HpAl features. On the other hand, inactive compounds were shown to be poorly capable of achieving an energetically favorable conformation shared by the active molecules in order to fit the 3-D chemical-feature pharmacophore models. Those hypotheses are considered to be used in designing new leads for hopefully more active compounds. Further research on the comparison of models from the agonists may help elucidate the mechanisms of OA/TA receptor-ligand interactions.

Acetates↗
PubMed1993

Structure-activity relationships and binding model of novel aromatase inhibitors.

The use of aromatase inhibitors is an established therapy for oestrogen-dependent breast cancer in postmenopausal women. However, the sole commercially available aromatase inhibitor, aminoglutethimide, is not very selective. We have therefore developed fadrozole hydrochloride and CGS 20,267, which are both currently under clinical evaluation. This report will present an analysis of structure-activity relationships in the azole series of inhibitors and give an account of the further optimization of our development compounds, starting from CGS 20,267 over CGP 45,688 and leading to CGP 47,645, the most potent aromatase inhibitor in vivo reported to date. In addition, on the basis of comparisons of these azole-type inhibitors with the most potent steroidal inhibitors published in the literature, we propose a CAMM-generated model describing the relative binding modes of these two classes of compounds at the active site of the enzyme.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Cluster analysis and promoter modelling as bioinformatics tools for the identification of target genes from expression array data.

Expression arrays yield enormous amounts of data linking genes, via their cDNA sequences, to gene expression patterns. This now allows the characterisation of gene expression in normal and diseased tissues, as well as the response of tissues to the application of therapeutic reagents. Expression array data can be analysed with respect to the underlying protein sequences, which facilitates the precise determination of when and where certain groups of genes are expressed. More recent developments of clustering algorithms take additional parameters of the experimental set-up into account, focusing more directly on co-regulated set of genes. However, the information concerning transcriptional regulatory networks responsible for the observed expression patterns is not contained within the cDNA sequences used to generate the arrays. Regulation of expression is determined to a large extent by the promoter sequences of the individual genes (and/or enhancers). The complete sequence of the human genome now provides the molecular basis for the identification of many regulatory regions. Promoter sequences for specific cDNAs can be obtained reliably from genomic sequences by exon mapping. In the many cases in which cDNAs are 5'-incomplete, high quality promoter prediction tools can be used to locate promoters directly in the genomic sequence. Once sufficient numbers of promoter sequences have been obtained, a comparative promoter analysis of the co-regulated genes and groups of genes can be applied in order to generate models describing the higher order levels of transcription factor binding site organisation within these promoter regions. Such modules represent the molecular mechanisms through which regulatory networks influence gene expression, and candidates can be determined solely by bioinformatics. This approach also provides a powerful alternative for elucidating the functional features of genes with no detectable sequence similarity, by linking them to other genes on the basis of their common promoter structures.

Algorithms↗
PubMed2001

Determining trait locus position from multipoint analysis: accuracy and power of three different statistics.

Previous work using two-point linkage analysis showed that performing a lod score (LOD) analysis twice, once assuming dominant and once assuming recessive inheritance, and then taking the larger of the two values (designated MMLS) usually has more power to detect linkage than any other method tested. Using computer simulation for a variety of complex inheritance models, we demonstrated power for the MMLS comparable with analysis assuming the true model. However, reports in the literature suggested that the MMLS approach might fail to detect linkage using multipoint analysis due to genetic model misspecification. Here, we tested the robustness of the MMLS approach under multipoint analysis. We simulated data under complex inheritance models, including heterogeneity, epistatic, and additive models. We examined the expected maximum LOD, LOD assuming heterogeneity (HLOD), and nonparametric linkage statistics and the corresponding estimated position in a chromosomal interval of 10 markers with 10% recombination between markers. The mean estimates of position were generally good for all three statistics except when heterogeneity existed, where the LOD and the NPL did not perform as well as the HLOD. The MMLS approach was as robust using multipoint as using two-point linkage analysis. LOD and/or the HLOD generally had more power to detect linkage than NPL across a variety of generating models, even after correcting for the multiple tests. For finding linkage to one locus of several contributing to disease expression, assuming the dominant and recessive models with reduced penetrance is a good approximation of the mode of inheritance at that locus.

Bias↗
PubMed2002

Confirmatory factor analysis of internet use and addiction.

The ever-changing nature of the Internet continues to fuel questions as to its benefits and possible drawbacks. One issue that is particularly problematic is the validity of claims that the Internet is addictive. The present study used a confirmatory factor analysis (CFA) on a data set of 527 participants using the same survey developed by Pratarelli et al. (1) We propose a theoretical model of the relationship between (1) Internet addiction, (2) a sexual factor, and (3) an Internet use factor. These three factors were tested using two structural equation models generated on LISREL. The CFA revealed that the three factors are not orthogonal to each other, but instead are related to some degree as one would expect if a supposed Internet addicted individual exhibited behaviors related to each factor. We next tested whether the addiction was the causal factor leaving the sex and User factors as endogenous (i.e., resulting from the addiction). The second structural equation tested the contrasting possibility that sex and User related activities were exogenous to the addiction factor (i.e., the addiction resulted from these two activities). The analysis revealed that model 1, where the addiction is the causal factor behind the sex and User factors, had a stronger model fit index. On the basis of these current data it appears that Internet addiction may involve an addictive performance profile which in turn leads to excessive behaviors that involve (1) use of the Internet for sexual purposes and (2) its functional usefulness for a variety of professional and personal goals.

Adolescent↗