Aminoadamantanes containing monoterpene-derived fragments as potent tyrosyl-DNA phosphodiesterase 1 inhibitors

The ability of a number of nitrogen-containing compounds that simultaneously carry the adamantane and monoterpene moieties to inhibit Tdp1, an important enzyme of the DNA repair system, is studied. Inhibition of this enzyme has the potential to overcome chemotherapeutic resistance of some tumor types. Compound (+)-3c synthesized from 1-aminoadamantane and (+)-myrtenal, and compound 4a produced from 2-aminoadamantane and citronellal were found to be most potent as they inhibited Tdp1 with IC₅₀ values of 6 and 3.5 µM, respectively. These compounds proved to have low cytotoxicity in colon HCT-116 and lung A-549 human tumor cell lines (CC₅₀ > 50 µM). It was demonstrated that compound 4a at 10 µM enhanced cytotoxicity of topotecan, a topoisomerase 1 poison in clinical use, against HCT-116 more than fivefold and to a lesser extent of 1.5 increase in potency for A-549.     

气候变化下中国八种梧桐属树种潜在适生区模拟

中国梧桐属（Firmiana）在世界梧桐属中占比较大，且除梧桐外其余种均为中国特有且分布范围狭窄的植物种，灭绝风险大，研究气候变化对中国梧桐属树种的影响对于维护生物多样性具有重要的意义。结合多时期第六次国际气候耦合模式比较计划（CMIP6）气候变量数据和中国八种梧桐属树种的分布数据，基于R语言kuenm程序包优化的最大熵（Maxent）模型模拟分析中国八种梧桐属树种在多尺度下的潜在适生区，得出梧桐属最适宜的模拟尺度、潜在适生区的面积变化和迁移方向、梧桐属多样性保护关键区域及保护空缺。结果表明：（1）梧桐属最适宜的模拟尺度为亚洲；（2） Maxent模型的接收者操作特征曲线下面积（AUC）值均大于0.9，表明模型对梧桐属潜在适生区预测结果具有较高准确度；（3）气候变化影响下除云南梧桐（Firmiana major）外其它树种的潜在适生区都将在未来有所扩大；（4）中国八种梧桐属树种潜在适生区迁移方向主要为东西向，南北向大跨度迁移较少，纬度变化不大；（5）丹霞梧桐（Firmiana danxiaensis）的稳定潜在适生区最小；（6）中国梧桐属多样性保护关键区域主要分布于广西壮族自治区及云南、广东、海南等省区；（7）中国梧桐属多样性保护空缺区域主要分布于广西壮族自治区中部及海南省北部；（8）梧桐属多样性保护关键区域正在为人造地表所侵蚀。研究分析气候变化对中国八种梧桐属树种的影响及其潜在适生区变化、中国梧桐属多样性保护状态，可为中国梧桐属建立多样性保护廊道提供相关建议，为制定多样性保护规划及相应措施提供参考。     

Can cost–benefit analysis explain fish distribution patterns?

This review describes some recent theoretical and empirical research into the way fish respond to spatial heterogeneity in their environment, and particularly to patchily distributed resources. The ways in which the need to acquire food interacts with other important requirements such as thermoregulation and predator avoidance to determine space use are considered, as are interactions with other members of the same species, viewed both as shoaling companions and as competitors. Recent developments in ideal free theory are discussed and the extent to which this formulation can explain how fish distribute themselves among feeding patches is examined. The implications of overtly aggressive interactions, in the form of dominance hierarchies and territorial systems, for distribution patterns in the laboratory and in the field are also reviewed. Finally the extent to which cost–benefit analysis can help to explain fish distribution patterns and the relative importance of behavioural processes compared to other determinants of the distribution of fish are considered.     

Estimating the ability of plants to plastically track temperature‐mediated shifts in the spring phenological optimum

One consequence of rising spring temperatures is that the optimum timing of key life‐history events may advance. Where this is the case, a population's fate may depend on the degree to which it is able to track a change in the optimum timing either via plasticity or via adaptation. Estimating the effect that temperature change will have on optimum timing using standard approaches is logistically challenging, with the result that very few estimates of this important parameter exist. Here we adopt an alternative statistical method that substitutes space for time to estimate the temperature sensitivity of the optimum timing of 22 plant species based on >200 000 spatiotemporal phenological observations from across the United Kingdom. We find that first leafing and flowering dates are sensitive to forcing (spring) temperatures, with optimum timing advancing by an average of 3 days °C^?1 and plastic responses to forcing between ?3 and ?8 days °C^?1. Chilling (autumn/winter) temperatures and photoperiod tend to be important cues for species with early and late phenology, respectively. For most species, we find that plasticity is adaptive, and for seven species, plasticity is sufficient to track geographic variation in the optimum phenology. For four species, we find that plasticity is significantly steeper than the optimum slope that we estimate between forcing temperature and phenology, and we examine possible explanations for this countergradient pattern, including local adaptation.     

Computing the selection gradient and evolutionary response of an infinite-dimensional trait

 Following the results developed in a previous paper, an equation describing the evolutionary response to selection is extended from finite- to infinite-dimensional traits. The selection gradient and evolutionary response are then computed for a large class of infinite-dimensional traits of broad biological interest. In this framework, traits are modeled as Gaussian processes, and reproducing kernel Hilbert spaces constitute a primary tool. Received 12 September 1996     

Cartography and Clandestinité in Leïla Sebbar’s Shérazade: 17 ans, brune, frisée, les yeux verts

In this paper, I read Leïla Sebbar’s staging in her novel Shérazade: 17 ans, brune, frisée, les yeux verts of the resistance by children of North African and other immigrants in the early 1980s to the French state’s cartographic modes and documents of control. The paper will consider the many uses to which the map was put by the French state in its colonization of North Africa and particularly Algeria, and later in its attempts to control the banlieues its policies of citizenship and cartographic control yielded on the margins of Paris. In this context, I will explore the ways in which the novel’s characters, living clandestinely in a squatt, simultaneously resist, put to use, and even supercede state documents of control as they disrupt everyday life and conduct heists across the city of Paris. The paper will explore unofficial cartographies of Paris, from those afforded by the radios libres and alternative publications such as Libération and Sans Frontièrez, to oral and almost proverbial networks of knowledge criss-crossing the city of Paris, while also tracing the uses to which supplemental cartographic sketches and counterfeit identity cards are put in the pages of the novel. The paper will be in dialogue with theoretical and critical formulations of space, cartography, and state control put forward by Michel de Certeau, Henri Lefebvre, Michel Foucault, and Tom Conley. The paper will conclude with a consideration of the means and limits of resistance by the novel’s characters in the context of this body of theory and criticism.     

Nearest Neighbours: Estimators for Heterogeneity

Papadakis' method is shown to be an example of an estimation procedure for a heterogeneity function localized in a reproducing kernel Hilbert space. Within this framework some current models for the evaluation of field trials are discussed.