Structure-based protein design with deep learning

Since the first revelation of proteins functioning as macromolecular machines through their three dimensional structures, researchers have been intrigued by the marvelous ways the biochemical processes are carried out by proteins. The aspiration to understand protein structures has fueled extensive efforts across different scientific disciplines. In recent years, it has been demonstrated that proteins with new functionality or shapes can be designed via structure-based modeling methods, and the design strategies have combined all available information — but largely piece-by-piece — from sequence derived statistics to the detailed atomic-level modeling of chemical interactions. Despite the significant progress, incorporating data-derived approaches through the use of deep learning methods can be a game changer. In this review, we summarize current progress, compare the arc of developing the deep learning approaches with the conventional methods, and describe the motivation and concepts behind current strategies that may lead to potential future opportunities.     

Microbial carbonate production in a starved basin: The crenistria Limestone of the upper Viséan German Kulm facies

The crenistria Limestone is a set of three autochthonous massive limestone beds occurring with great lithological persistence in the Kulm Facies (cd III , upper Viséan) of the eastern Rheinisches Schiefergebirge. Microfacies analysis reveals mainly minipeloidal fabrics and homogeneous micrite. Uncrushed, sediment-filled conchs of goniatites represent loci of sheltered preservation of primary carbonate textures. Calcified radiolarians are abundant, forming between 20 and 80% of total rock volume. The alleged algal genus Rectangulina is common in the crenistria Limestone. It is reinterpreted to represent the faeces of goniatites. For the first time the presence of in situ preserved sponges is reported. They can be recognized as delicate networks of microsparitic needles embedded in peloidal fabrics. Hexactinellids with primary spicule arrangements can be found embedded in homogeneous micrite. The carbonate forming the limestone beds was produced microbially during decomposition of soft tissue of the radiolarians and sponges. During the cd III , anoxia in the bottom waters of the Kulm Basin persisted for long periods due to stable density stratification of the water column under humid climatic conditions. Oxic conditions in the bottom waters during formation of the limestone are indicated by bioturbation, the presence of sponges and the high Mn-contents of the carbonate. The latter derived from reduction of Mn-oxides during microbial carbonate formation.     

冷冻液温和季节对鼠尾过冷点的影响

为研究动物对寒冷的适应性,将鼠尾置于冷液浸冻,发现在一定条件下鼠尾组织可发生过冷现象。实验表明,鼠尾组织的过冷点和冷冻液温有关,同一季节冷冻液温越低过冷点越高;而不同季节相同冷冻条件下,冬季鼠尾组织的过冷点明显低于春季。 动物肢体组织的过冷特性是动物的抗寒冷特性,它和组织自身的物理化学性质有关。理沦证明,过冷度(△T)和表面张力(O)、摩尔质量(M),冰点(Ti)、密度(p)、摩尔凝固热(△H)及冰胚临界半径(rk)有关,其关系式为△T=26MTi/p△Hrk.     

核仁组成区蛋白在软组织肿瘤及瘤样病变中的表达与意义

应用胶银技术,对软组织肿瘤特别是纤维源性肿瘤核仁组成区蛋白进行了定量研究。在软组织一些恶性肿瘤中,以血管肉瘤、横纹肌肉瘤核仁组成区蛋白均值最高,并以此排列了它们的恶性度顺序。在纤维源性肿瘤中,纤维瘤、瘤样纤维组织增生、纤维肉瘤及其亚类核仁组成区蛋白均值有显著与高度显著性差异(P<0.05、P<0.001),其中随访的34例纤维肉瘤患者,具有高核仁组成区蛋白均值(≥5)与低核仁组成区蛋白均值(<5)的5年生存率分别是20％和53％(P<0.05)。因此,作者认为核仁组成区蛋白定量在判定软组织肿瘤的恶性度、鉴别其良恶性及预测患者预后中均有一定实用价值。     

基于主体功能区的长江经济带绿色发展评价与问题区域识别

长江经济带已成为我国推进绿色发展的重要阵地。基于主体功能区视角,构建以水系统为纽带的长江经济带绿色发展评价指标体系,采用综合加权法、空间自相关、耦合协调度模型等方法探究2018年长江经济带130个城市绿色发展及各子系统耦合协调水平的空间格局,并对绿色发展的问题区域进行分类识别。结果表明：(1)长江经济带绿色发展水平呈由下游、中游至上游递减趋势;各主体功能区绿色发展指数表现为优化开发区>限制开发区>重点开发区。(2)绿色发展各子系统耦合协调度值位于0.365—0.656之间,多处于濒临失调和勉强协调的临界区间,耦合协调水平整体偏低。(3)从长江经济带整体来看,长江中上游地区绝大部分城市绿色发展主要受资源利用和产业发展水平偏低,及由此带来的生态和生活问题限制,且长江中上游地区各省会或直辖市对区域内其他城市绿色发展带动能力不足。从主体功能区视角来看,优化开发区以生态问题为主,仅上海和嘉兴两市;重点开发区以生态和生产问题为主,集中于武汉都市圈和成渝双城经济圈内部;限制开发区以生产和生活问题为主,主要位于省际边界型城市地区。最后综合问题识别结果,分别对长江经济带各主要问题区域绿色发展...     

放牧对祁连山高寒典型草原土壤质量的影响

土壤质量是维持陆地生态系统稳定性与功能多样性的基础。放牧作为草地资源最广泛的利用方式之一,其对草地土壤质量的影响却缺乏量化标准,且两者之间的作用机理尚不明确。以祁连山高寒草原两个季节性牧场为研究对象,结合生态系统耦合与生态系统多功能性,探究了放牧对高寒草原土壤质量的影响与潜在机制。试验结果表明：基于最小数据集,不同放牧率下土壤质量指数差异显著(P<0.05),冬季牧场和春秋季牧场放牧率分别在2.45头月^-1 hm^-2和0.80头月^-1 hm^-2时土壤质量指数最高。土壤速效磷、有机碳、氮磷比和土壤pH是决定冬季牧场土壤质量的关键因子,而春秋季牧场中则是土壤有机碳、碳氮比和土壤pH;两个季节性牧场土壤质量指数与物种丰富度指数(P<0.05)和香浓维纳多样性指数(P<0.0001)呈显著正相关。高寒草原季节性牧场放牧地植物群落物种多样性与土壤因子耦合度在0.67—0.81之间,平均耦合度为0.74,属于中度协调;随着放牧率的增加,生态系统多功能性指数逐渐减低且与土壤质量指数变化趋势相似,...     

不健全资料的参数关联分析法

首先建立相关变量取值随时序变化的数学模型,而后,利用模型中能够反映变量几何形状的适宜参数,提出了参数关联度的概念．从而解决了观测值非一一对应、且不齐的相关变量关联分析问题．同时给出一种较高拟合精度的非等间隔序列的灰色建模方法．     

多元方差分析中的单一自由度独立比较

本文根据一元方差分析的单一自由度比较原理提出了多元方差分析中的单一自由度比较方法,以用于各种平衡试验设计中具多个变量的处理间多重比较．