Homozygosity in a population of variable size and mutation rate

A formula is obtained for the probability that two genes at a single locus, sampled at random from a population at time t, are of particular types. The model assumed is a diffusion approximation to a neutral Wright-Fisher model in which mutation is not necessarily symmetric and the population size is a function of time. It is shown that for symmetric mutation in a population undergoing a step-function type bottleneck, homozygosity increases with decreasing population size. A formula is given for the distribution of the number of segregating sites occurring in two randomly sampled sequences of completely linked sites, with general mutation at a site and identical mutation structure between sites.We give similar results for a population of fixed size but for which the mutation rate is a function of time, and not necessarily symmetric. We confirm the intuitively clear effect that increasing the mutation rate decreases homozygosity.     

A general framework for understanding the effects of variability and interruptions on foraging behaviour

A general framework for analysing the effects of variability and the effects of interruptions on foraging is presented. The animal is characterised by its level of energetic reserves, x. We consider behaviour over a period of time [0,T]. A terminal reward function R(x) determines the expected future reproductive success of an animal with reserves x at time T. For any state x at a time in the period, we give the animal a choice between various options and then constrain it to follow a background strategy. The best option is the one that maximizes expected future reproductive success. Using this framework, we show that sensitivity to variability in amount of energy gained is logically distinct from sensitivity to variability in the time at which food is obtained. We also show that incorporating interruptions results in both a preference for variability in time and a preference for a reward followed by a delay as opposed to the same delay before the reward.     

Structure of the Tet repressor and Tet repressor-operator complexes in solution from electrooptical measurements and hydrodynamic simulations

The Tet repressor protein and tet operator DNA fragments and their complexes have been analyzed by electrooptical procedures. The protein shows a positive linear dichroism at 280 nm, a negative linear dichroism at 248 nm, and a strong permanent dipole moment of 3.5 X 10(-27) C m, which is independent of the salt concentration within experimental accuracy. Its rotation time constant of 40 ns indicates an elongated structure, which is consistent with a prolate ellipsoid of 100 A for the long axis and 40 A for the short axis. The time constant can also be fitted by a cylinder of length 78 A and diameter 37 A, which is consistent with nuclease protection data reported on repressor-operator complexes, if the cylinder axis is aligned parallel to the DNA axis. Addition of tetracycline induces changes of the limit dichroism but very little change of the rotation time constant. The rotation time constants observed for the operator DNA fragments show some deviations from the values expected from their contour length; however, these deviations remain relatively small. Formation of repressor-operator complexes leads to some increase of the DNA rotation time constants. Simulations by bead models demonstrate that these time constants can be explained without any major change of the hydrodynamic dimension of the components. The data for the complexes are fitted by bead models with smooth bending of the DNA corresponding to a radius of curvature of 500 A, but at the given accuracy, we cannot rule out that the DNA in the complex remains straight or is bent to a smaller radius of approximately 400 A. Thus, binding of the Tet repressor, which is a helix-turn-helix protein as judged from its sequence, to its operator seems to induce minor bending but does not induce strong bending of the DNA double helix.     

Stochastic growth and extinction in a spatial geometric Brownian population model with migration and correlated noise

A continuous spatial model for populations that are not density-regulated is analyzed. The model is a generalization of the geometric Brownian motion often used to describe populations at a single location. The locations are linked by migration and spatial correlation in the noise. At any point of time, the population size at a given location is log normally distributed so the log population size constitutes a Gaussian field. The model is homogeneous in space but not in time. In particular, we analyze the case when the stochastic growth rate is negative and the total population approaches extinction. The properties of the extinction process is studied by considering local quasi-extinctions. A major conclusion is that migration tends to increase the time to extinction provided that there is no cost of migration. However, as the area occupied by the species starts to decrease, the decrease is faster for populations with larger migration.     

Variation at two flowering time genes within and among populations of Arabidopsis thaliana: comparison with markers and traits

Flowering Locus C (FLC) and Frigida are two interacting genes controlling flowering time variation in Arabidopsis thaliana. Variation at these genes was surveyed in 12 A. thaliana populations sampled in France. These populations were also screened for variation at molecular markers [12 microsatellites and 19 cleaved amplified polymorphic sequence (CAPS) markers] and at seven quantitative traits measured with and without vernalization. Seven populations were highly polymorphic at markers (H(S) = 0.57 at microsatellites, 0.24 at CAPS) and showed heritable variation for bolting time and some other traits. Five populations were genetically fixed or nearly fixed. Q(ST) for bolting time without vernalization was significantly higher than F(ST), suggesting local divergent selection. One of the two haplotype groups at FLC (FLC(A)) was very predominant (frequency of 99%). The first exon of Frigida showed elevated nonsynonymous variation, and nine loss-of-function mutations were found throughout the gene. The association between loss-of-function and earlier bolting was confirmed. Overall, 18 Frigida haplotypes were detected. The pattern of variation at Frigida was largely similar to that found at markers and traits, with the same populations being fixed or highly diverse. Metapopulation dynamics is thus probably the main factor shaping genetic variation in A. thaliana. However, F(ST) for functional (FRI) vs. nonfunctional (FRI(Delta)) haplotypes was significantly higher than F(ST) at markers. This suggested that loss-of-function at Frigida is under local selection for flowering time.     

Time perception,emotions and mood disorders

In this review, we describe recent internal clock models accounting for time perception and look at how they try to explain the time distortions produced by emotion. We then discuss the results of studies of patients suffering from affective disorders (depression) who experience the feeling of time slowing down. A distinction is thus made between time perception and explicit awareness of the passage of time. We conclude that the feeling that time is passing slowly is not systematically associated with a disruption in the basic mechanisms underlying time perception.     

Mathematical description of the seed germination dependency on time and temperature

Abstract. A mathematical model which describes the germination percentage dependency on time and temperature of a seed population was derived from the experimental results with a seed population of Amaranthus patulus Bertol. under sub-optimal temperature conditions (Washitani & Takenaka, 1984). The equation of the model which is a modified thermal time model is where G is germination percentage at a certain time after the start of imbibition ( t ) at a certain temperature ( T ), μ _{T 1} and σ _{T 1} are the mean and standard deviation of lower limit temperature among the seeds belonging to the seed population, and Tb, m , and A are the parameters characterizing the linear relationship between the rate and temperature, namely, Tb is the base temperature, m , the median of the required thermal time and A , a parameter determining the pattern of the variation of the required thermal time within seed population, respectively. The equation yields time courses for germination which are very similar to those observed by experiment.     

下腹部手术麻醉中不同靶浓度瑞芬太尼与异丙酚的作用研究

目的研究下腹部手术麻醉患者应用不同靶浓度瑞芬太尼和异丙酚的作用效果。方法将我院收治的下腹部手术麻醉患者为研究对象,并按随机分组法分为3组,均固定瑞芬太尼靶浓度,A组为6ng/ml,B组为8ng/ml,C组为10ng/ml,同时改变异丙酚靶浓度,范围为2~4μg/ml,观察比较各组的麻醉效果。结果 T1时刻A组的收缩压(SBR)高于B组,心率(HR)高于C组,差异有统计学意义(P0.05);而T2、T3时刻比较,A组的SBR以及HR均较B、C组高(P0.05)。随时间推移,去甲肾上腺素(NE)各时点比较,T1时刻A组的NE高于C组,而血清皮质醇(COR)低于B、C组;T2、T3时刻A组的NE均显著高于B、C组,但3组COR变化无显著差异性(P0.05)。C组自主呼吸恢复时间、拔除气管导管时间、指令反应时间和离室时间均较长,而其睁眼时间较短(P0.05)。结论将瑞芬太尼靶浓度调节为8ng/ml,可取得较为明显的麻醉镇痛效果。     

Water proton magnetic resonance studies of normal and sickle erythrocytes. Temperature and volume dependence.

The temperature and cell volume dependence of the NMR water proton line-width, spin-lattice, and spin-spin relaxation times have been studied for normal and sickle erythrocytes as well as hemoglobin A and hemoglobin S solutions. Upon deoxygenation, the spin-spin relaxation time (T2) decreases by a factor of 2 for sickle cells and hemoglobin S solutions but remains relatively constant for normal cells and hemoglobin A solutions. The spin-lattice relaxation time (T1) shows no significant change upon deoxygenation for normal or sickle packed red cells. Studies of the change in the NMR linewidth, T1 and T2 as the cell hydration is changed indicate that these parameters are affected only slightly by a 10-20% cell dehydration. This result suggests that the reported 10% cell dehydration observed with sickling is not important in the altered NMR properties. Low temperature studies of the linewidth and T1 for oxy and deoxy hemoglobin A and hemoglobin S solutions suggest that the "bound" water possesses similar properties for all four species. The low temperature linewidth ranges from about 250 Hz at -15 degrees C to 500 Hz at -36 degrees C and analysis of the NMR curves yield hydration values near 0.4 g water/g hemoglobin for all four species. The low temperature T1 data go through a minimum at -35 degrees C for measurements at 44.4 MHz and -50 degrees C for measurements at 17.1 MHz and are similar for oxy and deoxy hemoglobin A and hemoglobin S. These similarities in the low temperature NMR data for oxy and deoxy hemoglobin A and hemoglobin S suggest a hydrophobically driven sickling mechanism. The room temperature and low temperature relaxation time data for normal and sickle cells are interpreted in terms of a three-state model for intracellular water. In the context of this model the relaxation time data imply that type III, or irrotationally bound water, is altered during the sickling process.     

Satiation and the functional response: a test of a new model

Abstract. 1. A model of the functional response to prey density is derived to include the reduction in time available for search, T_s , resulting from predator satiation.
2. For larger prey items predator satiation occurs at each prey capture and T_s is reduced by the attack time and digestive pause of a series of attack cycles. For small prey items predator foraging is continuous at low densities with T_s reduced solely by attack time. At higher densities predator satiation occurs after the capture of several small prey items and T_s is reduced by the attack time and digestive pause of a series of foraging cycles.
3. A comparison of the predicted asymptotic level of prey capture using experimentally estimated parameter values, with the maximum consumption of aphids by larval and adult coccinellids provides a test of the satiation model.
4. The limitation of prey capture by predator satiation is discussed with reference to handling time and the success of coccinellids in biological control.     

Population dynamics with age- and time-dependent birth and death rates

A continous, deterministic mathematical model is used to predict population distributions by age at any time, given the initial distribution and the variation of birth and death rates with age and time. Solutions are obtained on a computer using a semi-discretization algorithm in which time derivatives in the partial differential equations are replaced by finite-difference expressions. The resulting sets of ordinary differential equations are solved by a predictor-corrector method. Graphical results are shown for some examples.     

A statistical procedure useful in evaluating time of onset and termination of response in clinical trials.

A statistical model jointly characterizing the onset and termination of treatment response of a subject over a fixed observed time period is presented. The model requires that the observations for each subject are made at a set of pre-selected time points during the observed time period. A useful index characterizing the probability of being in response is developed along with maximum likelihood estimates and variances. A likelihood ratio test is developed to simultaneously compare two treatment groups with respect to this index for all times. The proposed procedure is applied to a set of data from a clinical trial of two bronchodilator drugs from which our procedure is motivated.     

Improving protein crystal quality by decoupling nucleation and growth in vapor diffusion

A simple method for growing protein crystals in the metastable zone using the vapor diffusion technique is described. The coverslips holding the hanging drops are transferred, after being incubated for some time at conditions normally giving many small crystals, over reservoirs at concentrations that normally yield clear drops. Fewer, much larger and better diffracting crystals are obtained, compared with conventional crystallization at similar conditions. To our knowledge, this is the first report of a significant crystal improvement due to "backing off" from nucleation conditions, using the hanging drop method. A correlation of the transfer time with published results for vapor diffusion equilibration of poly(ethylene glycol) solutions is also presented.     

小剂量快速注射丙泊酚在胃镜检查中的安全有效性分析

目的：观察小剂量快速注射丙泊酚在无痛胃镜检查中的安全性及有效性,观察该方法对患者识记能力的影响。方法：选择60例行无痛胃镜检查的患者,随机分成A组和B组。所有患者均给予1μg／kg芬太尼。给予芬太尼后1分钟后,A组患者按照5mg／sec的速度给予2mg／kg丙泊酚;B组患者按照20mg／sec的速度给予1mg／kg丙泊酚。患者睫毛反射消失后进行胃镜检查。记录患者基础时及麻醉过程中不同时点的收缩压、舒张压、心率以及脉搏血氧饱和度,记录患者失去意识时间、胃镜检查时间、患者苏醒时间,记录检查过程中有无呛咳、体动,记录患者有无术中知晓,记录患者检查后一周内的有无识记能力的减退。结果：两组患者基本情况无统计学差异;60例患者无一例出现术中知晓;两组患者在麻醉过程中不同时点的循环情况及脉搏血氧饱和度之间没有统计学差异;检查过程中呛咳、体动的发生率组间比较无统计学差异;失去意识时间和苏醒时间组间比较P≤0．05,具有统计学差异;检查后一周内,识记能力减退发生率组间比较具有统计学差异。结论：快速注射小剂量丙泊酚可以保证患者安全、满足无痛胃镜检查的需要,同时可以降低丙泊酚的用量,减少药物蓄积,减少丙泊酚所致的识记功能减退。     

On density and extinction in continuous population models

Survival analyses, investigations of extinction and persistence, are executed for populations represented by a nonautonomous differential equation model. The population is assumed governed by density dependent and time varying density independent demographic parameters. While traditional approaches to extinction postulate extinction on an infinite time horizon and at zero abundance level, survival analysis is developed not only for this traditional setting but also on a finite time horizon and at a nonzero threshold level. A main conclusion is that extinction of a temporally stressed population is determined by a totality of density independent and density dependent factors.     

Solution structure of human GABA(A) receptor-associated protein GABARAP: implications for biolgoical funcrion and its regulation

Control of neurotransmitter receptor expression and delivery to the postsynaptic membrane is of critical importance for neural signal transduction at synapses. The gamma-aminobutyric acid, type A (GABA(A)) receptor-associated protein GABARAP was reported to have an important role for movement and sorting of GABA(A) receptor molecules to the postsynaptic membrane. GABARAP not only binds to GABA(A) receptor gamma2-subunit but also to tubulin, gephyrin, and ULK1. We present for the first time the high resolution structure of human GABARAP determined by nuclear magnetic resonance in aqueous solution. One part of the molecule, despite being well ordered and rigid on a MHz time scale, exists in at least two different conformations that interchange with each other on a time scale slower than 25 Hz. An important feature of the solution structure is the observation that amino- and carboxyl-terminal ends of the protein directly interact with each other, which is not seen in recently reported crystal structures. The possible biological relevance of these observations for the regulation of GABARAP interactions and functions is discussed.     

Adult feeding time, lipid accumulation, and overwintering in Aglais urticae and Inachis io (Lepidoptera: Nymphalidae)

The influence of restricted feeding time on the subsequent survival of adult Aglais urticae and Inachis io during diapause was tested in the laboratory. Abdominal lipid weight increased in the first 7 days of feeding by A. urticae and up to day 15 in I. io. Lipid as a proportion of dry weight also increased during this time. Individuals of both species feeding for 0–3 days began overwintering at significantly lower weights, and percentage weight loss during overwintering was more rapid than for those feeding for longer periods. Differences in fresh weights at the beginning of the overwintering period are reflected by differences in overwintering survival. In A. urticae , all 0–3 day feeders died in less than 150 days, in contrast, over 75% of 7–30 day feeders survived this period. In I. io , all 0–1 day feeders died within 160 days, less than 50% of 3 day feeders survived, whilst over 90% of7–15 day feeders were alive after this time. In I. io individuals feeding for one day, fresh weight is correlated with survival time suggesting that a larger body size may enhance survival time if feeding time is restricted.     

Studies on the time course and rate-limiting steps in the activation of adenylate cyclase in rat liver by cholera toxin.

Cholera toxin stimulates adenylate cyclase in rat liver after intravenous injection. The stimulation follows a short latent period of 10min, and maximum stimulation was attained at 120min. Half-maximal stimulation was achieved at 35min. In contrast with this lengthy time course in the intact cell, adenylate cyclase in broken-cell preparations of rat liver in vitro were maximally stimulated by cholera toxin (in the presence of NAD+) in 20min with half-maximal stimulation in 8min. Binding of cholera toxin to cell membranes by the B subunits is followed by translocation of the A subunit into the cell or cell membrane, and separation of the A1 polypeptide chain from the A2 chain by disulphide-bond reduction, and finally activation of adenylate cyclase by the A1 chain and NAD+. As the binding of cholera toxin is rapid, two possible rate-limiting steps could be the determinants of the long time course of action. These are translocation of the A1 chain from the outside of the cell membrane to its site of action (this includes the time required for separation from the whole toxin) or the availability of NAD+ for activation. When NAD+ concentrations in rat liver were elevated 4-fold, by the administration of nicotinamide, no change in the rate of activation of adenylate cyclase by cholera toxin was observed. Thus the intracellular concentration of NAD+ is not rate-limiting and the major rate-limiting determinant in intact cells must be between the time of toxin binding to the cell membrane and the appearance of subunit A1 at the enzyme site.     

An approximation method for the determination of diffusion and permeability coefficients in nerve trunks

A recently introduced approximation method is applied in order to obtain an expression for the amount of a substance remaining within a nerve at any time, the nerve having been soaked for a long time in a solution containing the substance until the time zero when it is bathed in the same solution but without the substance. The case of a uniform nerve without a sheath leads to substantially the same results as previously obtained by A. V. Hill (1928) for this case. A solution is given for the case of a nerve without sheath but having fibers which are permeable. In this case it is shown how an effective diffusion coefficient for the interstitial fluid can be obtained, as well as the effective inward and outward fiber permeabilities. A solution is given for the case of a nerve with a sheath in which the substance considered does not penetrate the fibers, and it is shown how the effective diffusion coefficients of the sheath and the interstitial fluid can be obtained.     

Sulfate Uptake and Respiration of Aging Potato Discs Modified by Malonic Acid and Ultraviolet Radiation

The time course of sulfate uptake in relation to respiration is shown for aging slices of potato, Solanum tuberosum L. cv. Russet. For comparative purposes, a time course for phosphate uptake is also shown. Malonic acid depressed both the respiratory rise and the sulfate accumulating ability of aging discs. A low dose of ultraviolet radiation given at the onset of aging reduced sulfate uptake by one-half without lowering respiration. We hypothesize that sulfate uptake is controlled by at least two mechanisms: one associated with oxidative metabolism and the other mediated by protein synthesis.