线性双滞量NDDE振动性的代数判据

本文给出一阶双滞量NDDE对所有参数振动与非振动的充要条件，这些条件用系统诸参数的若干代数式表达，方便于应用验证．     

Understanding how biodiversity unfolds through time under neutral theory

Theoretical predictions for biodiversity patterns are typically derived under the assumption that ecological systems have reached a dynamic equilibrium. Yet, there is increasing evidence that various aspects of ecological systems, including (but not limited to) species richness, are not at equilibrium. Here, we use simulations to analyse how biodiversity patterns unfold through time. In particular, we focus on the relative time required for various biodiversity patterns (macroecological or phylogenetic) to reach equilibrium. We simulate spatially explicit metacommunities according to the Neutral Theory of Biodiversity (NTB) under three modes of speciation, which differ in how evenly a parent species is split between its two daughter species. We find that species richness stabilizes first, followed by species area relationships (SAR) and finally species abundance distributions (SAD). The difference in timing of equilibrium between these different macroecological patterns is the largest when the split of individuals between sibling species at speciation is the most uneven. Phylogenetic patterns of biodiversity take even longer to stabilize (tens to hundreds of times longer than species richness) so that equilibrium predictions from neutral theory for these patterns are unlikely to be relevant. Our results suggest that it may be unwise to assume that biodiversity patterns are at equilibrium and provide a first step in studying how these patterns unfold through time.     

Molecular Weight of Human Brain Neutral Sphingomyelinase Determined In Situ by the Radiation Inactivation Method

The radiation inactivation method was used to determine the molecular weight of membrane-bound neutral sphingomyelinase from normal human brain. Inactivation curves showed a molecular mass of 167,000 +/- 32,000. Molecular weights of two control enzymes, beta-N-acetylglucosaminidase and nonspecific beta-glucosidase, determined by the same procedure, were consistent with previous reports.     

Compositional patterns in vertebrate genomes: Conservation and change in evolution

Summary The evolution of vertebrate genomes can be investigated by analyzing their regional compositional patterns, namely the compositional distributions of large DNA fragments (in the 30–100-kb size range), of coding sequences, and of their different codon positions. This approach has shown the existence of two evolutionary modes. In the conservative mode, compositional patterns are maintained over long times (many million years), in spite of the accumulation of enormous numbers of base substitutions. In the transitional, or shifting, mode, compositional patterns change into new ones over much shorter times.The conservation of compositional patterns, which has been investigated in mammalian genomes, appears to be due in part to some measure of compositional conservation in the base substitution process, and in part to negative selection acting at regional (isochore) levels in the genome and eliminating deviations from a narrow range of values, presumably corresponding to optimal functional properties. On the other hand, shifts of compositional patterns, such as those that occurred between cold-blooded and warm-blooded vertebrates, appear to be due essentially to both negative and positive selection again operating at the isochore level, largely under the influence of changes in environmental conditions, and possibly taking advantage of mutational biases in the replication/repair enzymes and/or in the enzyme make-up of nucleotide precursor pools. Other events (like translocations and changes in chromosomal structure) also play a role in the transitional mode of genome evolution.The present findings (1) indicate that isochores, which correspond to the DNA segments of individual or contiguous chromatin domains, represent selection units in the vertebrate genome; and (2) shed new light on the selectionist-neutralist controversy.This work was presented at the EMBO Workshop on Evolution (Cambridge, UK, 4–6 July 1988) and at the 16th International Congress of Genetics (Toronto, Canada, 20–27 August 1988)     

Influence of follower load application on moment-rotation parameters and intradiscal pressure in the cervical spine

The objective of this study was to implement a follower load (FL) device within a robotic (universal force-moment sensor) testing system and utilize the system to explore the effect of FL on multi-segment cervical spine moment-rotation parameters and intradiscal pressure (IDP) at C45 and C56. Twelve fresh-frozen human cervical specimens (C3-C7) were biomechanically tested in a robotic testing system to a pure moment target of 2.0 Nm for flexion and extension (FE) with no compression and with 100 N of FL. Application of FL was accomplished by loading the specimens with bilateral cables passing through cable guides inserted into the vertebral bodies and attached to load controlled linear actuators. FL significantly increased neutral zone (NZ) stiffness and NZ width but resulted in no change in the range of motion (ROM) or elastic zone stiffness. C45 and C56 IDP measured in the neutral position were significantly increased with application of FL. The change in IDP with increasing flexion rotation was not significantly affected by the application of FL, whereas the change in IDP with increasing extension rotation was significantly reduced by the application of FL. Application of FL did not appear to affect the specimen’s quantity of motion (ROM) but did affect the quality (the shape of the curve). Regarding IDP, the effects of adding FL compression approximates the effect of the patient going from supine to a seated position (FL compression increased the IDP in the neutral position). The change in IDP with increasing flexion rotation was not affected by the application of FL, but the change in IDP with increasing extension rotation was, however, significantly reduced by the application of FL.     

Angiotensin and bradykinin metabolism by peptidases identified in cultured human skeletal muscle myocytes and fibroblasts

Angiotensin (ANG) and kinin metabolizing enzymes, angiotensin-converting enzyme (ACE; EC 3.4.15.1), neutral endopeptidase-24.11 (NEP-24.11; EC 3.4.24.11), and aminopeptidase M (AmM; EC 3.4.11.2), have recently been identified in a purified skeletal muscle glycoprotein fraction. We have analyzed the cellular localization of these enzymes. In cultured human skeletal muscle adult myoblasts, myotubes, and fibroblasts, kinins and angiotensins were metabolized by NEP-24.11 and AmM but not by ACE. NEP-24.11 degraded ANG II, ANG III, and bradykinin (BK) and converted ANG I to the active metabolite ANG(1–7). ANG III was converted to the novel ANG IV metabolite [des-Arg¹]ANG III by AmM. These data suggest that, due to their abundance in the body, skeletal muscle myocytes and fibroblasts may play a major role in modulation of the systemic and local effects of angiotensins and kinins. This role could be particularly important in individuals receiving treatment with ACE inhibitors.     

A theoretical method for evaluating the relative importance of positive selection and neutral drift from observed base changes

To evaluate the relative importance of positive selection and neutral drift from the nucleotide base changes observed in the homologous alignment of genes, a theoretical equation of base changes is formulated by including both the influence of selection and the base substitutions due to mutations. Under the assumption that the average rate of base substitutions estimated from synonymous changes is the ``true' mutation rate applicable at all positions, this method is applied to the vertebrate globin gene family, and evaluates the departures of base change rates from the ``true' mutation rate at the first and second codon positions as a consequence of preferential selection for the conservation of important function. In addition to the strong effect of selection on the amino acid residues in the internal region mostly common to myoglobin and hemoglobin chains, the distinctive directions of selective parameter values are seen at sites on the globin surface, distinguishing the subunit contact residues of hemoglobins from the polar residues on the surface of myoglobins. Moreover, this effect of selection distinguishing between the myoglobin and hemoglobin chain genes becomes weaker in cold-blooded vertebrates, especially in fish, strongly suggesting the possibility that the clear distinction between these globins is a result of selection out of the changes regarded as neutral ones in an ancestor of vertebrates. Thus, the present method may also serve to investigate the homology of many other proteins from the aspect of molecular evolution, mainly focusing on the evolution of their biological functions. Received: 2 January 1996 / Accepted: 20 February 1997     

Neutral red (NR) assay for cell viability and xenobiotic-induced cytotoxicity in primary cultures of human and rat hepatocytes

Neutral red (NR) in medium was absorbed and concentrated in lysosomes of cultured rat and human hepatocytes. NR uptake increased with the time of incubation and reached a plateau in 2 hr. Uptake was proportional to the concentration of the NR solution and the numbers of viable liver cells. Prolonged culture of hepatocytes increased the numbers of lysosomes, and thus, the dye accumulation. The NR can be extracted from lysosomes for quantitative measurement of hepatocyte viability and cytotoxicity of xenobiotics. With this assay, several serum-free media (e.g., Waymouth's, MEM, LHC-8, etc.) were compared for the maintenance of viable hepatocytes in vitro. Interestingly, LHC-8 medium, which is used to grow human bronchial epithelial cells, best preserved viable rat hepatocytes. The cytotoxic effects of dimethylnitrosamine (DMN) and aflatoxin B₁ (AFB₁) were examined by NR assay on rat and human hepatocyte cultures and were found to be dependent on dose and time of the exposures. NR₅₀ was 20 mM for DMN and 0.072 µM for AFB₁ in rat hepatocytes with 24 hr of exposures and reduced to 12.5 mM for DMN and 0.053 µ uM for AFB₁ with 48 fr exposures. Human hepatocytes were more resistant to the toxicity of both chemicals; NR₅₀ values were 100 mM DMN and 1.8 µM AFB₁ respectively, for 24 hr treatments. Compared with lactate dehydrogenase (LDH) leakage test, the NR assay was simpler and more sensitive in determining the viability and cytotoxicity of xenobiotics in primary cultures of hepatocytes.Abbreviations NR Neutral Red - MEM Eagle's Minimum Essential Medium - DMN dimethylnitrosamine - AFB₁ aflatoxin B₁ - LDH lactate dehydrogenase - HBSS Hanks balanced salt solution; - EDTA ethylene bis (oxyethylenenitrilo)-tetraacetic acid - L-15 Leibovitz's 15 - NADH B-nicotinamide adenine dinu - FBS fetal bovine serum - IA immediate autopsy Contribution No. 2816 from Laboratory of Genotoxicology.     

Localized or delocalized protons in photophosphorylation? On the accessibility of the thylakoid lumen for ions and buffers

The deposition of protons inside thylakoids after flash excitation was measured photometrically with neutral red as pH indicator. In continuation of previous work (Junge, W., Ausländer, W., McGeer, A. and Runge, T. (1979) Biochim. Biophys. Acta 546, 121–141), we studied the influence of salts on neutral red binding and on the pK of the heterogeneous protonation-deprotonation of inside-bound neutral red as a function of salts. With freeze-thawed (cryoprotective dimethyl sulphoxide) or aged chloroplasts, we observed that the heterogeneous pK of inside-bound neutral red was salt dependent in a way which suggested that neutral red was bound close to the plane of negative fixed charges and that the adjacent inner aqueous phase could accommodate an extended ionic double layer. This, together with the known extremely rapid proton exchange between surface layer and adjacent bulk phase, led us to conclude that inside-deposited protons rapidly reached an aqueous inner bulk phase. This conclusion was corroborated by the observation that extremely hydrophilic buffers like phosphate quenched the transient internal acidification independent of whether proton deposition was due to water oxidation or to plastohydroquinone oxidation. Very different behaviour was observed for freshly prepared chloroplasts with broken outer envelope. Here, inside-bound neutral red was seemingly unaffected by salts and hydrophilic buffers failed to quench the internal acidification. The electrical conductivity and proton permeability of the thylakoid membrane, on the other hand, were as usual. We attributed the seeming inaccessibility of the internal phase to the failure to accommodate a sufficiently extended ionic cloud between the tightly appressed membranes. In such material we observed hindered lateral mobility of protons at the outer side of the thylakoid membrane. This was tentatively attributed to multiple binding-debinding at buffering groups. The consequences for the chemiosmotic theory are: There is one type of damaged chloroplast material, which is competent in photophosphorylation and where protons are deposited into an internal aqueous bulk phase in the orthodox sense. In more intact material, however, the internal space lacks the characteristic properties of an aqueous bulk phase and there is evidence for lateral diffusion limitation for protons. Here, the thermodynamics of photophosphorylation may be inadequately described by the proton-motive force between two aqueous phases which are each isopotential.     

Evolution of the amino acid substitution in the mammalian myoglobin gene

Summary Multivariate statistical analyses were applied to 16 physical and chemical properties of amino acids. Four of these properties; volume, polarity, isoelectric point (charge), and hydrophobicity were found to explain adequately 96% of the total variance of amino acid attributes. Using these four quantitative measures of amino acid properties, a structural discriminate function in the form of a weighted difference sum of squares equation was developed. The discriminate function is weighted by the location of each particular residue within a given tertiary structure and yields a numerical discriminate or difference value for the replacement of these residues by different amino acids. This resulting discriminate value represents an expression of the perturbation in the local positional environment of a protein when an amino acid substitution occurs. With the use of this structural discriminate function, a residue by residue comparison of the known mammalian myoglobin sequences was carried out in an attempt to elucidate the positions of possible deviations from the known tertiary structure of sperm whale myoglobin. Only 11 of the 153 residue positions in myoglobin demonstrated possible structural deviations. From this analysis, indices of difference were calculated for all amino acid exchanges between the various myoglobins. All comparisons yielded indices of difference that were considerably lower than would be expected if mutations had been fixed at random, even if the organization of the genetic code is taken into consideration. On the basis of these results, it is inferred that some form of selection has acted in the evolution of mammalian myoglobins to favor amino acid substitutions that are compatible with the retention of the original conformation of the protein.