Effect of negative pions,relative to 140 kV - 29 MeV photons and 20 MeV electrons,on proliferation of Ehrlich ascites carcinoma cells

Summary The effect of negative pions (peak and plateau), photons (140 kV and 29 MeV), and 20 MeV electrons on the proliferative capacity of Ehrlich ascites carcinoma cells was investigated. Proliferative survival curves plotted for the modalities employed are presented. Under the experimental conditions used, the peak pions were more effective than plateau pions by a factor of about 1.4. For 50% survival, 140 kV X-rays had the same effect as peak pions but the latter was more effective (factor 1.2) at 10% survival level. When 140 kV X-rays were taken as the standard, following are the RBE values calculated at 50% survival level: plateau pions -0.73; peak pions -about 1.0; 29 MeV photons -0.73 and 20 MeV electrons -0.6. The results obtained are compared with those reported on other tumor systems and biological test objects.     

Repair of potentially lethal damage in unfed plateau phase cultures of Ehrlich ascites tumour cells. II. Monolayer cultures

Monolayer cultures of EAT cells when plated immediately after irradiation show a desrease in survival as they "age" in the plateau phase of growth. This decrease, which is manifest as a diminution of the shoulder width of the survival curve down to values approaching zero, is reversible if the cells are kept in their growth medium for some hours after irradiation before trypsinization and plating. Survival curves obtained by this holding procedure are similar in shape to those shown by exponentially growing or early plateau phase cells. We interpret this effect in terms of repair of potentially lethal damage which occurs after immediate plating in young cultures but only declared during plating in cultures which have "aged" in the plateau phase. The kinetics of this repair and the effects caused by the addition of serum after irradiation in the cultures have been studied.     

Radiobiological data for clinical dosimetry in pion tumour therapy

Summary Ehrlich ascites tumour cells were irradiated with negative pions at different positions in the plateau and the peak of the depth absorbed dose curve. Dose-survival curves for immediate testing of the viability of the cells are given and are compared with other types of radiations in use for therapy. From the data obtained after repair of potentially lethal damage effective survival curves for fractionated irradiation are evaluated.     

Review article. The dynamics of seed mortality

The shape of seed mortality curves in dry storage, and the dynamics of seed ageing are discussed as they help to define the rate-controlling processes. Emphasis is placed on distinguishing between two types of survival curves: those which show an initial period of relatives stability preceding a dynamic rate of cumulative mortality, and those in which an initial period of relative stability is lacking. The fact that the survival curves had to be modelled separately for the initial plateau phase and for the sigmoid phase, support the contention that there are two phases of seed ageing. The factors operating in these two sectors are discussed and the glassy state in seeds is suggested to serve as a stabilizer, particularly as it may contribute to the period of relative stability. The rapid progress of deterioration during the dynamic period may represent a weakening of the glassy state, combined with a facile hydrolysis of sugar components and the unleashing of an array of oxidative processes. A recognition of the distinction between the period of relative stability and the period of dynamic deterioration may provide new insights about seed longevity and deterioration.     

Dose fractionation effects in plateau-phase cultures of C3H 10T1/2 cells and their transformed counterparts

A comparison of gamma-ray dose fractionation effects was made using plateau-phase cultures of C3H 10T1/2 cells and their transformed counterparts in an attempt to simulate basically similar populations of cells that differ primarily in their turnover rates. The status of cell populations with respect to their turnover rates may be an important factor influencing dose fractionation effects in early- and late-responding tissues. In this cell culture system, the rate of cell turnover was approximately three times higher for the plateau-phase transformed cultures. While the single acute dose survival curves for log-phase cells were indistinguishable, there were significant differences between the survival curves for plateau-phase cultures of the two cell types. These differences were qualitatively similar to the differences recently postulated for the survival of target cells governing early and late tissue responses. Both cell lines had a similar capacity for repair of sublethal damage, but untransformed cells had a much greater capacity to repair potentially lethal damage in plateau phase. Further, untransformed plateau-phase cultures were much more sensitive to a radiation-induced G1 (or G0 to G1) delay than transformed cultures. Multifraction survival curves were determined for both cell lines for doses per fraction ranging from 9.0 to 0.8 Gy, and from these isoeffect curves of log total dose versus dose per fraction were derived. The isoeffect curve for the slowly cycling, untransformed cells was found to be appreciably steeper than that for the more rapidly cycling transformed cells, a finding consistent with previously reported differences in dose fractionation isoeffect curves for early- and late-responding tissues in vivo.     

小麦种子在不同保存条件下的生活力丧失特性研究

近年来种子在低温种质库和室温保存条件下的生活力丧失特性研究日益受到关注,但是与其重要性相比,目前很少见有文献报道此方面进展。本文中我们监测了在中期库、室温和人工加速老化条件下小麦种子的生活力变化,以了解种子在这些保存条件下的生活力变化特性。结果表明,三种条件下所有种子的存活曲线均呈反S形,这种特点不受保存条件的影响。随着保存温度的降低,种子生活力丧失速度降低,反S形曲线的平台期和种子寿命延长。我们采用T检验来判断平台期和种子生活力快速下降期之间的转折点（Pt）,发现小麦种子在不同条件下保存时,其Pt均十分接近,在82.2%到83.6%之间。本文讨论了将Pt以及其他生理指标作为种子保存过程中生活力快速下降的预警指标的可能性。     

A minimally parametrized branching process explaining plateau phase of qPCR amplification

Quantitative polymerase chain reaction (qPCR) is a commonly used molecular biology technique for measuring the concentration of a target nucleic acid sequence in a sample. The whole qPCR amplification process usually consists of an exponential, a linear and a plateau phase. In qPCR experiments, amplification curves of samples with different template concentrations often, even though not always, have the same plateau height. The biological theory for this phenomenon is that the plateau height is determined by reaction kinetics. Does it mean that the target concentration has no effect on the final plateau height? We proposed a branching process based on Michaelis–Menten kinetics. Our model can describe all phases of qPCR amplification despite its simplicity (it depends on only one parameter). We theoretically showed, through almost sure convergence, that amplification curves will eventually plateau at finite values in any experiment, under any condition. We conclude that the plateau height is largely determined by reaction kinetics but could also be affected by the template concentration. This is in accordance with the current biological theory.

     

Discrepancies between patterns of potentially lethal damage repair in the RIF-1 tumor system in vitro and in vivo

Repair of potentially lethal damage (PLD) was studied in the RIF-1 tumor system in several different growth states in vivo and in vitro. Exponentially growing, fed plateau, and unfed plateau cells in cell culture as well as small and large subcutaneous or intramuscular tumors were investigated. Large single doses of radiation followed by variable repair times as well as graded doses of radiation to generate survival curves immediately after irradiation or after full repair were investigated. All repair-promoting conditions studied in vitro (delayed subculture, exposure of cells to depleted growth medium after irradiation) increased surviving fraction after a single dose. The D0 of the cell survival curve was also increased by these procedures. No PLD repair was observed for any tumors irradiated in vivo and maintained in the animal for varying times prior to assay in vitro. The nearly 100% cell yield obtained when this tumor is prepared as a single-cell suspension for colony formation, the representative cell sample obtained, and the constant cell yield per gram as a function of time postirradiation suggest that this discrepancy is not an artifact of the assay system. The most logical explanation of these data and information on radiocurability of this neoplasm is that PLD repair, which is so frequently demonstrated in vitro, may not be a major factor in the radioresponse of this tumor when left in situ.     

基于标志重捕法的高原鼢鼠种群动态及其环境影响因子

高原鼢鼠（Eospalax baileyi）是青藏高原优势地下啮齿动物,研究其种群数量变化规律及其与环境因子关系,对于保护高寒草地生物多样性和科学防控草原鼠害具有重要意义。于2014-2019年在天祝县抓喜秀龙乡高原鼢鼠分布区,采用标志重捕法调查每年5月和10月高原鼢鼠种群密度、存活率、补充量及体重,利用样方法调查各植物功能群地上、地下生物量,并从中国气象数据中心获取同期气象数据。通过灰色关联度分析,探究高原鼢鼠种群特征变化与环境因子关联程度。结果表明：高原鼢鼠种群数量存在年际和季节性变化规律,年际间高原鼢鼠种群数量总体呈下降趋势,秋季高原鼢鼠种群数量高于春季种群数量;灰色关联分析表明,春季高原鼢鼠种群数量变化与降雨量、极端温度和杂类草生物量关联程度较高,而秋季高原鼢鼠种群数量与环境因子关联程度较低。研究结果不仅为今后构建高原鼢鼠种群数量预测预报模型提供基础依据,也为适时防控高原鼢鼠危害提供有益参考。     

Radiosensitivity of the cells of an established human melanoma cell line and the parent melanoma xenograft

Survival curves of cells from a human melanoma xenograft (E.F.) and a cell line (FME) established from this xenograft were determined. The cells of the established line were harvested from exponentially growing cultures, plateau phase cultures or solid tumours in athymic mice (FME-X) before irradiation. During irradiation the cells were kept suspended in culture medium. The colony forming ability of the cells was assayed in soft agar. The Do-value was significantly higher for the parent xenograft than for the established line, whether grown in vitro or in vivo (p less than 0.0001). In addition, the Dq-value was significantly lower for the xenograft than for exponentially growing cultures of the established line (p less than 0.05). Thus the radiation response of the cells of the established line was not representative for that of the cells from the parent xenograft. It is concluded that survival curves for established cell lines should be used with great caution in attempts to predict the radiocurability of human tumours of corresponding histological type.     

Comparison of mechanical properties of orthodontic nickel-titanium wires]

Two packages each, containing 10 wires per package, of different batches of 25 different types of orthodontic archwires made of super-elastic nickel-titanium alloys measuring 0.41 x 0.56 mm2, were investigated. The wires were characterized by obtaining the following measurements at an ambient temperature of 37 degrees: a three-point bending test with the supporting points spaced 10 mm apart, and determination of the torque/bending angle curves using a pure bending test. The force/deflection curves provided the parameters characterizing the super-elastic unloading plateau: average force, slope and endpoint. From the torque/bending angle curves, the parameters average torque, plateau endpoint and the elasticity parameters were determined. Average force (0.8-4.5 N), endpoint (0.2-0.9 mm) and the slope of the unloading plateau (0.2-2.1 N/mm) of the three-point bending test clearly differed for individual wires. Significant differences were also seen for average torque (1.5-11.5 Nmm), unloading plateau endpoint (2.7-20.0 degrees) and elasticity parameters epsilon 4, E4, E5 and E6 in the pure bending test. Individual batches showed only minor differences. The results permit the conclusion to be drawn that super-elasticity is applicable to only a small portion of the wires examined. Although other wires showed super-elastic behaviour, the unloading plateaus has a force level of up to 6 N, and cannot be recommended for orthodontic application. The super-elastic plateau is often of use only for deflections greater than 1.5 mm. The use of super-elastic archwires made of nickel-titanium alloys makes sense only when the elastic properties of the respective wires are known. This makes the provision by the manufacturer of relevant data on the elastic properties of wires a necessity.     

Repair of potentially lethal X-ray damage in fibroblasts derived from patients with hereditary and D-deletion retinoblastoma

We examined X-ray induced potentially lethal damage repair (PLDR) in density inhibited plateau phase cultures of six fibroblast strains derived from patients with hereditary retinoblastoma and two patients with D-deletion retinoblastoma and compared them to three normal controls. PLD was measured in hereditary retinoblastoma (7 Gy exposure) and normal cells (7 and 9 Gy exposure) after 24 h repair time. PLD survival curves were performed at 2-9 Gy on six retinoblastoma and three normal control cell strains. Thus, PLDR was compared at equitoxic survival levels as well as after exposure to equal doses of radiation. Some retinoblastoma strains showed normal PLDR whereas others were possibly deficient. Implications of PLDR for susceptibility to radiation-induced and spontaneous tumours in hereditary retinoblastoma patients are discussed.     

Interaction between prostaglandins and calcium: The importance of bell-shaped dose-response curves

Biological response to PGs show two basic forms of dose/response relationship, plateau and bell-types. although bell-shaped dose/response curves are well documented their possible occurrence is almost always ignored on the design and interpretation of experiments on PGs and related substances. This may lead to serious errors, several types of which are described. The ignoring of a well-documented phenomenon may take place because there is no accepted hypothesis which attempts to explain the bell-type curves. A hypothesis is proposed which accounts for both plateau and bell type responses. It is developed primarily with respect to PG-calcium interactions but may be applicable to some PG-cyclic nucleotide interactions as well. The model leads to precise predictions which can be experimentally tested in many systems.     

Evidence for reduced capacity for damage accumulation and repair in plateau-phase C3H 10T1/2 cells following multiple-dose irradiation with gamma rays

The effects of multiple-dose gamma irradiation on the shape of survival curves were studied with mouse C3H 10T1/2 cells maintained in contact-inhibited plateau phase. The dose-fractionation intervals included 3, 6, and 24 h. Following three fractionated doses (5 Gy per dose) of exposures, cells responded to further irradiation by displaying a survival curve with a much reduced shoulder width (Dq) compared to that of the survival curve measured in cells irradiated with single-graded doses alone. The effect on the mean lethal dose (D0) was small and appeared to be significant. The effect on reduction of Dq could not be completely overcome by lengthening the fractionation intervals from 3 to 6 h or 24 h, times in which repair of sublethal damage (SLD) measured by simple split-dose scheme and potentially lethal damage (PLD) measured by postirradiation incubation was completed. Other experiments showed that pretreatments of cells with fractionated irradiation appeared to slow down the cellular repair processes of SLD and PLD. Therefore, the observed change in the shape of survival curves after fractionation treatments may be attributed to a reduction of the cells' capacity for damage accumulation by an enhancement of the lethal expression of SLD and PLD. Although the molecular mechanism(s) is not known, the results of this study indicate that the acute graded dose-survival curve cannot be used a priori to extrapolate and reliably predict results of hyperfractionation. It is probable that for a nondividing or slowly dividing cell population, such an extrapolation may lead to an underestimation of cell killing. Furthermore, the findings of this investigation appear to support an interpretation, alternative to the high-linear energy transfer (LET) track-end postulate, for the effects on cell survival seen at low doses or low dose rates.     

Studies on the reaction mechanism of DT diaphorase. Intermediary plateau and trough regions in the initial velocity vs substrate concentration curves.

The steady-state kinetics of DT diaphorase [NAD(P)H dehydrogenase (quinone): EC 1.6.99.2]from rat liver has been studied using 2,6-dichloroindophenol as electron acceptor and NADH as electron donor. The υ vs [S]curves revealed intermediary plateau and “trough” regions when NADH and dichloroindophenol were the varying substrates. It has been demonstrated by statistical analysis that equations involving fourth-power terms of the substrate concentrations are able to describe the “trough.” These equations have been previously shown in the literature to be capable of describing intermediary plateau regions also. Changes in protein concentration did not affect these curves substantially, whereas changes in pH caused shifts in the positions of their intermediary plateau regions. Increase of the ionic strength by addition of 0.25–0.5 m KCl changed the intermediary plateau region into a “trough” in the υ vs [NADH] plot, whereas the “trough” of the υ vs [dichloroindophenol]plot was transformed into an intermediary plateau. Changes in the temperature of the assay system also led to changes in the kinetic curves. Incubation of the enzyme at 23 °C for 150 min caused disappearance of the intermediary plateau and “trough” regions in the υ vs [NADH]or [dichloroindophenol]plots, respectively. These appeared again after cooling at 0 ° C.The effect of pH, ionic strength, and temperature are discussed within the framework of two main models chosen by statistical analysis: (1) the reaction is catalyzed by a four-site enzyme exhibiting positive and negative cooperativity with respect to the catalytic (kinetic) activity of the sites involved; (2) two enzyme species each possessing two sites are present. These two are either independent or interconnected via a slow isomerization step.     

Complex type of kinetics of fructose-1,6-diphosphate from the rat and rabbit liver

Studies on rat and rabbit liver fructose 1.6-bisphosphatase inhibition by AMP showed that with an increase in EDTA concentration the hyperbolic AMP inhibition curve is transformed into a sigmoidal one. At intermediate EDTA concentrations, the kinetic curves have a plateau. The appearance of the intermediate plateau may be due to the superposition of kinetic curves corresponding to two enzyme forms simultaneously present in the assay mixture. One of these forms deprived of endogenous Me2+ (presumably Zn2+) is inhibited by AMP in a cooperative manner, while the other one retains Me2+ which prevents the cooperative response of the enzyme to AMP.     

Effect of negative pi mesons on vascular permeability of brain in neonatal rats

Summary Neonatal rats and their radiation-induced cerebral petechial hemorrhages were used as an experimental system for evaluating the effects of negative pions on healthy tissue and especially on the microvasculature. Dose response curves for peak and plateau pions (dose range 150–250 rad and 100–400 rad, respectively) were obtained and compared with those of 200 kV X-rays of corresponding dose rates. The RBE of the peak pions was 1.1, that of the plateau pions 0.6 resulting in a peak/plateau ratio of 1.8. Implications were made as to the importance of this favorable peak/plateau relationship since the response of the capillary endothelium to pion-irradiation might be one of the limiting factors in radiotherapy.     

Membrane dynamic alterations associated with viral transformation and reversion. Decay of fluorescence emission and anisotropy studies of 3T3 cells.

Fluorescence lifetimes, anisotropies and rotational correlation time values of 1,6-diphenyl-1,3,5-hexatriene (DPH) in membranes of normal, transformed, and revertant 3T3 cells were determined by nanosecond (nsec), photon counting spectrofluorimetry. No change in lifetime values with transformation or reversion is observed. Fluorescence anisotropy decay curves show at least two components; an initial relatively fast decay and a non-zero “plateau” level component. The observed changes in the average anisotropy values, which qualitatively follow steady-state fluorescence polarization values, is due primarily to changes in the non-zero “plateau” level component. The anisotropy decay curves suggest that the rotational motion of the probe is restricted to a limited angular range. The present results are compared with model membrane systems.     

A novel procedure for identification of the folding/unfolding patterns of dimeric proteins

The unfolding of proteins has been widely used for investigating the thermodynamic properties of monomeric proteins but has been used infrequently for dimeric (or oligomeric) proteins, because of the inherent cooperation of denaturation and dissociation of the dimers (oligomers). Here, we introduce a thermodynamic parameter K_obs to discriminate the diverse folding patterns of dimeric proteins. K_obs remains constant as the protein concentration increases for the true one-step curve of unfolding pattern (A), increases and reaches a plateau for one-step curves with monomeric intermediate pattern (B), and increases steadily with no plateau for one-step curves with dimeric intermediate pattern (C).