Measurement and analysis of the shape recovery process of each erythrocyte for estimation of its deformability using the microchannel technique: the influence of the softness of the cell membrane and viscosity of the hemoglobin solution inside the cell

This study tried to evaluate the deformability of each erythrocyte by measuring the time constant of shape recovery just after the erythrocytes left the microchannels. We fabricated a microchannel array with a 5μm-square, 100μm-long cross-section on a PDMS sheet. Three different kinds of blood samples were prepared—healthy erythrocytes as a control, artificially membrane-hardened erythrocytes and artificial hemoglobin solution-diluted erythrocytes—to investigate the influence of erythrocyte's mechanical property changes on the time constant of shape recovery. These shape recovery processes were modeled and analyzed by a standard liner solid model. As a result, the temporal variation of the compressive strain of all erythrocytes showed exponential decay with time elapsed like a first order lag system, so the time constant of shape recovery could be calculated from the semi-logarithmic relaxation curve. The stiffer the cell membrane was using glutaraldehyde, the shorter the time constant for relaxation became compared to healthy erythrocytes. The diluted hemoglobin erythrocytes snapped back quicker than healthy ones. In addition, the time constant of healthy blood drawn from females was clearly shorter than that collected from males. However, the time constant of fully hemoglobin substituted erythrocytes was not affected by gender difference. These results indicate that there is not a significant difference in the stiffness of healthy cell membranes regardless of individual and gender differences. On the other hand, the viscosity of the hemoglobin solution inside the cell is one of the significant factors affecting the time constant. Therefore, these results suggest that the deformability of individual erythrocytes can be quantitated by the time constant for relaxation measured by microchannel techniques.     

Aging and the metrics of time

In contrast to clock time, which is extrinsic, universal and reversible, age is an intrinsic, directed measure of the state of a particular system. It is proposed that if the dynamical equations of a given system are cast into canonical form, a time scale intrinsic to that system can be derived. The metric which converts a given intrinsic time to clock time is derived in terms of the given system's constitutive parameters. Age becomes a question of similitude, two systems being in corresponding states (i.e. at the same age) at identical instants of intrinsic time (not clock time).It is further proposed that there is an intrinsic time associated with any dissipative process and that the coupling coefficients, L_ik, of irreversible thermodynamics are metrics which scale the passage of intrinsic time to clock time as measured by a standard harmonic oscillator. Thus in addition to the long standing conjecture that entropy production determines the direction of time's arrow there also is a sense in which it determines the rate of its flow.     

Interoceptive Focus Shapes the Experience of Time

The perception of time is a fundamental part of human experience. Recent research suggests that the experience of time emerges from emotional and interoceptive (bodily) states as processed in the insular cortex. Whether there is an interaction between the conscious awareness of interoceptive states and time distortions induced by emotions has rarely been investigated so far. We aimed to address this question by the use of a retrospective time estimation task comparing two groups of participants. One group had a focus on interoceptive states and one had a focus on exteroceptive information while watching film clips depicting fear, amusement and neutral content. Main results were that attention to interoceptive processes significantly affected subjective time experience. Fear was accompanied with subjective time dilation that was more pronounced in the group with interoceptive focus, while amusement led to a quicker passage of time which was also increased by interoceptive focus. We conclude that retrospective temporal distortions are directly influenced by attention to bodily responses. These effects might crucially interact with arousal levels. Sympathetic nervous system activation affecting memory build-up might be the decisive factor influencing retrospective time judgments. Our data substantially extend former research findings underscoring the relevance of interoception for the effects of emotional states on subjective time experience.     

军标菌株生活史中各阶段生长发育时间的研究

为了更好地研究军标菌在其应用中的实验周期问题 ,采用插片培养法和载片培养法对军标中 5株实验菌的生活史中各阶段生长发育所需时间进行了研究。结果表明 ,5株菌的各时期生长发育所需时间有所不同。整个生活史最长的 4940min ,如AS 3 .42 5 4。最短的 3 888min ,如AS 3 .3 95 0。孢子萌发阶段所需时间也各不相同 ,最长的需 1 5 2 0min ,如AS 3 .3 885。最短的需 640min ,如AS 3 .3 95 0。这一研究为军标中霉菌试验周期 ,即 2 8d过长而且完全可缩短试验周期的观点 ,提供了有力的证据。     

On the time reversal of noise signals

This paper addresses the question of whether, and under what conditions, a noise trace changes its statistical properties when the time axis is reversed in direction. The autocorrelation function of the noise or its power spectrum cannot be used to identify the directionality of time in a noise signal since both are always the same for the signal and for its time reverse, regardless of the characteristics of the noise. However, the autocorrelation function can be generalized to represent the average of the products of powers of the signal at pairs of time instances separated by a given interval. If the powers are not the same for the first and second time instances, the generalized autocorrelation function can detect whether the statistical properties of a noise signal change upon the reversal of the direction of the time axis. We show that noise generated by systems that obey microscopic reversibility, i.e., that are at thermodynamic equilibrium, show the same statistical properties when evaluated forward and backward in time. A noise signal that does not demonstrate such time-reversal behavior discloses that the system that generates it is not at thermodynamic equilibrium. Several model examples are presented for illustration.     

Time discounting and the body mass index: Evidence from the Netherlands

In many Western countries, the relative weight of people -- measured by the body mass index (BMI) -- has increased substantially in recent years, leading to an increasing incidence of overweight and related health problems. As with many forms of risky behavior, it is plausible that overweight is related to the individual discount rate. Increases in credit card debts, the rise in gambling and the development of a more hedonic life style, suggest that the average discount rate has increased over time. An increase in time discounting may be a contributing factor in the rise in BMI. Applying a large set of indicators for the individual discount rate from a Dutch survey, this paper analyzes whether changes in time discounting can account for differences in body mass between individuals at a given point in time and whether changes in the average individual discount rate can explain the remarkable increase in BMI experienced in recent years in the Netherlands. We find some evidence for a link between time discounting and differences in BMI between people, but this relationship depends strongly on the choice of the proxy for the discount rate. Giving our hypothesis the best chance, we analyze the development of the time discounting proxies that are most strongly related to BMI. We find no evidence for a change of these proxies over time. Our main conclusion therefore is that overweight might be related to the way people discount future health benefits, but the increase in BMI is more likely explained by shifts in other parameters that determine the intertemporal decisions regarding the trade-off of current and future health and satisfaction.     

The effect of motor activity on the formation and maintenance of the function of time perception in the course of ontogeny

The effect of motor activity on the perception of the duration of time intervals was studied. Seven hundred and ninety-two subjects aged 7–91 years subjectively measured (scaled) time intervals in the range from 1 to 10 s by methods of estimating, production, and cross-modality matching. The accuracy of scaling was estimated from the value of the relative error. The degree of correspondence of subjective time scales to physical ones was determined from the exponent of the psychophysical scaling function. It was shown that the use of methods with a distinct motor component (production) ensures the smallest error of subjective measurement and the formation of the most adequate subjective time scales. It was found that, for subjects of older age groups, motor activity is a factor that promotes the maintenance of the time perception function.     

Fixation probability for lytic viruses: the attachment-lysis model

The fixation probability of a beneficial mutation is extremely sensitive to assumptions regarding the organism's life history. In this article we compute the fixation probability using a life-history model for lytic viruses, a key model organism in experimental studies of adaptation. The model assumes that attachment times are exponentially distributed, but that the lysis time, the time between attachment and host cell lysis, is constant. We assume that the growth of the wild-type viral population is controlled by periodic sampling (population bottlenecks) and also include the possibility that clearance may occur at a constant rate, for example, through washout in a chemostat. We then compute the fixation probability for mutations that increase the attachment rate, decrease the lysis time, increase the burst size, or reduce the probability of clearance. The fixation probability of these four types of beneficial mutations can be vastly different and depends critically on the time between population bottlenecks. We also explore mutations that affect lysis time, assuming that the burst size is constrained by the lysis time, for experimental protocols that sample either free phage or free phage and artificially lysed infected cells. In all cases we predict that the fixation probability of beneficial alleles is remarkably sensitive to the time between population bottlenecks.     

Delimiting the Location of the Scrapie Prion Incubation Time Gene on Chromosome 2 of the Mouse

Scrapie is a transmissible neurodegenerative disease caused by unusual pathogens called prions. The interval between inoculation and illness for experimental mouse scrapie is dramatically influenced by an incubation time gene (Prn-i) that is linked to Prn-p, the structural gene for prion protein (PrP). Although prion proteins from mouse strains with short and long scrapie incubation times differ by two amino acids, mice with discordant disease phenotype and Prn-p genotype occur in segregating crosses, suggesting recombination between Prn-p and a distinct incubation time locus. In addition, expression of Prn-p(b) transgenes from long incubation time mice shortened, rather than prolonged, incubation time. In this study, mice carrying chromosomes with meiotic crossovers near Prn-p were analyzed for scrapie incubation time phenotype. The results indicated that Prn-i (should it exist) must lie within an interval 0.67 cM proximal and 0.22 cM distal to Prn-p. The results also suggest that the cumulative effects of other genes, rather than meiotic recombination, were responsible for the putative recombinants of earlier studies. However, the effect of Prn-p(b) transgene expression in abbreviating scrapie incubation time was mitigated when the transgenes were transferred to mice with an endogenous long incubation time allele. Thus, Prn-p(b) transgenes and Prn-i may modulate scrapie pathogenesis by different mechanisms.     

Effect of ablation of the septum pellucidum on the marking of time intervals

It is shown that preliminary ablation of the septum lucidum (the rat group II) leads to a considerable (up to 1000 presentations) and prolonged (up to one year) worsening of the elaboration of time intervals estimation, as compared to intact animals and does not significantly influence the conditioned reflexes to time stabilized before the operation (the rat group I). The great worsening of time intervals estimation is due to disturbance of the very mechanism of the reflex to time. Differences are discussed between the two groups of the operated rats. The septum ablation does not affect the state of conditioned reflexes to present stimuli. In the greater part of the postoperative rats a lowering of alimentary motivation is observed that may be secondarily accompanied by a disturbance of time intervals estimation.     

Investigations of the Geotropic Curvature of the Avena Coleoptile

The geotropic reaction in Avena coleoptiles is studied as a function of the stimulation time. The direction of the stimulation with respect to the vascular bundles must be defined when studying geotropic responses. It is found that the threshold time to evoke geotropic response is less than half a minute, i.e., at least ten times lower than the presentation time usually reported in the literature. An extrapolation procedure can be used to give a so-called extrapolated presentation time t_b, which is intimately related to the logarithmic part of the geotropic response curve and has a physical meaning in the reciprocity rule. The problem of the duration of the true threshold time for stimulation with 1 g is discussed. An experiment indicates that it is not necessary for mass particles (“statoliths”) to settle on the lateral cell wall in order to start the geotropic reaction chain. The slope of the logarithmic part of the geotropic response curve is independent of the transverse force applied to the coleoptiles. Support is given to the view that the slope is determined by the number of sedimenting mass particles.     

Modeling the hazard of transition into the absorbing state in the illness-death model

The illness-death model is the simplest multistate model where the transition from the initial state 0 to the absorbing state 2 may involve an intermediate state 1 (e.g., disease relapse). The impact of the transition into state 1 on the subsequent transition hazard to state 2 enables insight to be gained into the disease evolution. The standard approach of analysis is modeling the transition hazards from 0 to 2 and from 1 to 2, including time to illness as a time-varying covariate and measuring time from origin even after transition into state 1. The hazard from 1 to 2 can be also modeled separately using only patients in state 1, measuring time from illness and including time to illness as a fixed covariate. A recently proposed approach is a model where time after the transition into state 1 is measured in both scales and time to illness is included as a time-varying covariate. Another possibility is a model where time after transition into state 1 is measured only from illness and time to illness is included as a fixed covariate. Through theoretical reasoning and simulation protocols, we discuss the use of these models and we develop a practical strategy aiming to (a) validate the properties of the illness-death process, (b) estimate the impact of time to illness on the hazard from state 1 to 2, and (c) quantify the impact that the transition into state 1 has on the hazard of the absorbing state. The strategy is also applied to a literature dataset on diabetes.     

High-throughput Analysis of Ultrasonication-forced Amyloid Fibrillation Reveals the Mechanism Underlying the Large Fluctuation in the Lag Time

Amyloid fibrils form in supersaturated solutions of precursor proteins by a nucleation and growth mechanism characterized by a lag time. Although the lag time provides a clue to understanding the complexity of nucleation events, its long period and low reproducibility have been obstacles for exact analysis. Ultrasonication is known to effectively break supersaturation and force fibrillation. By constructing a Handai amyloid burst inducer, which combines a water bath-type ultrasonicator and a microplate reader, we examined the ultrasonication-forced fibrillation of several proteins, with a focus on the fluctuation in the lag time. Amyloid fibrillation of hen egg white lysozyme was examined at pH 2.0 in the presence of 1.0–5.0 M guanidine hydrochloride (GdnHCl), in which the dominant species varied from the native to denatured conformations. Although fibrillation occurred at various concentrations of GdnHCl, the lag time varied largely, with a minimum being observed at ∼3.0 m, the concentration at which GdnHCl-dependent denaturation ended. The coefficient of variation of the lag time did not depend significantly on the GdnHCl concentration and was 2-fold larger than that of the ultrasonication-dependent oxidation of iodide, a simple model reaction. These results suggest that the large fluctuation observed in the lag time for amyloid fibrillation originated from a process associated with a common amyloidogenic intermediate, which may have been a relatively compact denatured conformation. We also suggest that the Handai amyloid burst inducer system will be useful for studying the mechanism of crystallization of proteins because proteins form crystals by the same mechanism as amyloid fibrils under supersaturation.     

Temporal pattern in consumption of the first drink of the day in alcohol-dependent persons

Loss of control over drinking and the craving for alcohol are cardinal signs of alcohol dependence. Our clinical practice indicates that these cravings do not occur randomly during the day, but at the same times each day for the same patient. To validate this hypothesis that alcohol-dependent patients have a circadian rhythmic craving in their desire for their first drink of the day, we asked 217 persons diagnosed as alcohol-dependent according to DSM-IV criteria to complete a questionnaire that surveyed whether this craving occurred at a fixed time each day. Of the respondents, 82% reported it did; 87% of them could state the time of day they consumed their first daily drink; and 80% reported that the time of their first drink of the day did not vary much from one day to the next. The most frequent time of consuming the first drink of alcohol was between 09:00 and 11:00 h, and it was independent of the subjects' sleep-wake routine (the delay between the hours of wake-up and the time of the first urge for alcohol was 3:45 +/- 3:30 h) and lunch or dinner time. This rhythmicity seems to be a pertinent criterion for alcohol dependence syndrome.     

Circannual Variations of the Bleeding Time in the Rat

This study was carried out to determine the annual fluctuations of the tail bleeding time in the rat. Bleeding time was determined by transection of the tail of pentobarbital-anesthetized rats. Over a 6-year period, monthly measurement of the tail bleeding time revealed highly reproducible circannual fluctuations. Bleeding times were shortened in the summer (414 ± 18 s in July), being almost half that observed during the winter span (886 ± 32 s in January). The difference between these two time points was highly significant (p > 0.001). This study reports for the first time circannual variations of the bleeding time in the rat.     

Daily restricted feeding resets the circadian clock in the suprachiasmatic nucleus of CS mice

Circadian rhythms in clock gene expressions in the suprachiasmatic nucleus (SCN) of CS mice and C57BL/6J mice were measured under a daily restricted feeding (RF) schedule in continuous darkness (DD), and entrainment of the SCN circadian pacemaker to RF was examined. After 2-3 wk under a light-dark cycle with free access to food, animals were released into DD and fed for 3 h at a fixed time of day for 3-4 wk. Subsequently, they returned to having free access to food for 2-3 wk. In CS mice, wheel-running rhythms entrained to RF with a stable phase relationship between the activity onset and feeding time, and the rhythms started to free run from the feeding time after the termination of RF. mPer1, mPer2, and mBMAL1 mRNA rhythms in the SCN showed a fixed phase relationship with feeding time, indicating that the circadian pacemaker in the SCN entrained to RF. On the other hand, in C57BL/6J mice, wheel-running rhythms free ran under RF, and clock gene expression rhythms in the SCN showed a stable phase relation not to feeding time but to the behavioral rhythms, indicating that the circadian pacemaker in the SCN did not entrain. These results indicate that the SCN circadian pacemaker of CS mice is entrainable to RF under DD and suggest that CS mice have a circadian clock system that can be reset by a signal associated with feeding time.     

Characterization of hydrotropism: the timing of perception and signal movement from the root cap in the agravitropic pea mutant ageotropum

In this study, ageotropum pea mutant was used to determine the threshold time for perception of an osmotic stimulation in the root cap and the time requirement for transduction and transmission of the hydrotropic signal from the root cap to the elongation region. The threshold time for the perception of an osmotic stimulation was compared to current estimates of threshold times for graviperception in roots. The time required for transduction and transmission in the hydrotropic response of ageotropum was compared to the time requirement in the gravity response of Alaska pea roots. We determined that threshold time for perception of an osmotic stimulation in the root cap is very rapid, occurring in less than 2 min following the application of sorbitol to the root cap. Furthermore, a single 5 min exposure of sorbitol to the root cap fully induced a hydrotropic response. We also found that transduction and transmission of an osmotic stimulus requires 90-120 min for movement from the root cap to more basal tissues involved in differential growth leading to root curvature. The very rapid threshold time for perception of root hydrotropism is similar to those times reported for root gravitropism. However, the time required for the transduction and transmission of an osmotic stimulation from the root cap is significantly longer than the time required in gravitropism. These results suggest that there must exist some differences between root hydrotropism and gravitropism in either the rate or mechanisms of transduction and transmission of the tropistic signal from the root cap.     

Initial conditions and the kinetics of the sodium conductance in Myxicola giant axons. I. effects on the time-course of the sodium conductance

The effects of conditioning polarizations, ranging from--150 to 0 mV and of durations from 50 mus to 30 ms, on the time-course of GNa during test steps in potential were studied in Myxicola giant axons. Beyond the effects of conditioning polarizations on the amplitude of GNa, the only effect was to produce a translation of GNa(t) along the time axis without a change in shape. For depolarizing conditioning potentials, Hodgkin-Huxley kinetics predict time shifts about threefold greater than found experimentally, whereas the predictions of the coupled model of Goldman (1975. Biophys. J. 15:119--136) were in approximate agreement with our experiments. The time shifts developed over an exponential time-course as the conditioning pulse duration was increased. The time constant of development of the time shift was considerably faster than, and showed the opposite dependency on potential from, the values predicted by both models. It had a mean Q10 of 1/2.50. This fast activation process cannot account for the observed rise time behavior of GNa, suggesting that there is an additional activation process. All results are consistent with the idea that the gating structure displays more than three states, with state intermediate between rest and conducting.     

Sharing the joke: the size of natural laughter groups

Recent studies suggest that laughter plays an important role in social bonding. Human communities are much larger than those of other primates and hence require more time to be devoted to social maintenance activities. Yet, there is an upper limit on the amount of time that can be dedicated to social demands, and, in nonhuman primates, this sets an upper limit on social group size. It has been suggested that laughter provides the additional bonding capacity in humans by allowing an increase in the size of the “grooming group.” In this study of freely forming laughter groups, we show that laughter allows a threefold increase in the number of bonds that can be “groomed” at the same time. This would enable a very significant increase in the size of community that could be bonded.     

An empirical link between the spectral colour of climate and the spectral colour of field populations in the context of climate change

1. The spectral colour of population dynamics and its causes have attracted much interest. The spectral colour of a time series can be determined from its power spectrum, which shows what proportion of the total variance in the time series occurs at each frequency. A time series with a red spectrum (a negative spectral exponent) is dominated by low-frequency oscillations, and a time series with a blue spectrum (a positive spectral exponent) is dominated by high-frequency oscillations. 2. Both climate variables and population time series are characterised by red spectra, suggesting that a population's environment might be partly responsible for its spectral colour. Laboratory experiments and models have been used to investigate this potential link. However, no study using field data has directly tested whether populations in redder environments are redder. 3. This study uses the Global Population Dynamics Database together with climate data to test for this effect. We found that the spectral exponent of mean summer temperatures correlates positively and significantly with population spectral exponent. 4. We also found that over the last century, temperature climate variables on most continents have become bluer. 5. Although population time series are not long or abundant enough to judge directly whether their spectral colours are changing, our two results taken together suggest that population spectral colour may be affected by the changing spectral colour of climate variables. Population spectral colour has been linked to extinction; we discuss the potential implications of our results for extinction probability.