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Context: Although ZAP-70 is required for T-cell development, it’s unclear how this kinase controls both positive and negative selection.

Objective and methods: Using OT-I pre-selection thymocytes and a panel of peptide major histocompatibility complex (pMHC) ligands of defined affinity, the recruitment, phosphorylation and activity of ZAP-70 was determined at the interface with antigen-presenting cells (APCs).

Results: pMHC ligands promoting negative selection induce a discrete elevation of ZAP-70 recruitment, phosphorylation and enzymatic activity in the thymocyte:APCs interface.

Discussion: The quantity of ZAP-70 kinase activity per cell is a key parameter controlling the fate of a developing thymocyte since partial inhibition of ZAP-70 kinase activity converted negative into positive selection. Surprisingly, the amount of ZAP-70 enzymatic activity observed during negative selection is not controlled by differential phosphorylation of the ZAP-70 protein but rather by the total amount of T-cell receptor and co-associated ZAP-70 recruited to the thymocyte:APC interface.

Conclusions: These data provide evidence that a burst of ZAP-70 activity initiates the signaling pathways for negative selection.  相似文献   

3.
The spatial distribution of the eggs, larvae, pupae and adults of the wheat-bulb fly was investigated by fitting 42 sets of data comprising 1334 samples to the Poisson and negative binomial distributions, and by using the power law (S2=amb). In general, the tests indicated that all stages were aggregated and fitted the negative binomial model.  相似文献   

4.
The measurement of departure from randomness in spatial distributions has widespread application in ecological work. Several “indices of non-randomness” are compared with regard to their dependence on sample number, sample size and density. Criteria for the best choice of index for specific situations are discussed. A new coefficient Cx is proposed for use with positively contagious distributions and tests of significance are given. When Cx and another index (S2/m−1) are used for positive and negative contagion respectively, values ranging from −1 through 0 (random) to +1 are obtained, regardless of sample number, sample size or density.  相似文献   

5.
Shiyomi (1967a and b) proposed two models which describe the reproduction and the plant-to-plant movement of aphids. For the explanation of the whole process of development of population of aphids, the above two models were incorporated into a new model (called Model C). This model is superior in the following points to the negative binomial model:
  1. Model C has 7 parameters and gives a fuller explanation compared with the negative binomial model which has 2 parameters.
  2. Model C describes the structure of population at any stage of its development, while the negative binomial model describes that of a well developed stage of population.
  相似文献   

6.
The index , which takes the value of −1 for a perfectly regular distribution, +1 for a highly aggregated distribution and 0 for the distribution implied by the theoretical varianceσ2, is proposed and a significance table provided.  相似文献   

7.
目的为研究肢体负压疗法的疗效及探讨其作用机理,我们对犬后肢进行实验研究。方法。实验犬分三组,治疗组为左后肢缺血模型犬并行患者肢负压治疗;对照组同治疗组但不做治疗:自身对照组为双后肢缺血模型犬,左侧行负压治疗,右侧作为对照。  相似文献   

8.
Summary As a part of serial study on population dynamics of the chestnut gall-wasp,Dryocosmus kuriphilus, analyses of the distribution of eggs, gall-cells and emergent holes were made from the statistical point of view. Many of distributions of the eggs per bud could be described by the truncated Poisson, but some cases showed slight overdispersion than expected by chance. Because of no linear increase of with increasing (expected mean for complete sample), however, the truncated negative binomial seemed to be not so available for whole series. Distributions of the gall-cells and the emergent holes were, on the other hand, well described by the truncated Poisson distribution when the observed frequency was calculated for respective trees. Negative-binomial tendency found in distributions from some stations consisted of a certain number of trees would be resulted from mixture of Poisson populations with different means. Random or slightly concentrated oviposition and random mortality within galls was thus supposed for future study unless the proof favouring other distribution models would appear.  相似文献   

9.
Spatial distribution pattern of the brown planthopper (BPH) was analyzed at 9 experimental fields in the northern part of West Java during two consecutive rice cropping seasons, i.e., wet and dry seasons. The population of each developmental stage and wing form of BPH at each location showed consistent departure from the random (Poisson) distribution, the variances of the densities in most cases exceeding their means. Namely, the distribution pattern of BPH per hill of rice plant was found to have a general tendency to be aggregated or contagious and to fit fairly well to the negative binomial model. The tendency for aggregation was further confirmed by both the β-values of -m regression being larger than unity and the CA-values being larger than zero for each developmental stage. Although significant variations in the distribution pattern as measured by β- or CA-value were observed between different developmental stages, between wing forms and among locations, the degree of aggregation for a given developmental stage at each experimental field remained fairly stable throughout the crop period, despite wide temporal changes in population density. Possible factors to explain these characteristics of the spatial distribution pattern of the BPH in West Java were discussed with reference to the process generating it.  相似文献   

10.
To investigate the relation between the distribution pattern of eggs and the parental density in the common cabbage butterfly, Pieris rapae crucivora, the countings of egg number per plant were made on both cabbage plants cultivated in the farm and planted in the net house in which the female butterflies were released at various densities. The frequency distribution of eggs fits well to the negative binomial excepting the cases where they agree withPoisson series, and the degree of aggregation expressed as the reciprocal of the parameter, 1/k, tends to decrease as the egg or parental density increases. At the same parental density, however, the distribution of eggs can be described by the negative binomial with a common parameter, kc, regardless of the difference in the density of laid eggs. In the case where a single female butterfly lays eggs, the spatial pattern of egg distribution is always lean, while its frequencies conform toPoisson or the negative binomial series. This lean changes toward patchy with increasing the parental density. From these results, it is concluded that the degree of aggregation in the distribution of eggs decreases with the increase of the parental density.  相似文献   

11.
Our previous studies indicated that 111In-diethylenetriaminepentaacetic acid (111In-DTPA)-octreotide derivatives with an additional negative charge by replacing N-terminal d-phenylalanine (d-Phe) with an acidic amino acid such as l-aspartic acid (Asp) or its derivative exhibited low renal radioactivity levels when compared with 111In-DTPA-d-Phe1-octreotide. On the basis of the findings, we designed, synthesized and evaluated two Asp-modified 111In-DTPA-conjugated octreotide derivatives, 111In-DTPA-Asp1-octreotide and 111In-DTPA-Asp0-d-Phe1-octreotide. While 111In-DTPA-Asp1-octreotide showed negligible AR42J cell uptake, 111In-DTPA-Asp0-d-Phe1-octreotide exhibited AR42J cell uptake similar to that of 111In-DTPA-d-Phe1-octreotide. When administered to AR42J tumor-bearing mice, 111In-DTPA-Asp0-d-Phe1-octreotide exhibited renal radioactivity levels significantly lower than did 111In-DTPA-d-Phe1-octreotide at 1 and 3 h post-injection. No significant differences were observed in tumor accumulation between 111In-DTPA-Asp0-d-Phe1-octreotide and 111In-DTPA-d-Phe1-octreotide after 1 and 3 h injection. The findings in this study suggested that an interposition of an Asp at an appropriate position in 111In-DTPA-d-Phe1-octreotide would constitute a useful strategy to develop 111In-DTPA-d-Phe1-octreotide derivatives of low renal radioactivity levels while preserving tumor accumulation.  相似文献   

12.
Bacteriorhodopsin and Halorhodopsin present in Halobacterium halobium strains have been investigated in relation to Na+/H+ exchange in isolated cell envelope vesicles. Upon illumination, these retinal proteins result in extrusion of sodium ions by either an electrogenic Na+/H+ antiporter and/or a direct sodium pump. Since a molecular characterization of these mechanism(s) of sodium extrusion has not yet been realized, it was of interest to measure directly the light- and sodium-dependent changes in ΔpH and membrane potential under nearly identical conditions in S9 and R1mR cell membrane vesicles to gain information on the relation of these retinal proteins to sodium extrusion. These activities were evaluated in terms of their dependence on light intensity, and on the inhibitory effect of chemical modifiers of carboxyl groups (carbodiimides); electroneutral exchanges (monensin and triphenyltin); digitoxin and some analogues; and phloretin. Under most of the conditions and treatments employed, light- and sodium-dependent ΔpH led to similar effects in both membrane vesicle types. Hence, it is concluded that the ΔpH and Δξ which arise from sodium transport occur by either a single mechanism or by one which shares common features.  相似文献   

13.
Summary Hassell andVarley described a negative relationship between the Nicholsonianarea of discovery and parasitoid density that permits coexistence of two or more parasitoid species and yields stability. They ascribed the relationship to “mutual interference” among searching parasitoid adults, leading to a “decreased efficiency”. This matter has recently been studied in more detail byHassell and coworkers. Negative relationships can occur for several reasons. In the present paper it is shown that the negative relation occurs under certain assumptions about the way parasitoid eggs are distributed among hosts. Several “contagious” (or “clustered”) distributions were studied. Those assuming variation in host susceptibility or accessibility (negative binomial and added zeros distributions) yielded negative relations. Those assuming variation in parasitoid aggressiveness and fecundity (Neyman Type A distributions) yielded variable results depending on how the distributions of parasitoids per host and of eggs per parasitoid were combined. It was found that, when analyzing actual data, sampling fluctuations can introduce strong negative relations either with or without “contagion”. In all instances, the relation betweenarea of discovery and parasitoid density is affected by host density and is, in general, not linear. The foregoing findings raise serious questions about thearea of discovery concept. An alternative approach is suggested. The initial phase of this study was supported by National Institute of Health Grant S-Rol-AI0611, under Prof.C. B. Huffaker, Division of Biological Control, Department of Entomology, University of California, Berkeley. The study was completed under National Science Foundation Grant GB38271X. Paper no. 4705 of the Journal Series of the North Carolina Agricultural Experiment Station Raleigh.  相似文献   

14.
Two interesting results encountered in the literature concerning the Poisson and the negative binomial distributions are due to Moran (1952) and Patil & Seshadri (1964), respectively. Morans result provided a fundamental property of the Poisson distribution. Roughly speaking, he has shown that if Y, Z are independent, non-negative, integer-valued random variables with X = Y | Z then, under some mild restrictions, the conditional distribution of Y | X is binomial if and only if Y, Z are Poisson random variables. Motivated by Morans result Patil & Seshadri obtained a general characterization. A special case of this characterization suggests that, with conditions similar to those imposed by Moran, Y | X is negative hypergeometric if and only if Y, Z are negative binomials. In this paper we examine the results of Moran and Patil & Seshadri in the case where the conditional distribution of Y | X is truncated at an arbitrary point k – 1 (k = 1, 2, …). In fact we attempt to answer the question as to whether Morans property of the Poisson distribution, and subsequently Patil & Seshadris property of the negative binomial distribution, can be extended, in one form or another, to the case where Y | X is binomial truncated at k – 1 and negative hypergeometric truncated at k – 1 respectively.  相似文献   

15.
Summary We have devised a method whereby any mutagenized cloned DNA from Bacillus subtilis can be reinserted at the original site on the B. subtilis chromosome. The procedure depends on the accuracy and high frequency of homologous recombination between the B. subtilis chromosome and the DNA taken up by the cell. The method makes use of two drug resistance selection markers (the chloramphenicol resistance gene and the neomycin resistance gene) and a marker gene which functions as a catalyst. The utility of the method has been demonstrated using leuB and pro of B. subtilis as target gene and catalyst, respectively, and mutations such as leuB: : cat, leuB , and pro: : neo constructed in vitro on the cloned DNA fragments. Transformation in sequential steps as (leuB + pro+)(leuB: : cat pro +) (leuB pro: : neo)(leuB pro +) resulted in a leuB single mutant without affecting other regions of the B. subtilis chromosome (gene-directed mutagenesis). We also demonstrate that other single mutations such as metD and pro , as well as the double mutation leuB pro can be introduced by the same procedure. In principle, true isogenies with multiple mutations can be constructed by the method described in this paper. Furthermore, the procedure should be generally applicable to any organisms in which homologous recombination is proficient.  相似文献   

16.
The physico-chemical characteristics and possible formation mechanisms of negative air ions are considered. It was found that the products of oxygen and nitrogen negative ionization reduce ferricytochromec and nitroblue tetrazolium, and that these reactions were inhibited by superoxide dismutase. The interaction of negatively ionized oxygen with water led to hydrogen peroxide accumulation, which was inhibited by tetranitromethane or catalase. Nitrogen ionization under these conditions caused the formation of the hydrated electron e aq and the superoxide anion O 2 . The data obtained indicate that the biological activity of negative air ions may be dependent on superoxide. The generation of reactive oxygen ions in the gas phase and also at a gas/water interface is described. A scheme for superoxide production under oxygen and nitrogen ionization is proposed.  相似文献   

17.
Cells make many transitions from an old to a new phase of activity - between inactive and active states of an enzyme, or between phases of the cell cycle. If a cell is to survive, molecular prerequisites for functioning in the new phase should be available before a transition occurs. The cell’s survival is more likely if a regulatory network gates the transition, preventing its occurrence until the prerequisites are available. Suppose a specific conjunction of inputs is required for a network, from which a single output governs the transition. Then we suggest that cells are likely to use negative regulation - a gating network based on a logical disjunction of signals for the absence of prerequisites - rather than positive regulation - a logical conjunction of signals for their presence. That is, if a logical conjunction of n prerequisites A1 ANDA2 ANDANDAn is needed in the new phase, a negative regulatory network is likely to enforce the corresponding logical disjunction, NOT (NOTA1 ORNOTA2 ORORNOTAn). Five examples illustrate this conclusion. Arguments based on performance criteria support the hypothesis: negative regulation is more economical than positive regulation, because networks for computing OR can use fewer and simpler parts than those for computing AND. Negative regulation can increase reliability, because a mechanism that uses fewer, simpler parts is less likely to fail. And, a negative regulatory network can be more robust - less susceptible to errors resulting from noisy input.  相似文献   

18.
The process generating the negative binomial in the distribution pattern of eggs of the common cabbage butterfly, Pieris rapae crucivora, was investigated by releasing the female adults in a net house where cabbages were planted. The distribution of butterflies visited and laid an egg or more per plant followed thePoisson series under the uniform light condition, while that of eggs laid per visit conformed to the logarithmic distribution. From these results, it may be concluded that the negative binomial arises from compounding of thePoisson and the logarithmic distribution. The observed frequency of eggs found per plant fitted to the negative binomial with parameter thus computed theoretically. The change in the degree of aggregation with the increase of the parental density was considered in connection with the above results.  相似文献   

19.
A series of 3-(pyridin-2-yl-ethynyl)benzamide negative allosteric modulators of the metabotropic glutamate receptor 5 (mGluR5 NAMs) have been prepared. Starting from HTS hit 1 (IC50: 926 nM), potent mGluR5 NAMs showing excellent potencies (IC50s <50 nM) and good physicochemical profiles were prepared by monitoring LipE values. One compound 26 showed excellent mGluR5 binding (Ki: 21 nM) and antagonism (IC50: 8 nM), an excellent rat PK profile (CL: 12 mL/min/kg, %F: 85) and showed oral activity in a mouse 4-Plate Behavioral model of anxiety (MED: 30 mpk) and a mouse Stress Induced Hyperthermia model of anxiety (MED 17.8 mpk).  相似文献   

20.
Formulae are derived for the probability of obtaining negative estimates of heritability (h2) in full-sib analysis under the additive-dominance-epistasis model of gene action. Evaluation of the probabilities was undertaken for several combinations of sire/dam number, h2 and proportions of dominance and additive X additive epistatic variances, assuming two full-sibs per mating and that the dominance related epistasis is absent. In the light of the results, minimum sample sizes for obtaining admissible estimates from sire, dam components and their combination have been prescribed.  相似文献   

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