Weighted finite population sampling to maximize entropy

Attention is drawn to a method of sampling a finite populationof N units with unequal probabilities and without replacement.The method was originally proposed by Stern & Cover (1989)as a model for lotteries. The method can be characterized asmaximizing entropy given coverage probabilities _i, or equivalentlyas having the probability of a selected sample proportionalto the product of a set of ‘weights’ w_i. We showthe essential uniqueness of the w_i given the _i. We present twomethods for stepwise selection of sampling units, and correspondingschemes for removal of units that can be used in connectionwith sample rotation. Inclusion probabilities of any order canbe written explicitly in closed form. Second-order inclusionprobabilities _ij satisfy the condition O < _ij < _ij, whichguarantees Yates & Grundy‘s variance estimator tobe unbiased, definable for all samples and always nonnegativefor any sample size.     

Compensatory Roles of Nitrogen Uptake and Photosynthetic N-use Efficiency in Determining Plant Growth Response to Elevated CO2: Evaluation Using a Functional Balance Model

We used a modified functional balance (FB) model to predictgrowth response of Helianthus annuus L. to elevated CO₂. Modelpredictions were evaluated against measurements obtained twiceduring the experiment. There was a good agreement between modelpredictions of relative growth rate (RGR) responses to elevatedCO₂and observations, particularly at the second harvest. Themodel was then used to compare the relative effects of biomassallocation to roots, nitrogen (N) uptake and photosyntheticN-use efficiency (PNUE) in determining plant growth responseto elevated CO₂. The model predicted that a rather substantialincrease in biomass allocation to root growth had little effecton whole plant growth response to elevated CO₂, suggesting thatplasticity in root allocation is relatively unimportant in determininggrowth response. Average N uptake rate at elevated comparedto ambient CO₂was decreased by 21–29%. In contrast, elevatedCO₂increased PNUE by approx. 50% due to a corresponding risein the CO₂-saturation factor for carboxylation at elevated CO₂.The model predicted that the decreased N uptake rate at elevatedCO₂lowered RGR modestly, but this effect was counterbalancedby an increase in PNUE resulting in a positive CO₂effect ongrowth. Increased PNUE may also explain why in many experimentselevated CO₂enhances biomass accumulation despite a significantdrop in tissue nitrogen concentration. The formulation of theFB model as presented here successfully predicted plant growthresponses to elevated CO₂. It also proved effective in resolvingwhich plant properties had the greatest leverage on such responses.Copyright 2000 Annals of Botany Company Elevated CO₂, functional balance model, Helianthus annuus L., N uptake, photosynthetic nitrogen use efficiency, root:shoot ratio     

Intragenic Hill-Robertson interference influences selection intensity on synonymous mutations in Drosophila

Natural selection influences synonymous mutations and synonymouscodon usage in many eukaryotes to improve the efficiency oftranslation in highly expressed genes. Recent studies of genecomposition in eukaryotes have shown that codon usage also variesindependently of expression levels, both among genes and atthe intragenic level. Here, we investigate rates of evolution(Ks) and intensity of selection (_s) on synonymous mutationsin two groups of genes that differ greatly in the length oftheir exons, but with equivalent levels of gene expression andrates of crossing-over in Drosophila melanogaster. We estimate_s using patterns of divergence and polymorphism in 50 Drosophilagenes (100 kb of coding sequence) to take into account possiblevariation in mutation trends across the genome, among genesor among codons. We show that genes with long exons exhibithigher Ks and reduced _s compared to genes with short exons.We also show that Ks and _s vary significantly across long exons,with higher Ks and reduced _s in the central region comparedto flanking regions of the same exons, hence indicating thatthe difference between genes with short and long exons can bemostly attributed to the central region of these long exons.Although amino acid composition can also play a significantrole when estimating Ks and _s, our analyses show that the differencesin Ks and _s between genes with short and long exons and acrosslong exons cannot be explained by differences in protein composition.All these results are consistent with the Interference Selection(IS) model that proposes that the Hill-Robertson (HR) effectcaused by many weakly selected mutations has detectable evolutionaryconsequences at the intragenic level in genomes with recombination.Under the IS model, exon size and exon-intron structure influencethe effectiveness of selection, with long exons showing reducedeffectiveness of selection when compared to small exons andthe central region of long exons showing reduced intensity ofselection compared to flanking coding regions. Finally, ourresults further stress the need to consider selection on synonymousmutations and its variation—among and across genes andexons—in studies of protein evolution.     

Time of Flowering of Pea (Pisum sativum L.) as a Function of Leaf Appearance Rate and Node of First Flower

In order to assess the influence of environmental conditionson time of flowering of pea (Pisum sativum L.), a serial sowingtrial was conducted over 2 years at Dijon, France, on two wintercultivars Frisson and Frilene. Time of flowering was analysedaccording to two variables: the leaf appearance rate R_L andthe node of first flower N_I. R_L was linearly related to temperature (r² = 0·94). Thebase temperature was 2°C for both varieties. Growth rateaccounted for the residual variability of R_L . Photoperiod andtemperature acted on N_I in an additive way. Frilene, the latergenotype, was more responsive than Frisson. A model for predicting time of flowering based upon these resultsis proposed. Deviations from this model were related to N nutritionin interaction with the plant water relations. Steps for improvingthe model are then discussed.Copyright 1993, 1999 Academic Press Pisum sativum L., pea, flowering, temperature, photoperiod, phyllochron, model     

Modelling steady-state growth and photosynthesis rates of Oscillatoria rubescens continuous cultures in relation to temperature and irradiance

The lacustrine blue-green alga (= Cyanobacterium) Oscillatoriarubescens D.C. was cultured in chemostats with temperature andlight intensity as the only limiting factors. The experimentswere carried out under combinations of three temperatures 10,20 and 30°C and three irradiances 6, 18 and 30 µEm^–2 s^–1. Dilution rate, photosynthesis rate anda large number of abiotic and cellular factors were regularlymeasured to determine steady-state periods and the level ofthe associated variables. Various mathematical models were fittedwith series of data by a non-linear regression method derivedfrom Marquardt's method. Four models for calculation of specificgrowth rate and photosynthesis rate are presented. The lastone computes growth rate from calculated photosynthesis: µ= µ_max p_maxI/[K_pK_i + I(K_p + P_max)], with P_max =100 + 257Tand K₁ = 300/chl a. Values of adjusted parameters are discussed.One conclusion confirms that values of maximal growth ratesand half-saturation constants frequently considered in the literatureas absolute species characteristics should always be consideredas relative to associated prevalent growth conditions.     

Cuticular water permeability and its physiological significance

Cuticles act as solution-diffusion membranes for water transport.Diffusion in pores does not contribute to cuticular transpiration.An extensive literature survey of cuticular permeances (P) andminimum leaf conductances (g_min) to water is presented. Thetwo variables cannot be distinguished with most experimentaltechniques. Results from different experiments are in good agreementwith each other for some species, for example, Fagus sytvaticaL., but not for others, such as Picea abies (L.) Karst. In adata set of 313 values of P or g_min from 200 species, distributionsof results obtained with different techniques were found todiffer significantly. Likely reasons include water loss fromincompletely closed or incompletely sealed stomata, and thedependence of P on moisture content of the cuticle and on storagetime of isolated cuticles. Contrasting evidence for an interactionbetween cuticular transpiration and stomatal sensitivity toair humidity is presented. The occurrence of unusually highg_min in trees growing at the alpine treeline and its physiologicalsignificance are discussed. It is shown that g_min is of littlevalue as a predictor for drought resistance of crops, with thepossible exception of Sorghum bicolor L. Moench. Possible wateruptake from fog or dew across cuticles is considered briefly. Key words: Epidermal conductance, VPD-response, water absorption, waxes, winter desiccation     

Positive Association Among Three Binary Variables and Cross-Product Ratios

We show that, when the three-way association level among thethree binary variables, X, U₁ and U₂ is fixed, D_P = pr(X = 1¦U₁= 1) – pr(X = 1¦U₁ = 0) increases as the cross-productratio of U₁ and U₂ increases under the assumption that X ispositively associated with U₁ and U₂. We then discuss some implicationsof this property.     

Effects of Seasonal Variation in Radiation and Temperature on Net Assimilation and Growth Rates in an Arid Climate

The net assimilation rate (E_A), relative growth-rate (R_w), andleaf-area ratio (F_A) were measured for rape (Brassica napus),sunflower (Hetianthus annuus), and maize (Zea mays) at varioustimes of year in an arid climate, using young plants grown widelyspaced on nutrient culture. Multiple regression analysis accountedfor 90–95 per cent of the variation in E_A and R_W in termsof two climatic variables: mean temperature and radiation receipt. E_A rose linearly with radiation in all three species; increasein E_A with temperature was greatest in maize and least (notsignificant) in rape. R_Wrose with radiation and temperature,the latter being the more important variable especially in coolweather; a temperature optimum was shown at 24° C in rape.F_A rose with increase in temperature or decrease in radiation;its variation was due to change in leaf area/leaf weight ratherthan in leaf weight/plant weight. Multiple regression analyses can lead to faulty interpretationif the independent variables are correlated (as are climaticvariables in nature), but conclusions can be checked by controlled-environmentstudies in which climatic factors are not correlated. The presentconclusions are supported by such studies. The regression equations, coupled with average weather records,indicate seasonal cycles of growth parameters. E_A is maximalnear midsummer and minimal near midwinter, following the radiationcycle. Maxima and minima in R_W are about a month later, becauseR_W is affected by the temperature cycle and this lags behindthe radiation cycle. F_A is maximal in autumn and minimal inspring. E_A is highest where radiation receipts near 750 cal cm^–2day^–1 coincide with high temperatures. This combinationoccurs only in clear midsummer weather at low latitudes, andis maintained over long periods only in arid regions. The fact that E_A rose linearly with radiation suggests thatleaf water deficits arising under high radiation had littleeffect on E_A and that saturating levels of light were very high.     

A computational analysis of central CO2 chemosensitivity in Helix aspersa

We created a single-compartment computer model of a CO₂ chemosensory neuron using differential equations adapted from the Hodgkin-Huxley model and measurements of currents in CO₂ chemosensory neurons from Helix aspersa. We incorporated into the model two inward currents, a sodium current and a calcium current, three outward potassium currents, an A-type current (I_KA), a delayed rectifier current (I_KDR), a calcium-activated potassium current (I_KCa), and a proton conductance found in invertebrate cells. All of the potassium channels were inhibited by reduced pH. We also included the pH regulatory process to mimic the effect of the sodium-hydrogen exchanger (NHE) described in these cells during hypercapnic stimulation. The model displayed chemosensory behavior (increased spike frequency during acid stimulation), and all three potassium channels participated in the chemosensory response and shaped the temporal characteristics of the response to acid stimulation. pH-dependent inhibition of I_KA initiated the response to CO₂, but hypercapnic inhibition of I_KDR and I_KCa affected the duration of the excitatory response to hypercapnia. The presence or absence of NHE activity altered the chemosensory response over time and demonstrated the inadvisability of effective intracellular pH (pH_i) regulation in cells designed to act as chemostats for acid-base regulation. The results of the model indicate that multiple channels contribute to CO₂ chemosensitivity, but the primary sensor is probably I_KA. pH_i may be a sufficient chemosensory stimulus, but it may not be a necessary stimulus: either pH_i or extracellular pH can be an effective stimuli if chemosensory neurons express appropriate pH-sensitive channels. The lack of pH_i regulation is a key feature determining the neuronal activity of chemosensory cells over time, and the balanced lack of pH_i regulation during hypercapnia probably depends on intracellular activation of pH_i regulation but extracellular inhibition of pH_i regulation. These general principles are applicable to all CO₂ chemosensory cells in vertebrate and invertebrate neurons. hypercapnia; potassium channels; computer modeling; central chemoreceptors     

Energy-Level Model for Isothermal Seed Germination

We have been successful in building an energy-level model thatdescribes seed germination. We used the autocatalytic reactionrate equation to fit the germination rate for seed germination.The two parameters [A]₀ and [F]₀ were found by fitting the integratedgermination rate equation to the data. The values of [A]₀ and[F]₀ obey the Arrhenius equation and give activation energiesfor the second and third stage of the four-compartmental modelof seed germination. The thermodynamics of isothermal seed germinationis proposed and the enthalpy, entropy, and free energy are calculatedfor the transition from state A to state F. The time delay isa function of temperature and it leads to a rate constant thatcan be used to get the activation energy for the total germinationprocess. We believe the model is universal. It fits alfalfa(Medicago sativa), turnip (Brassica rapa), and lettuce (Lactucasativa) seeds. Key words: Seed germination, thermodynamics, kinetics, Arrhenius, energy-level model     

甜菜夜蛾对虫酰肼的抗性选育、风险评估及交互抗性

虫酰肼是目前防治甜菜夜蛾Spodoptera exigua（Hübner）的一种主要杀虫剂,为评估其抗性风险,在室内进行了抗性筛选和交互抗性的研究。采用饲料感染法,在甜菜夜蛾饲养75代期间用虫酰肼筛选62代,与起始种群相比抗性上升39.2倍,与室内敏感品系相比抗性上升141.3倍。在筛选的早、中、后期,现实遗传力h²分别为0.1075（F₀～F₂₅）、0.2780（F₂₆～F₅₀）和0.0538（F₅₁～F₇₅）,整个筛选62代现实遗传力为0.1556。抗性种群筛选43次（F55）后停止用药筛选,饲养21代后,与敏感品系相比,抗性水平由63.5倍下降到21倍,抗性下降3倍。说明甜菜夜蛾具有对虫酰肼产生抗性的风险,且抗性衰退缓慢,短期内很难恢复到敏感水平。交互抗性测定结果表明,上述室内选育的抗性品系对甲氧虫酰肼具有71.4倍的高水平交互抗性,对阿维菌素具有13.1倍的中等水平交互抗性,对甲维盐、茚虫威和呋喃虫酰肼分别具有7.0、8.4和4.7倍的低水平交互抗性,但对溴虫腈交互抗性不明显（1.9倍）。结果提示： 间断交替使用虫酰肼可以延缓抗性的发展,但除溴虫腈外,虫酰肼和其他几种新型杀虫剂之间的轮用可能不是甜菜夜蛾抗性治理的有效策略。     

Limitations on the Analysis of Acetylene Reduction by Soybean at Low Levels of Acetylene

The analysis of acetylene reduction at low concentrations ofacetylene involves a number of assumptions and both technicaland kinetic complexities. The major difficulty in convertingacetylene reduction rates to apparent N₂ reduction rates isdetermining the K_m for acetylene in the presence of N₂. Thissubstrate competition is dominant over diffusion limitationeffects, but both introduce equivalent deviations in the observedK_m. Because N₂ is a non-linear partial competitive inhibitorof acetylene reduction, correction for its presence is difficult.Two further complications are introduced by the non-linear responseof nitrogenase to acetylene concentration even in the absenceof N₂, and changes in the apparent K_m of acetylene and K₁ ofN₂ as a function of other variables in the enzyme assay. Itis proposed that transient analysis may be used for measurementof diffusion coefficients and calculations of possible diffusionlimitations. It is demonstrated that one proposed model forestimating diffusion limitation (Denison et al., 1983, PlantPhysiology 73, 648–51) confounds substrate competitionwith diffusion limitation. Acetylene reduction, nitrogen fixation, diffusion limitation     

Dynamics of calcium regulation of chloride currents in Xenopus oocytes

Ca-activated Cl currents are widely expressed in many cell typesand play diverse and important physiological roles. TheXenopus oocyte is a good model systemfor studying the regulation of these currents. We previously showedthat inositol 1,4,5-trisphosphate (IP₃) injection intoXenopus oocytes rapidly elicits anoninactivating outward Cl current(I_Cl1-S)followed several minutes later by the development of slow inward(I_Cl2) andtransient outward(I_Cl1-T) Clcurrents. In this paper, we investigate whether these three currentsare mediated by the same or different Cl channels. Outward Cl currentswere more sensitive to Ca than inward Cl currents, as shown byinjection of different amounts of Ca or by Ca influx through aheterologously expressed ligand-gated Ca channel, the ionotropicglutamate receptor iGluR3. These data could be explained by twochannels with different Ca affinities or one channel with a higher Caaffinity at depolarized potentials. To distinguish between thesepossibilities, we determined the anion selectivity of the threecurrents. The anion selectivity sequences for the three currents werethe same (I > Br > Cl), butI_Cl1-Shad an I-to-Cl permeability ratio more than twofold smaller than the other two currents. The different anion selectivities and instantaneous current-voltage relationships were consistent with at least two different channels mediating these currents. However, afterconsideration of possible errors, the hypothesis that a single type ofCl channel underlies the complex waveforms of the three differentmacroscopic Ca-activated Cl currents inXenopus oocytes remains a viable alternative.

     

Modeling transmural heterogeneity of K(ATP) current in rabbit ventricular myocytes

To investigate the mechanisms regulating excitation-metabolic coupling in rabbit epicardial, midmyocardial, and endocardial ventricular myocytes we extended the LabHEART model (Puglisi JL and Bers DM. Am J Physiol Cell Physiol 281: C2049–C2060, 2001). We incorporated equations for Ca²⁺ and Mg²⁺ buffering by ATP and ADP, equations for nucleotide regulation of ATP-sensitive K⁺ channel and L-type Ca²⁺ channel, Na⁺-K⁺-ATPase, and sarcolemmal and sarcoplasmic Ca²⁺-ATPases, and equations describing the basic pathways (creatine and adenylate kinase reactions) known to communicate the flux changes generated by intracellular ATPases. Under normal conditions and during 20 min of ischemia, the three regions were characterized by different I_Na, I_to, I_Kr, I_Ks, and I_Kp channel properties. The results indicate that the ATP-sensitive K⁺ channel is activated by the smallest reduction in ATP in epicardial cells and largest in endocardial cells when cytosolic ADP, AMP, PCr, Cr, P_i, total Mg²⁺, Na⁺, K⁺, Ca²⁺, and pH diastolic levels are normal. The model predicts that only K_ATP ionophore (Kir6.2 subunit) and not the regulatory subunit (SUR2A) might differ from endocardium to epicardium. The analysis suggests that during ischemia, the inhomogeneous accumulation of the metabolites in the tissue sublayers may alter in a very irregular manner the K_ATP channel opening through metabolic interactions with the endogenous PI cascade (PIP₂, PIP) that in turn may cause differential action potential shortening among the ventricular myocyte subtypes. The model predictions are in qualitative agreement with experimental data measured under normal and ischemic conditions in rabbit ventricular myocytes. ATP-sensitive K⁺ channel; creatine and adenylate kinase reactions; phosphatidylinositol phosphates; heart; mathematical model     

Ca transients from Ca channel activity in rat cardiac myocytes reveal dynamics of dyad cleft and troponin C Ca binding

The properties of the dyad cleft can in principle significantly impact excitation-contraction coupling, but these properties are not easily amenable to experimental investigation. We simultaneously measured the time course of the rise in integrated Ca current (I_Ca) and the rise in concentration of fura 2 with Ca bound ([Ca-fura 2]) with high time resolution in rat myocytes for conditions under which Ca entry is only via L-type Ca channels and sarcoplasmic reticulum (SR) Ca release is blocked, and compared these measurements with predictions from a finite-element model of cellular Ca diffusion. We found that 1) the time course of the rise of [Ca-fura 2] follows the time course of integrated I_Ca plus a brief delay (1.36 ± 0.43 ms, n = 6 cells); 2) from the model, high-affinity Ca binding sites in the dyad cleft at the level previously envisioned would result in a much greater delay (=" BORDER="0">3 ms) and are therefore unlikely to be present at that level; 3) including ATP in the model promoted Ca efflux from the dyad cleft by a factor of 1.57 when low-affinity cleft Ca binding sites were present; 4) the data could only be fit to the model if myofibrillar troponin C (TnC) Ca binding were low affinity (4.56 µM), like that of soluble troponin C, instead of the high-affinity value usually used (0.38 µM). In a "good model," the rate constants for Ca binding and dissociation were 0.375 times the values for soluble TnC; and 5) consequently, intracellular Ca buffering at the rise of the Ca transient is inferred to be low. excitation-contraction coupling; adenosine triphosphate; fura 2; modeling; fuzzy space     

Heritability of three condition surrogates in the yellow dung fly

Condition capture has been proposed as a general mechanism maintainingadditive genetic variation, V_a, in sexually selected traitsunder directional selection. It relies on two main assumptions:condition-dependent trait expression and V_a in condition. Althoughthere is evidence for the former, direct evidence that conditionis heritable is scarce, although this is a requirement of mostmodels of handicap sexual selection. We used a parent–offspring,full-sib, two-container laboratory breeding design in the yellowdung fly Scathophaga stercoraria to demonstrate the broad- andnarrow-sense heritability of three surrogates of condition commonlyused in sexual selection studies: lipid and glycogen reserves(i.e., physiological condition), body size, and fluctuatingasymmetry. All three measures are nutrition dependent and havebeen linked to sexual selection in free-living yellow dung flies.While lipid reserves and body size were heritable, asymmetryand glycogen reserves were not. Moreover, the evolvability ofphysiological condition was higher than that of the other twotraits. Of the three surrogates, physiological condition ismost akin to the original definition, but all have their limitations.We conclude that condition is a useful heuristic concept inevolutionary ecology, but its practical value may be limitedby the fact that it cannot be measured directly.     

Common canonical variates

Canonical correlation analysis measures the linear relationshipbetween two random vectors X₁ and X₂ as the maximum correlationbetween linear combinations of X₁ and linear combinations ofX₂. Several generalisations of canonical correlation analysisto k2 random vectors X₁ ..., X_k have been proposed in the literature(Kettenring, 1971, 1985), based on the principle of maximisingsome generalised measure of correlation. In this paper we proposean alternative generalisation, called common canonical variates,based on the assumption that the canonical variates have thesame coefficients in all k sets of variables. This generalisationis applicable in situations where all X_i have the same dimension.We present normal theory maximum likelihood estimation of commoncanonical variates, and illustrate their use on a morphometricdata set.     

The Effect of Temperature on Leaf Appearance in Rice

Temperature is the principal environmental determinant of cropleaf appearance. The objective of this study is to analyse whetherthere are different effects of day temperature (T_D) and nighttemperature (T_N) on main-stem leaf appearance in rice (OryzasativaL.). Plants of 12 rice cultivars were grown at five constant temperatures(22, 24, 26, 28 and 32 °C) and four diurnally fluctuatingtemperatures (T_D/T_N: 26 /22, 30 /22, 22 /26 and 22 /30 °C)with a constant photoperiod of 12hd^-1. The leaf appearance onthe main stem was measured. A constant change in leaf appearance rate was observed duringontogeny. The relation between the number of emerged leavesand days from seedling emergence was described by a power-lawequation with only one cultivar-specific parameter. Values forthis parameter were estimated for the five constant temperaturetreatments, and the relation between this parameter and temperaturewas quantified by a nonlinear model. Leaf appearance for thefour fluctuating temperature treatments could be accuratelypredicted on the basis of these relations in each cultivar.This indicated that there were no specific effects ofT_DandT_Nonleaf appearance in rice, in contrast with phenological developmentto flowering. The optimum temperature for leaf development wasfound to be substantially higher than for development to flowering. The final main-stem leaf number differed with diurnal temperatureconditions. When a diurnal temperature delayed flowering, itincreased the leaf number as well. This might explain whyT_DandT_Nhada different effect on development to flowering but not on leafdevelopment. Oryza sativa; rice; leaf appearance; leaf number; day and night temperature     

Relationship between T-wave amplitude and oxygen pulse in guinea pigs in hyperbaric helium and hydrogen

Diving isknown to induce a change in the amplitude of the T wave(A_Tw) ofelectrocardiograms, but it is unknown whether this is linked to achange in cardiovascular performance. We analyzed A_Tw in guinea pigs at 10-60atm and 25-36°C, breathing 2%O₂ in either helium (heliox;n = 10) or hydrogen (hydrox;n = 9) for 1 h at each pressure. Coretemperature and electrocardiograms were detected by using implantedradiotelemeters. O₂ consumption rate was measured by using gas chromatography. In a previous study (S. R. Kayar and E. C. Parker. J. Appl.Physiol. 82: 988-997, 1997), we analyzed theO₂ pulse, i.e., theO₂ consumption rate per heartbeat, in the same animals. By multivariate regression analysis, weidentified variables that were significant toO₂ pulse: body surface area,chamber temperature, core temperature, and pressure. In this study,inclusion of A_Tw made asignificantly better model with fewer variables. After normalizing forchamber temperature and pressure, theO₂ pulse increased with increasing A_Tw in heliox(P = 0.001) but with decreasingA_Tw in hydrox(P < 0.001). ThusA_Tw is associated with thedifferences in O₂ pulse foranimals breathing heliox vs. hydrox.

     

LabHEART: an interactive computer model of rabbit ventricular myocyte ion channels and Ca transport

An interactive computer program,LabHEART, was developed to simulate the action potential (AP), ioniccurrents, and Ca handling mechanisms in a rabbit ventricular myocyte.User-oriented, its design allows switching between voltage and currentclamp and easy on-line manipulation of key parameters to change theoriginal formulation. The model reproduces normal rabbit ventricularmyocyte currents, Ca transients, and APs. We also changed parameters to simulate data from heart failure (HF) myocytes, including reduced transient outward (I_to) and inward rectifying Kcurrents (I_K1), enhanced Na/Ca exchangeexpression, and reduced sarcoplasmic reticulum Ca-ATPase function, butunaltered Ca current density. These changes caused reduced Ca transientamplitude and increased AP duration (especially at lower frequency) asobserved experimentally. The model shows that the increased Na/Caexchange current (I_NaCa) in HF lowers theintracellular [Ca] threshold for a triggered AP from 800 to 540 nM. Similarly, the decrease in I_K1reduces the threshold to 600 nM. Changes in I_tohave no effect. Combining enhanced Na/Ca exchange with reducedI_K1 (as in HF) lowers the threshold to triggeran AP to 380 nM. These changes reproduce experimental results inHF, where the contributions of different factors are notreadily distinguishable. We conclude that the triggered APs thatcontribute to nonreentrant ventricular tachycardia in HF are dueapproximately equally (and nearly additively) to alterations inI_NaCa and I_K1. A freecopy of this software can be obtained athttp://www.meddean.luc.edu/lumen/DeptWebs/physio/bers.html.