一个仿真突触超微结构的三阶神经网络模型

神经系统内突触类型的多样性是与其机能的复杂性密切相关的.考虑到这一特性.本文用一个三阶神经网络模型仿真突触超微结构中的复合型连续性突触结构.作出了该模型的理论推导和分析.对由40个单元组成的网络系统作了计算机仿真、所得结果表明其存储容量可达680个图样.对其吸引盆也进行了仿真分析,对新模型与传统的Hebb学习律下的Hopfield模型进行了对比仿真.发现新模型具有比后者快得多的演化速率.     

Does predator interference cause alternative stable states in multispecies communities?

Whereas it is well known that simple ecological mechanisms may promote stability in simple species models, their consequences for stability and resilience in multispecies communities are largely unexplored. Here, we studied the effect of predator interference on the occurrence of alternative attractors and complex dynamics in randomly constructed multispecies predator-prey communities. We studied three types of interference: random interference (“asymmetric”), random interference but symmetrical between pairs of predators (“symmetric”), and interference among only the same species (“conspecific”). In all cases predator interference increased the average number of alternative attractors, whereas at the same time it reduced the emergence of oscillatory or chaotic dynamics. Our findings demonstrate a contrasting effect of predator interference on the stability of a community: on the one hand it reduces cycles and chaos in the dynamics, on the other hand predator interference increases the likelihood that communities may undergo critical transitions between multiple stable states.     

Noises-induced regime shifts and -enhanced stability under a model of lake approaching eutrophication

In this paper, we study the lake eutrophication by using a stochastic model that includes both input noise and recycling noise. The effects of the input noise (α), the recycling noise (D) and the cross-correlation between two noises (λ) in the model are discussed, respectively. Our results show: (i) the noise-induced ecological bistability (EB) expands in comparison with the deterministic case; (ii) noises still can induce EB when the recycling parameter r < 0.5; (iii) the noises can cause the regime shifts from the eutrophic state to the oligotrophic one (noise-induced oligotrophy); and (iv) the input noise can accelerate regime shifts from the oligotrophic state to the eutrophic one for the case of zero or small cross-correlation. Moreover, for the case of higher cross-correlation intensity, the mean first passage time (MFPT) as a function of α exhibits a maximum, which identifies the input noise-enhanced stability (NES) of the oligotrophic state. Finally, for whatever value of cross-correlation intensity, the theoretical results show that the recycling noise can accelerate regime shifts from the oligotrophic state to the eutrophic one.     

Shallow lake restoration by nutrient loading reduction—some recent findings and challenges ahead

Shallow lakes respond to nutrient loading reductions. Major findings in a recent multi-lake comparison of data from lakes with long time series revealed: that a new state of equilibrium was typically reached for phosphorus (P) after 10–15 years and for nitrogen (N) after <5–10 years; that the in-lake Total N:Total P and inorganic N:P ratios increased; that the phytoplankton and fish biomass often decreased; that the percentage of piscivores often increased as did the zooplankton:phytoplankton biomass ratio, the contribution of Daphnia to zooplankton biomass, and cladoceran size. This indicates that enhanced resource and predator control often interact during recovery from eutrophication. So far, focus has been directed at reducing external loading of P. However, one experimental study and cross-system analyses of data from many lakes in north temperate lakes indicate that nitrogen may play a more significant role for abundance and species richness of submerged plants than usually anticipated when total phosphorus is moderate high. According to the alternative states hypothesis we should expect ecological resistance to nutrient loading reduction and P hysteresis. We present results suggesting that the two alternative states are less stable than originally anticipated. How global warming affects the water clarity of shallow lakes is debatable. We suggest that water clarity often will decrease due to either enhanced growth of phytoplankton or, if submerged macrophytes are stimulated, by reduced capacity of these plants to maintain clear-water conditions. The latter is supported by a cross-system comparison of lakes in Florida and Denmark. The proportion of small fish might increase and we might see higher aggregation of fish within the vegetation (leading to loss of zooplankton refuges), more annual fish cohorts, more omnivorous feeding by fish and less specialist piscivory. Moreover, lakes may have prolonged growth seasons with a higher risk of long-lasting algal blooms and at places dense floating plant communities. The effects of global warming need to be taken into consideration by lake managers when setting future targets for critical loading, as these may well have to be adjusted in the future. Finally, we highlight some of the future challenges we see in lake restoration research.     

Integrating cell-cycle progression, drug penetration and energy metabolism to identify improved cancer therapeutic strategies

The effectiveness of chemotherapeutic drugs in tumors is reduced by multiple effects including drug diffusion and variable susceptibility of local cell populations. We hypothesized that quantifying the interactions between drugs and tumor microenvironments could be used to identify more effective anti-cancer strategies. To test this hypothesis we created a mathematical model that integrated intracellular metabolism, nutrient and drug diffusion, cell-cycle progression, cellular drug effects, and drug pharmacokinetics. To our knowledge, this is the first model that combines these elements and has coupled them to experimentally derived parameters. Drug cytotoxicity was assumed to be cell-cycle phase specific, and progression through the cell cycle was assumed to be dependent on ATP generation. The model consisted of a coupled set of nonlinear partial differential, ordinary differential and algebraic equations with an outer free boundary, which was solved using orthogonal collocation on a moving grid of finite elements. Model simulations showed the existence of an optimum drug diffusion coefficient: a low diffusivity prevents effective penetration before the drug is cleared from the blood and a high diffusivity limits drug retention. This result suggests that increasing the molecular weight of the anti-cancer drug paclitaxel from 854 to approximately 20,000 by nano-particle conjugation would improve its efficacy. The simulations also showed that fast growing tumors are less responsive to therapy than are slower tumors with more quiescent cells, demonstrating the competing effects of regrowth and cytotoxicity. The therapeutic implications of the simulation results are that (1) monolayer cultures are inadequate for accurately determining therapeutic effects in vitro, (2) decreasing the diffusivity of paclitaxel could increase its efficacy, and (3) measuring the proliferation fraction in tumors could enhance the prediction of therapeutic efficacy.     

Conformational transitions and aggregation in poly(dA)-poly(dT) system induced by Na+ and Mg2+ ions

Effects of Mg²⁺ ions on thermally induced conformational transitions in the synthetic poly(dA)·poly(dT) and poly(dA)·2poly(dT) were studied in the buffered solutions (pH 6.9), containing 0.1 or 1 M NaCl at polynucleotide concentration of 0.1–0.3 mM (in nucleic bases). The experiments consist of measurements of the UV absorption and intensity of conventional visible static light scattering. The diagram of conformational transitions in the poly(dA)–poly(dT)–Mg²⁺ system was constructed on a basis of experimental data obtained. Anomalously strong light scattering, like critical opalescence, has been revealed at 0.1 M NaCl and [Mg²⁺]≥20 mM in the melting range of both polynucleotides, which eventually disappeared after the completion of polymer strands separation. The effect presumably is caused by a fluctuation process of polymer strands complexing which arises at a certain concentration of Mg²⁺ ions.     

Marine regime shifts: drivers and impacts on ecosystems services

Marine ecosystems can experience regime shifts, in which they shift from being organized around one set of mutually reinforcing structures and processes to another. Anthropogenic global change has broadly increased a wide variety of processes that can drive regime shifts. To assess the vulnerability of marine ecosystems to such shifts and their potential consequences, we reviewed the scientific literature for 13 types of marine regime shifts and used networks to conduct an analysis of co-occurrence of drivers and ecosystem service impacts. We found that regime shifts are caused by multiple drivers and have multiple consequences that co-occur in a non-random pattern. Drivers related to food production, climate change and coastal development are the most common co-occurring causes of regime shifts, while cultural services, biodiversity and primary production are the most common cluster of ecosystem services affected. These clusters prioritize sets of drivers for management and highlight the need for coordinated actions across multiple drivers and scales to reduce the risk of marine regime shifts. Managerial strategies are likely to fail if they only address well-understood or data-rich variables, and international cooperation and polycentric institutions will be critical to implement and coordinate action across the scales at which different drivers operate. By better understanding these underlying patterns, we hope to inform the development of managerial strategies to reduce the risk of high-impact marine regime shifts, especially for areas of the world where data are not available or monitoring programmes are not in place.     

Contrasting impacts of invasive engineers on freshwater ecosystems: an experiment and meta-analysis

Invasion by common carp (Cyprinus carpio) and red swamp crayfish (Procambarus clarkii) in shallow lakes have been followed by stable-state changes from a macrophyte-dominated clear water state to a phytoplankton-dominated turbid water state. Both invasive carp and crayfish are, therefore, possible drivers for catastrophic regime shifts. Despite these two species having been introduced into ecosystems world-wide, their relative significance on regime shifts remains largely unexplored. We compared the ecological impacts of carp and crayfish on submerged macrophytes, water quality, phytoplankton, nutrient dynamics, zooplankton and benthic macroinvertebrates by combining an enclosure experiment and a meta-analysis. The experiment was designed to examine how water quality and biological variables responded to increasing carp or crayfish biomass. We found that even at a low biomass, carp had large and positive impacts on suspended solids, phytoplankton and nutrients and negative impacts on benthic macroinvertebrates. In contrast, crayfish had a strong negative impact on submerged macrophytes. The impacts of crayfish on macrophytes were significantly greater than those of carp. The meta-analysis showed that both carp and crayfish have significant effects on submerged macrophytes, phytoplankton, nutrient dynamics and benthic macroinvertebrates, while zooplankton are affected by carp but not crayfish. It also indicated that crayfish have significantly greater impacts on macrophytes relative to carp. Overall, the meta-analysis largely supported the results of the experiment. Taken as a whole, our results show that both carp and crayfish have profound effects on community composition and ecosystem processes through combined consequences of bioturbation, excretion, consumption and non-consumptive destruction. However, key variables (e.g. macrophytes) relating to stable-state changes responded differently to increasing carp or crayfish biomass, indicating that they have differential ecosystem impacts.     

长江亚热带浅水湖群藻类浊度与非藻类浊度的变异规律

浊度的上升是湖泊富营养化过程中沉水植物消失、由草向藻发生稳态转换的根本原因。研究利用长江中下游浅水湖群区域数据对藻类浊度（Turb_Alg）和非藻类浊度（Turb_NonAlg）及其对总浊度（Turb_Tot）的贡献率（Turb_Alg%,Turb_NonAlg%）进行了推算。结果显示,在该区域非藻类浊度绝对值及其贡献率均普遍高于藻类浊度;Turb_Alg主要受限于总磷（TP）,而Turb_NonAlg受水深（Z_M）、TP和沉水植物等多重因素的影响。Turb_Alg和Turb_NonAlg呈现出随着TP浓度的升高而持续上升的趋势,表明尽管稳态转换存在特定的阈值,但整个富营养化过程中均需加强对营养物浓度的控制。     

Alternative (un)stable states in a stochastic predator–prey model

Stochastic models sometimes behave qualitatively differently from their deterministic analogues. We explore the implications of this in ecosystems that shift suddenly from one state to another. This phenomenon is usually studied through deterministic models with multiple stable equilibria under a single set of conditions, with stability defined through linear stability analysis. However, in stochastic systems, some unstable states can trap stochastic dynamics for long intervals, essentially masquerading as additional stable states. Using a predator–prey model, we demonstrate that this effect is sufficient to make a stochastic system with one stable state exhibit the same characteristics as an analogous system with alternative stable states. Although this result is surprising with respect to how stability is defined by standard analyses, we show that it is well-anticipated by an alternative approach based on the system's “quasi-potential.” Broadly, understanding the risk of sudden state shifts will require a more holistic understanding of stability in stochastic systems.     

Loss of putative tumor suppressor EI24/PIG8 confers resistance to etoposide

Expression of p53-target gene EI24/PIG8 is lost in invasive breast cancers, suggesting that EI24/PIG8 is a tumor suppressor that prevents tumor spreading, and partially mediates p53-attributed tumor suppressor activity. EI24/PIG8 also has pro-apoptotic activity indicating that loss of EI24/PIG8 may modulate sensitivity to chemotherapy. Here it is demonstrated that suppression of EI24/PIG8 in fibroblasts and breast cancer cells significantly inhibits the apoptotic response to etoposide treatment. These findings suggest that loss of EI24/PIG8 contributes significantly to resistance of cells to chemotherapeutic agents that function through p53, and identify the EI24/PIG8 status as a potentially new prognostic marker of chemotherapy responsiveness.     

Resilience and stability of a pelagic marine ecosystem

The accelerating loss of biodiversity and ecosystem services worldwide has accentuated a long-standing debate on the role of diversity in stabilizing ecological communities and has given rise to a field of research on biodiversity and ecosystem functioning (BEF). Although broad consensus has been reached regarding the positive BEF relationship, a number of important challenges remain unanswered. These primarily concern the underlying mechanisms by which diversity increases resilience and community stability, particularly the relative importance of statistical averaging and functional complementarity. Our understanding of these mechanisms relies heavily on theoretical and experimental studies, yet the degree to which theory adequately explains the dynamics and stability of natural ecosystems is largely unknown, especially in marine ecosystems. Using modelling and a unique 60-year dataset covering multiple trophic levels, we show that the pronounced multi-decadal variability of the Southern California Current System (SCCS) does not represent fundamental changes in ecosystem functioning, but a linear response to key environmental drivers channelled through bottom-up and physical control. Furthermore, we show strong temporal asynchrony between key species or functional groups within multiple trophic levels caused by opposite responses to these drivers. We argue that functional complementarity is the primary mechanism reducing community variability and promoting resilience and stability in the SCCS.     

培美曲塞治疗复发性卵巢癌疗效观察及对糖类抗原125、人肿瘤坏死因子α的影响研究

目的:观察培美曲塞治疗复发性卵巢癌疗效及对糖类抗原125、人肿瘤坏死因子α的影响。方法:回顾性分析2014年3月至2017年6月我院收住院治疗的92例复发性卵巢癌患者的临床资料。根据化疗方式不同分为观察组(培美曲塞)和对照组(紫杉醇联合伊立替康)。统计分析两组患者近期疗效、不良反应、化疗前后血清肿瘤标志物水平。结果:观察组缓解率为60.9%(28/46),明显高于对照组32.6%(15/46),差异具有统计学意义(P0.05)。观察组骨髓抑制发生率为45.7%(21/46),明显低于对照组67.4%(31/46),差异具有统计学意义(P0.05);两组胃肠道反应、脱发、肾功能损害、肝功能损害等不良反应发生率无明显差异(P0.05)。观察组治疗后CA125、TNF-α水平均明显低于对照组,差异具有统计学意义(P0.05)。结论:培美曲塞治疗复发性卵巢癌疗效可靠,安全性高,且对降低患者CA125、TNF-α水平具有重要作用,值得临床借鉴使用。     

熊果酸在肿瘤治疗中的研究进展

熊果酸(ursolic acid)是广泛存在于自然界植物中的一种五环三萜类化合物,具有广泛的生物学活性,主要经肝脏代谢。传统临床治疗中熊果酸多用于抗炎、抗病毒、调节免疫功能以及保肝治疗等。近年来的研究表明,在体外和体内实验中,熊果酸能够对不同肿瘤细胞产生杀伤作用,抑制恶性肿瘤组织的生长,具有广谱的抗肿瘤活性。此外,熊果酸联合放化疗能够提高肿瘤细胞对治疗的敏感性,产生辅助增强放化疗疗效的作用,并且在放疗中可保护受照射机体的正常组织,促进免疫机能的恢复。熊果酸的抗肿瘤作用机制与下调促肿瘤生长、侵袭和转移相关基因的水平,增强凋亡基因的表达有关,并且能够通过调节多种细胞信号转导通路,杀灭肿瘤细胞,延缓肿瘤组织生长。同时,熊果酸可影响肿瘤细胞周期的分布,导致细胞的G1/S期阻滞,从而抑制肿瘤细胞的有丝分裂,诱导细胞凋亡。因此,熊果酸是一种极具潜力的天然抗肿瘤药物。本文对熊果酸在肿瘤治疗中的研究结果进行整合,阐述了熊果酸的抗肿瘤分子机制及其疗效,为熊果酸今后在临床中的进一步应用提供指导思路。     

A Microenvironment Based Model of Antimitotic Therapy of Gompertzian Tumor Growth

A model of tumor growth, based on two-compartment cell population dynamics, and an overall Gompertzian growth has been previously developed. The main feature of the model is an inter-compartmental transfer function that describes the net exchange between proliferating (P) and quiescent (Q) cells and yields Gompertzian growth for tumor cell population N = P + Q. Model parameters provide for cell reproduction and cell death. This model is further developed here and modified to simulate antimitotic therapy. Therapy decreases the reproduction-rate constant and increases the death-rate constant of proliferating cells with no direct effect on quiescent cells. The model results in a system of two ODE equations (in N and P/N) that has an analytical solution. Net tumor growth depends on support from the microenvironment. Indirectly, this is manifested in the transfer function, which depends on the proliferation ratio, P/N. Antimitotic therapy will change P/N, and the tumor responds by slowing the transfer rate from P to Q. While the cellular effects of therapy are modeled as dependent only on antimitotic activity of the drug, the tumor response also depends on the tumor age and any previous therapies—after therapy, it is not the same tumor. The strength of therapy is simulated by the parameter λ, which is the ratio of therapy induced net proliferation rate constant versus the original. A pharmacodynamic factor inversely proportional to tumor size is implemented. Various chemotherapy regimens are simulated and the outcomes of therapy administered at different time points in the life history of the tumor are explored. Our analysis shows: (1) for a constant total dose administered, a decreasing dose schedule is marginally superior to an increasing or constant scheme, with more pronounced benefit for faster growing tumors, (2) the minimum dose to stop tumor growth is age dependent, and (3) a dose-dense schedule is favored. Faster growing tumors respond better to dose density.