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At least 487 records · Page 27Linked to original sources
PubMed1998

Parallel implementations of individual-based models in biology: bulletin- and non-bulletin-board approaches.

Particle-based models are simulations in which the discrete representation of physical phenomenon involves interacting particles. This paper studies the efficiency of two different methods of implementing these models on a network of UNIX workstations. Two data parallel methods of modeling particles are tested: bulletin-board and non-bulletin-board. In the former method, the programs communicate through a logically shared, associative memory called a bulletin-board. The simulated particles are distributed among the workstations dynamically as the processing load on the processors changes. In the latter method, the particles are divided amongst the networked workstations statically at load time. The simulated system is a collection of ants moving and foraging in a two-dimensional space. This paper analyzes and compares the execution times of both implementations for different combinations of particles and number of workstation, using speed-up, tuple granularity and communication cost as measures. Analysis shows that the bulletin-board method is better for particle-based simulations when the correct granularity is chosen.

Animals↗
PubMed1988

Immunohistochemical localization of monoamines and cyclic nucleotides. Their application in quantitative immunofluorescence studies and tracing monoaminergic neuronal connections.

We have described immunocytochemical methods for the direct visualization of monoamine- and cGMP-containing neurons, using antibodies to the primary or secondary messengers themselves. The specificity and affinity of these antibodies were determined using quantitative immunofluorescence of gelatin models, as non-biological models, to which the native substances and their possibly cross-reacting compounds were incorporated. The use of retro- and anterograde tracers both in conjunction with immunohistochemical procedures provides the possibility to characterize transmitter specifically afferent and efferent pathways. With the presented double-label immunocytochemical procedures it is feasible to visualize and trace a projection between two brain areas, and in addition to specify the transmitters which are involved in their afferents and efferents and their target neurons and neurons of origin. Using the SCG, as a biological model, we could demonstrate that cGMP levels in individual cells could be elevated by cholinergic agonists. Moreover, using quantitative immunofluorescence of cGMP as a post- or presynaptic marker we have the possibility to measure the post-/presynaptic effects of monoamines or neuropeptides in individual neurons.

Animals↗
PubMed1980

13C-NMR detection of lipid polymorphism in model and biological membranes.

1. The application of the 13C-NMR technique to the study of lipid polymorphism is described for various model and biological membranes. 2. The 13-C-NMR line-width of various resonances of the lipid molecule and sensitive to the bilayer in equilibrium hexagonal and the bilayer in equilibrium 'isotropic' phase transition. The latter transition in some cases is accompanied by the occurrence of lipidic particles as detected by freeze-fracturing. Thus, specific 13C-labeling experiments allow the study of the individual phase behaviour of lipids in mixed lipid systems. 3. In diet experiments using rats, the choline group of phosphatidylcholine present in erythrocyte, endoplasmic and sarcoplasmic reticulum membranes could be specifically 13C-labeled. The 13C line-widths of the resonance from the erythrocyte are typical for a lamellar arrangement of the membrane lipids. In strong contrast, the line-width observed at 37 degree C for the endoplasmic and sarcoplasmic reticulum membranes is much smaller, typical of the isotropic phases observed in model membranes. In isolated rat liver microsomes and liver slices, the 13C line-width is strongly temperature dependent. At lower temperatures the line-widths strongly increase towards values typical of lipids in a bilayer structure.

Animals↗
PubMed1979

Homografts of the middle ear. Privileged tissue or privileged site.

To explain the survival and behavior of homografts, we have tried, by means of discussion and use of biological models, to resolve a problem with three unknowns, ie, the tympanic membrane, the ossicle, and the middle ear, with the notions of privileged tissue and privileged site. The tympanic membrane survives because of the relative stability of its fibers and the absence of mechanical trauma. Later, the membrane is sheathed by fibrous tissue. The ossicle is not only tolerated by the host but is also invaded and ossified.

Ear Ossicles↗
PubMed2004

Mapping structural brain alterations in obsessive-compulsive disorder.

BACKGROUND: Recent technical developments have made it feasible to comprehensively assess brain anatomy in psychiatric populations. OBJECTIVE: To describe the structural brain alterations detected in the magnetic resonance images of a large series of patients with obsessive-compulsive disorder (OCD) using imaging procedures that allow the evaluation of volume changes throughout the brain. DESIGN: Case-control study. SETTING: Referral OCD unit in a tertiary hospital. PARTICIPANTS: A consecutive sample of 72 outpatients with OCD and 72 age- and sex-matched control subjects. INTERVENTIONS: Three-dimensional sequences were obtained in all participants. A statistical parametric mapping approach was used to delineate possible anatomical alterations in the entire brain. To preserve volumetric information, voxel values were modulated by the Jacobian determinants (volume change measurement) derived from spatial normalization. MAIN OUTCOME MEASURES: Voxelwise brain volumes. RESULTS: The brains of patients with OCD showed reduced gray matter volume in the medial frontal gyrus, the medial orbitofrontal cortex, and the left insulo-opercular region. A relative increase in gray matter volume was observed bilaterally in the ventral part of the putamen and in the anterior cerebellum. All these brain alterations were abnormally correlated in patients with OCD, and age statistically significantly contributed to the relative enlargement observed in the striatal areas. Disease severity, the nature of symptoms, and comorbidities were not related to the changes described. Nevertheless, patients with prominent aggressive obsessions and checking compulsions showed reduced amygdala volume in the right hemisphere. CONCLUSIONS: The pattern of anatomical features depicted by this voxelwise approach is consistent with data from functional studies. The reported anatomical maps identified the specific parts of the frontostriatal system that were altered in patients with OCD and detected changes in anatomically connected distant regions. These data further define the structural brain alterations in OCD and may contribute to constraining the prevailing biological models of this psychiatric process.

Adolescent↗
PubMed2003

Glutamylated tubulin: diversity of expression and distribution of isoforms.

Glutamylation of alpha and beta tubulin isotypes is a major posttranslational modification giving rise to diversified isoforms occurring mainly in neurotubules, centrioles, and axonemes. Monoglutamylated tubulin isoforms can be differentially recognized by two mAbs, B3 and GT335, which both recognize either polyglutamylated isoforms. In the present study, immunoelectron microscopy and immunofluorescence analyses were performed with these two mAbs to determine the expression and distribution of glutamylated tubulin isoforms in selected biological models whose tubulin isotypes are characterized. In mouse spermatozoa, microtubules of the flagellum contain polyglutamylated isoforms except in the tip where only monoglutamylated isoforms are detected. In spermatids, only a subset of manchette microtubules contain monoglutamylated tubulin isoforms. Cytoplasmic microtubules of Sertoli cells are monoglutamylated. Mitotic and meiotic spindles of germ cells are monoglutamylated whereas the HeLa cell mitotic spindle is polyglutamylated. Three models of axonemes are demonstrated as a function of the degree and extent of tubulin glutamylation. In lung ciliated cells, axonemes are uniformly polyglutamylated. In sea urchin sperm and Chlamydomonas, flagellar microtubules are polyglutamylated in their proximal part and monoglutamylated in their distal part. In Paramecium, cilia are bi- or monoglutamylated only at their base. In all cells, centrioles or basal bodies are polyglutamylated. These new data emphasize the importance of glutamylation in all types of microtubules and strengthen the hypothesis of its role in the regulation of the intracellular traffic and flagellar motility.

Animals↗
PubMed2005

Differential proteome analysis of conditioned media to detect Smad4 regulated secreted biomarkers in colon cancer.

Smad4 is a tumor suppressor gene primarily involved in carcinogenesis of the pancreas and colon. The functional inactivation of Smad4 is a late step genetically. In pancreatic carcinogenesis, loss of Smad4 marks the transition to invasive growth. In colorectal cancers, the frequency of Smad4 inactivation is markedly increased in metastatic cancers. We have established cell biological models, re-expressing Smad4 in deficient human cancer cells, in which we could show that Smad4 is adequate to suppress tumor growth through suppression of angiogenic and invasive properties. Thus, pairs of Smad4-re-expressing and Smad4-deficient cells are prone to model the progression from premalignant stages to carcinomas in the carcinogenic process and may provide access to Smad4 targets of high clinical relevance. We present here a "differential secretome analysis", comparing all the proteins released in vitro from the Smad4-deficient and Smad4-re-expressing SW480 human colon carcinoma cells. The differential secretome catalog comprises more than 25 proteins including proteases and protease inhibitors, as well as established tumor biomarkers. In conclusion, this approach proved to be a sensitive tool to specifically detect Smad4 targets relevant for tumor-stroma interactions. It is also able to reflect complex alterations of cellular physiology. Moreover, the results support our hypothesis that human tumor markers detectable in serum may be identified through differential secretome analyses.

Biomarkers, Tumor↗
PubMed2003

Exploring heterogeneity in tumour data using Markov chain Monte Carlo.

We describe a Bayesian approach to incorporate between-individual heterogeneity associated with parameters of complicated biological models. We emphasize the use of the Markov chain Monte Carlo (MCMC) method in this context and demonstrate the implementation and use of MCMC by analysis of simulated overdispersed Poisson counts and by analysis of an experimental data set on preneoplastic liver lesions (their number and sizes) in the presence of heterogeneity. These examples show that MCMC-based estimates, derived from the posterior distribution with uniform priors, may agree well with maximum likelihood estimates (if available). However, with heterogeneous parameters, maximum likelihood estimates can be difficult to obtain, involving many integrations. In this case, the MCMC method offers substantial computational advantages.

Animals↗
PubMed1995

Cellular segregation and engulfment simulations using the cell programming language.

In developmental biology, modeling and simulation play an important role in understanding cellular interactions. In this paper a simple language, the Cell Programming Language (CPL), is suggested for writing programs that describe this behavior. Using these programs, it is possible to simulate and visualize intercellular behavior. CPL is used to model cellular segregation based upon the differential adhesion hypothesis. Results indicate that a high degree of segregation can be produced in a mixture of cells by allowing random motion. The engulfment of a tissue by a less adhesive tissue is also observed when the two tissues are placed in contact. Both these simulations utilize only local interactions and random motion of cells. Earlier simulations used long-range interactions to observe similar effects. The present simulations prove that random motion of cells can produce long-range effects.

Animals↗
PubMed1988

Kinetic studies on nitrite and nitrate in rats by ion-pair chromatography.

A highly sensitive and specific ion-pair chromatographic method is presented for the simultaneous determination of nitrite (NO2-) and nitrate (NO3-) in plasma. The detection limits are 2 mumol NO2-/l and 8 mumol NO3-/l with recovery rates of 98-99%. The applicability of this method to clinical medicine is demonstrated using NO2- -loaded rats as a biological model: following intravenous infusion or intragastric application of NO2-, blood levels of NO2-, NO3- and methemoglobin are measured during 2-64 min. The kinetic data obtained reflect the complex metabolism of NO2- and NO3- in living organisms.

Animals↗
PubMed1984

Thermally defined cryomicroscopy and thermodynamic analysis in lymphocyte freezing.

A cryomicroscope is described which provides the possibility of quantifying the volume loss of cells during freezing, detection of intracellular ice formation during cooling and warming, as well as the determination of viability as function of (constant) cooling rates. The basic mechanisms occurring in cryopreservation have been studied with this system using the human lymphocyte suspended in pure saline as a biological model system; experimentally observed exosmosis during freezing is compared to predictions from a thermodynamic model. Cell volume loss during freezing has been determined experimentally for cooling rates of 2.4, 12, 48, and 120 degrees K/min. Exosmosis also was calculated corresponding to various assumptions regarding the concentration dependence of the hydraulic permeability of the cells. Further calculations of exosmosis are performed for determining the effects of the initial cell volume. The temperatures and transition cooling rate ranges of intracellular ice formation have been determined. On the basis of exosmosis and a lethal level of intracellular salt concentration, a hypothetical relative optimum of the cooling rate is theoretically predicted and compared to the experiments.

Blood Preservation↗
PubMed1993

The female longevity phenomenon. Hypotheses on some molecular and cell biology aspects.

The most relevant theories on the sex-dependent longevity at population level are critically re-examined in the light of the knowledge available today on the aging process at cellular and molecular level. The aim of this perspective is to help in the understanding of the cellular and molecular bases of longevity and to indicate the most suitable biological models of investigation.

Animals↗
PubMed1986

Function of the spine.

In spite of the considerable effort which has been invested in attempts to understand the mechanism of human spines, substantial controversy remains, particularly in connection with assumptions which have to be made by those engaged in biological modelling. The hypothesis presented here is that the living joint has stress sensors driving a feedback mechanism, an arrangement which could react to imposed loads by modifying muscular action in such a way as to minimize stress at the joints and therefore the risk of injury. A theory of this kind gives an image of the spine not in terms of a spatial picture, as would a CAT scan, but in terms of stresses, forces and moments acting at the intervertebral joints. Calculations show that the erectores spinae alone cannot support more than about 50 kg; there must be some other mechanism to explain man's ability substantially to exceed that load. It is suggested that the interaction between the erectores spinae and the abdominals are of fundamental importance in the function of the spine; how they are co-ordinated during the lifting of weights is examined in detail. The theory resulting from this hypothesis is used to relate spinal injury and an injured subject's posture and behaviour. A mathematical formulation permits an objective evaluation of the spine, and a procedure for determining an automatic diagnosis of lumbar spine disabilities is proposed.

Animals↗
PubMed1984

Plasma L-tryptophan/neutral amino acid ratio and dexamethasone suppression in depression.

We examined the ratio of plasma L-tryptophan (L-TRP) to other neutral amino acids (NAA) in normal controls and depressed patients undergoing a dexamethsone suppression test (DST). The L-TRP/NAA ratio discriminated controls from patients; however, there was no difference in the mean L-TRP/NAA ratio between DST suppressors and nonsuppressors. The cortisol level measured at 1600h postdexamethasone and the L-TRP/NAA ratio were positively correlated. The 1600h postdexamethasone cortisol levels accounted for 24% of the variance of Hamilton Depression Rating Scale ( HDRS ) scores. The inclusion of L-TRP/NAA ratios with 1600h postdexamethasone cortisol levels in a multiple regression equation resulted in an increase in this value and accounted for 65% of the variance in HDRS scores. The finding supports the use of multivariate biological models in depression.

Adult↗
PubMed1993

Electromagnetic fields: a cancer promoter?

This paper discusses some of the current questions observed in updated research analyzing the association of electromagnetic fields (EMF) exposure and cancer. It reveals the predominant efforts toward obtaining more accurate levels of EMF exposure as a crucial key to gain knowledge about that association. A general picture of a molecular biological model of cancer is presented, showing that EMF presents certain compatible characteristics of a cancer promoter. Further, we raise the hypothesis that EMF action is probably linked with other unknown initiator agents, rather than acting alone as presently assumed in epidemiologic studies. Finally this paper reinforces the importance of strong descriptive analysis of potential factors acting together on EMF and cancer association.

Cocarcinogenesis↗
PubMed2006

Failure of calcium microdomain generation and pathological consequences.

Normal physiological regulation depends on Ca(2+) microdomains, because there is a need to spatially separate Ca(2+) regulation of different cellular processes. It is only possible to generate local Ca(2+) signals transiently; so, there is an important functional link between Ca(2+) spiking and microdomains. The pancreatic acinar cell provides a useful cell biological model, because of its clear structural and functional polarization. Although local Ca(2+) spiking in the apical (granular) microdomain regulates fluid and enzyme secretion, prolonged global elevations of the cytosolic Ca(2+) concentration are associated with the human disease acute pancreatitis, in which proteases in the granular region become inappropriately activated and digest the pancreas and its surroundings. A major cause of pancreatitis is alcohol abuse and it has now been established that fatty acid ethyl esters and fatty acids, non-oxidative alcohol metabolites, are principally responsible for causing the acinar cell damage. The fatty acid ethyl esters release Ca(2+) from the endoplasmic reticulum and the fatty acids inhibit markedly mitochondrial ATP generation, which prevents the acinar cell from disposing of the excess Ca(2+) in the cytosol. Because of the abolition of ATP-dependent Ca(2+) pump activity, all intracellular Ca(2+) concentration gradients disappear and the most important part of the normal regulatory machinery is thereby destroyed. The end stage is necrosis.

Adenosine Triphosphate↗