Bias-free separation of internal and overall motion of biomolecules

Collective internal motions are known to be important for the function of biological macromolecules. It has been discussed in the past whether the application of superimposing algorithms to remove the overall motion from a structural ensemble introduces artificial correlations between distant atoms. Here we present a new method to eliminate residual rotation and translation from cartesian modes derived from a normal mode analysis or from a principal component analysis. Bias-free separation is based on the idea that the addition of modes of pure rotation/translation can compensate the residual overall motion. Removal of overall motion must reduce the "total amount of motion" (TAM) in the mode. Our algorithm allows to back-calculate revised covariance matrices. The approach was applied to two model systems that show residual overall motion, when analyzed using all atoms as reference for the superimposing algorithm. In both cases, our algorithm was capable of eliminating residual covariances caused by the overall motion, while retaining internal covariances even for very distant atoms. A structural ensemble obtained for a 13-ns molecular dynamics simulation of the protein Ribonuclease T1 showed a covariance matrix of the corrected modes with significantly sharper contours after applying the bias-free separation.     

Functional form diagnostics for Cox's proportional hazards model

We propose a new type of residual and an easily computed functional form test for the Cox proportional hazards model. The proposed test is a modification of the omnibus test for testing the overall fit of a parametric regression model, developed by Stute, González Manteiga, and Presedo Quindimil (1998, Journal of the American Statistical Association93, 141-149), and is based on what we call censoring consistent residuals. In addition, we develop residual plots that can be used to identify the correct functional forms of covariates. We compare our test with the functional form test of Lin, Wei, and Ying (1993, Biometrika80, 557-572) in a simulation study. The practical application of the proposed residuals and functional form test is illustrated using both a simulated data set and a real data set.     

Detection of picogram amounts of nucleic acid by dot blot hybridization

An increasing number of human proteins isolated from cell sources are being produced for pharmaceutical use. Consequently, federal agencies have required the quantitative determination of residual nucleic acids that copurify with the potential protein products. We have conducted these assays in connection with our application for licensure of Alferon Injection. We report a sensitive dot blot hybridization assay that was used to quantitate picogram (or less) amounts of nucleic acids which copurified with human proteins isolated from recombinant (S. cerevisiae) or natural (leukocytes) sources.     

半湿润地区农田夏玉米氮肥利用率及土壤硝态氮动态变化

以土垫旱耕人为土为供试土壤,通过田间试验,研究了不同施氮量下（0、45、90、135和180 kg·hm^-2）夏玉米生育期土壤剖面NO₃^--N的变化特征、氮素利用率及施氮量与土壤NO^₃--N残留的关系.结果表明：在整个生育期内,土壤NO₃^--N含量均以0～20 cm土层最高,且施氮量越高,NO₃^--N含量也越高;0～60 cm土层NO₃^--N含量变化显著,60～100 cm土层NO₃^--N含量变化不大.夏玉米整个生育期,受玉米对氮素的需求和降雨的影响, 0～100 cm土层NO₃^--N累积量呈波动式降低趋势;当施氮量小于135 kg·hm^-2时,作物氮肥利用率随施氮量的增加而显著提高,但当施氮量超过135 kg·hm^-2时呈下降趋势. 氮肥农学利用率随施氮量的增加而减小,氮肥生理利用率随施氮量的增加而递增.土壤中残留NO₃^--N与施氮量呈极显著正线性相关关系 (R²=0.957^**,n=5);施氮处理籽粒产量显著高于不施氮处理(P<0.05）;施氮量与籽粒产量呈极显著正线性相关关系（R²=0.934^**,n=5）.在本试验条件下,夏玉米生长季适宜施氮量为135 kg·hm^-2.该施氮水平可保证效益和环境的双赢.     

A morphoelastic model for dermal wound closure

We develop a model of wound healing in the framework of finite elasticity, focussing our attention on the processes of growth and contraction in the dermal layer of the skin. The dermal tissue is treated as a hyperelastic cylinder that surrounds the wound and is subject to symmetric deformations. By considering the initial recoil that is observed upon the application of a circular wound, we estimate the degree of residual tension in the skin and build an evolution law for mechanosensitive growth of the dermal tissue. Contraction of the wound is governed by a phenomenological law in which radial pressure is prescribed at the wound edge. The model reproduces three main phases of the healing process. Initially, the wound recoils due to residual stress in the surrounding tissue; the wound then heals as a result of contraction and growth; and finally, healing slows as contraction and growth decrease. Over a longer time period, the surrounding tissue remodels, returning to the residually stressed state. We identify the steady state growth profile associated with this remodelled state. The model is then used to predict the outcome of rewounding experiments designed to quantify the amount of stress in the tissue, and also to simulate the application of pressure treatments.     

腹腔镜联合硬质胆道镜治疗复发性肝胆管结石的临床应用

目的:观察腹腔镜联合硬质胆道镜治疗复发性肝胆管结石的临床应用。方法:选取2013年1月-2014年1月期间在广州医科大学附属第一医院治疗的复发性肝胆管结石患者64例,随机分为研究组和对照组,研究组患者给予腹腔镜联合硬质胆道镜治疗,对照组患者采取开腹治疗。观察并比较两组患者的临床效果。结果:研究组患者手术出血量、手术时间、肛门排气时间、术后胆红素恢复时间、平均住院时间和抗生素应用时间均少于或短于对照组,差异均有统计学意义(均P0.05);研究组患者术后发生感染、胆漏、出血、结石残余与对照组比较差异均无统计学意义(均P0.05);研究组患者术后疼痛3例显著高于对照组的15例(P0.05)。结论:腹腔镜联合硬质胆道镜治疗复发性肝胆管结石对患者损伤小、手术过程中出血量少、结石取出率高、残留可能性小、结石复发率低、术后恢复快、并发症发生率低,其可行性和安全性高,适应范围广,值得推广应用。     

不同供氮量对二月兰产量、土壤无机氮残留及氮平衡的影响

研究华北冬绿肥二月兰对不同供氮水平的响应特征,确定实现绿肥高产高效的土壤适宜供氮量,可为华北集约化农田最大化发挥绿肥生态效应和优化春玉米/冬绿肥轮作体系氮素管理提供理论依据和技术参考.选取多年不施肥试验地设置供氮梯度试验,研究了不同供氮水平对冬绿肥二月兰翻压前地上部生物量累积、氮素吸收、土壤无机氮残留和冬绿肥季土壤氮素平衡的影响.结果表明: 在土壤无机氮含量较低(0～90 cm土层15 kg·hm^-2)条件下,施氮显著提高二月兰生物量和吸氮量.其中,施氮90 kg·hm^-2处理表现最高,绿肥生物量(干质量)和吸氮量分别为2031.0和42.0 kg·hm^-2;土壤无机氮残留量随施氮量增加而增加,且在施氮量高于60 kg·hm^-2后呈现快速增加趋势;随施氮量增加二月兰生长季的表观氮平衡表现出由亏缺到盈余的变化特征,在施氮量为60～90 kg·hm^-2条件下氮收支基本平衡.土壤供氮量(绿肥播前0～90 cm土壤无机氮含量与施氮量之和)与二月兰生物量、吸氮量和绿肥翻压前土壤无机氮含量的关系可以分别用二次、线性加平台和指数方程进行模拟,依据模型计算二月兰生物量最高值(2010 kg·hm^-2)时的播前土壤供氮量和绿肥翻压前土壤无机氮残留量分别是136和78 kg·hm^-2;而在二月兰吸氮量最高值40 kg·hm^-2时,二月兰生物量为1919 kg·hm^-2,相当于最高生物量的95%,绿肥翻压前土壤残留无机氮降低至57 kg·hm^-2,与之对应的播前土壤供氮量为105 kg·hm^-2,该值与目前华北地区优化施氮下玉米收获后土壤残留无机氮推荐含量(100 kg·hm^-2)基本相当.综合考虑绿肥的农学和环境效应,春玉米/冬绿肥轮作体系中二月兰播前土壤供氮量应控制在100～105 kg·hm^-2.     

利用剩余活性污泥合成聚羟基脂肪酸酯的研究进展

利用单一微生物发酵是现阶段获得聚羟基脂肪酸酯 (PHA) 的主要方式,但过高的生产成本限制了其大规模应用。近年来利用活性污泥菌群混合培养合成PHA被广泛研究。将剩余污泥处理与PHA合成相结合,不仅可以省去纯培养所必需的灭菌环节,同时可以实现剩余污泥的资源化利用。剩余污泥的水解酸化、菌群富集驯化及PHA合成受环境因素影响,深入的生物合成机制研究有助于混合培养合成PHA的推广应用。文中主要介绍利用剩余污泥合成PHA的可行性、影响剩余污泥水解酸化的因素、污泥菌群富集驯化合成PHA及其机制等方面的研究进展。     

术中胆道镜诊治肝胆管结石的应用（附64例报告）

术中应用胆道镜治疗胆道疾病６４例,使残余结石发生率由１１％下降至２％左右,认为纤维胆道镜对明确诊断减少残余结石的发生有重要价值。     

Immobilisation, remineralisation and residual effects in subsequent crops of dairy cattle slurry nitrogen compared to mineral fertiliser nitrogen

About 50–60% of dairy cattle slurry nitrogen is ammonium N. Part of the ammonium N in cattle slurry is immobilised due to microbial decomposition of organic matter in the slurry after application to soil. The immobilisation and the remineralisation influence the fertiliser value of slurry N and the amount of organic N that is retained in soil. The immobilisation and the remineralisation of 15 N-labelled dairy cattle slurry NH₄-N were studied through three growing seasons after spring application under temperate conditions. Effects of slurry distribution (mixing, layer incorporation, injection, surface-banding) and extra litter straw in the slurry on the plant utilisation of labelled NH₄-N from slurry were studied and compared to the utilisation of ¹⁵N-labelled mineral fertiliser. The initial immobilisation of slurry N was influenced by the slurry distribution in soil. More N was immobilised when the slurry was mixed with soil. Surface-banding of slurry resulted in significant volatilisation losses and less residual ¹⁵N in soil. Much more N was immobilised after slurry incorporation than after mineral fertiliser application. After 2.5 years the recovery of labelled N in soil (0–25 cm) was 46% for slurry mixed with soil, 42% for injected slurry, 22% for surface-banded slurry and 24% for mineral fertiliser N. The total N uptake in a ryegrass cover crop was 5–10 kg N/ha higher in the autumn after spring-application of cattle slurry (100–120 kg NH₄-N/ha) compared to the mineral fertiliser N reference, but the immobilised slurry N (labelled N) only contributed little to the extra N uptake in the autumn. Even in the second autumn after slurry application there was an extra N uptake in the cover crop (0–10 kg N/ha). The residual effect of the cattle slurry on spring barley N uptake was insignificant in the year after slurry application (equivalent to 3% of total slurry N). Eighteen months after application, 13% of the residual ¹⁵N in soil was found in microbial biomass whether it derived from slurry or mineral fertiliser, but the remineralisation rate (% crop removal of residual ¹⁵N) was higher for fertiliser- than for slurry-derived N, except after surface-banding. Extra litter straw in the slurry had a negligible influence on the residual N effects in the year after application. It is concluded that a significant part of the organic N retained in soil after cattle slurry application is derived from immobilised ammonium N, but already a few months after application immobilised N is stabilised and only slowly released. The immobilised N has negligible influence on the residual N effect of cattle slurry in the first years after slurry application, and mainly contributes to the long-term accumulation of organic N in soil together with part of the organic slurry N. Under humid temperate conditions the residual N effects of the manure can only be optimally utilised when soil is also covered by plants in the autumn, because a significant part of the residual N is released in the autumn, and there is a higher risk of N leaching losses on soils that receive cattle slurry regularly compared to soils receiving only mineral N fertilisers.     

氯嘧磺隆对土壤微生物群落结构的影响

采用磷脂脂肪酸(PLFA)法研究了黑龙江省苇河地区不同氯嘧磺隆施药历史下土壤微生物群落结构的差异, 并测定了土壤中氯嘧磺隆的残留量.结果表明：不同施药历史下氯嘧磺隆在土壤中的残留量均很低;随着施用氯嘧磺隆年限的增加,土壤微生物的PLFA总量减少, 革兰氏阴性菌/革兰氏阳性菌（GN/GP）和真菌/细菌比降低,土壤微生物的压力指数增加.主成分分析表明,氯嘧磺隆显著改变了大豆田土壤微生物群落结构.     

EEG classification of driver mental states by deep learning

Driver fatigue is attracting more and more attention, as it is the main cause of traffic accidents, which bring great harm to society and families. This paper proposes to use deep convolutional neural networks, and deep residual learning, to predict the mental states of drivers from electroencephalography (EEG) signals. Accordingly we have developed two mental state classification models called EEG-Conv and EEG-Conv-R. Tested on intra- and inter-subject, our results show that both models outperform the traditional LSTM- and SVM-based classifiers. Our major findings include (1) Both EEG-Conv and EEG-Conv-R yield very good classification performance for mental state prediction; (2) EEG-Conv-R is more suitable for inter-subject mental state prediction; (3) EEG-Conv-R converges more quickly than EEG-Conv. In summary, our proposed classifiers have better predictive power and are promising for application in practical brain-computer interaction .     

输尿管镜钬激光碎石术后残留结石的危险因素分析

目的：分析与输尿管镜钬激光碎石术后致使结石残留相关的临床危险因素。方法：选取我院214例接受输尿管镜钬激光碎石术的输尿管结石患者进行回顾性分析,对14个特征性临床因素与结石残留的关系应用单因素方差分析进行评价,对存在相关性的临床因素再应用计算机COX比例风险模型进行多因素分析。结果：全组患者结石残留率为42．52％（91／214）。单因素方差分析：ESWL史、惠侧肾功能、结石位置、结石最大径、击碎后最大径、术后第1日输液量、术后第1日尿量、术后下床时间、术后解痉利尿药使用与术后结石残留相关（P值均〈0．05）;经过COX比例风险模型检测,患侧肾功能、结石位置、击碎后最大径、是结石残留的危险因素（P〈0．05）,而术后第1日尿量及术后解痉利尿药使用是结石残留的保护因素（P〈0．05）。结论：患侧肾功能不良、结石位于上段、击碎后直径仍大易导致残留结石,而术后第1天尿量较多且适当应用解痉利尿药能减少残留结石。     

Residual structure in unfolded proteins

The denatured state ensemble (DSE) of unfolded proteins, once considered to be well-modeled by an energetically featureless random coil, is now well-known to contain flickering elements of residual structure. The position and nature of DSE residual structure may provide clues toward deciphering the protein folding code. This review focuses on recent advances in our understanding of the nature of DSE collapse under folding conditions, the quantification of the stability of residual structure in the DSE, the determination of the location and types of residues involved in thermodynamically significant residual structure and advances in detection of long-range interactions in the DSE.     

Potential sources of Triatoma infestans reinfesting peridomiciles identified by morphological characterization in Los Llanos,La Rioja,Argentina

The presence of Triatoma infestans in habitats treated with insecticides constitutes a frequent problem in endemic areas. Basing our study on the hypothesis that descendants of a residual population should be more similar to the pre-treatment population than to any other, we compared the indications of two quantitative morphological approaches. This study seeks to find the origin of 247 T. infestans from three populations found in two chicken coops and a goat corral after treatment with insecticides. The results obtained by quantitative morphology suggest that the T. infestans found between three-34 months after the application of insecticides formed mixed populations with insects derived from residual foci and neighbouring habitats. Our analyses also showed the presence of a phenotype which does not resemble neither the pre-treatment phenotype nor the one from neighbouring populations, suggesting the presence of a particular post-treatment phenotype. The heads size showed some variations in males from different populations and remained unchanged in females, which reinforces the hypothesis of an intraspecific competition for food with priority for females. This article presents, for the first time, the combined analysis of geometric morphometry of heads and antennal phenotypes to identify the composition of reinfesting populations.     

Alignment of optical maps.

We introduce a new scoring method for calculation of alignments of optical maps. Missing cuts, false cuts, and sizing errors present in optical maps are addressed by our alignment score through calculation of corresponding likelihoods. The size error model is derived through the application of Central Limit Theorem and validated by residual plots collected from real data. Missing cuts and false cuts are modeled as Bernoulli and Poisson events, respectively, as suggested by previous studies. Likelihoods are used to derive an alignment score through calculation of likelihood ratios for a certain hypothesis test. This allows us to achieve maximal descriminative power for the alignment score. Our scoring method is naturally embedded within a well known DP framework for finding optimal alignments.     

Enrichment and Purging of Human Embryonic Stem Cells by Detection of Cell Surface Antigens Using the Monoclonal Antibodies TG30 and GCTM-2

Human embryonic stem cells (hESC) can self-renew indefinitely in vitro, and with the appropriate cues can be induced to differentiate into potentially all somatic cell lineages. Differentiated hESC derivatives can potentially be used in transplantation therapies to treat a variety of cell-degenerative diseases. However, hESC differentiation protocols usually yield a mixture of differentiated target and off-target cell types as well as residual undifferentiated cells. For the translation of differentiated hESC-derivatives from the laboratory to the clinic, it is important to be able to discriminate between undifferentiated (pluripotent) and differentiated cells, and generate methods to separate these populations. Safe application of hESC-derived somatic cell types can only be accomplished with pluripotent stem cell-free populations, as residual hESCs could induce tumors known as teratomas following transplantation. Towards this end, here we describe a methodology to detect pluripotency associated cell surface antigens with the monoclonal antibodies TG30 (CD9) and GCTM-2 via fluorescence activated cell sorting (FACS) for the identification of pluripotent TG30^Hi-GCTM-2^Hi hESCs using positive selection. Using negative selection with our TG30/GCTM-2 FACS methodology, we were able to detect and purge undifferentiated hESCs in populations undergoing very early-stage differentiation (TG30^Neg-GCTM-2^Neg). In a further study, pluripotent stem cell-free samples of differentiated TG30^Neg-GCTM-2^Neg cells selected using our TG30/GCTM-2 FACS protocol did not form teratomas once transplanted into immune-compromised mice, supporting the robustness of our protocol. On the other hand, TG30/GCTM-2 FACS-mediated consecutive passaging of enriched pluripotent TG30^Hi-GCTM-2^Hi hESCs did not affect their ability to self-renew in vitro or their intrinsic pluripotency. Therefore, the characteristics of our TG30/GCTM-2 FACS methodology provide a sensitive assay to obtain highly enriched populations of hPSC as inputs for differentiation assays and to rid potentially tumorigenic (or residual) hESC from derivative cell populations.     

On nonlinear beta regression residuals

We proposed a new residual to be used in linear and nonlinear beta regressions. Unlike the residuals that had already been proposed, the derivation of the new residual takes into account not only information relative to the estimation of the mean submodel but also takes into account information obtained from the precision submodel. This is an advantage of the residual we introduced. Additionally, the new residual is computationally less intensive than the weighted residual. Recall that the computation of the latter involves an matrix, where n is the sample size. Obviously, that can be a problem when the sample size is very large. In contrast, our residual does not suffer from that. It can be easily computed even in large samples. Finally, our residual proved to be able to identify atypical observations as well as the weighted residual. We also propose new thresholds for residual plots and a scheme for the choice of starting values to be used in maximum likelihood point estimation in the class of nonlinear beta regression models. We report Monte Carlo simulation results on the behavior of different residuals. We also present and discuss two empirical applications; one uses the proportion of killed grasshoppers in an assay on the grasshopper Melanopus sanguinipes with the insecticide carbofuran and the synergist piperonyl butoxide, which enhances the toxicity of the insecticide, and the other uses simulated data. The results favor the new methodology we introduce.     

Behavior of pesticides (1): efficiency evaluation of pesticides.

The correlation equation for the concentration-mortality curve of a specific pesticide and a control pesticide was used to adapt the effectiveness data from residual activity tests to the corresponding chemical application concentration, to calculate the constant with the decreasing speed equation, and to calculate the application dose necessary to maintain an equal residual effect period by the same equation. The calculated value is the amount of pesticide needed to perform with the same efficiency as the control pesticide (effectiveness and period of effectiveness), which is vitally important to effectively select an appropriate pesticide.     

丹参多酚酸盐对维持性血液透析患者残余肾功能与钙磷代谢的影响

目的:探讨丹参多酚酸盐对维持性血液透析患者残余肾功能与钙磷代谢的影响。方法:2014年1月-2019年5月选择在本院肾内科就诊的终末期肾病患者72例,根据随机数字表法分为观察组与对照组各36例。所有患者都给予维持性血液透析治疗,在此基础上观察组给予丹参多酚酸盐治疗,持续3个月,记录残余肾功能与钙磷代谢变化情况。结果:治疗后观察组的总有效率为97.2%,高于对照组的83.3%(P<0.05)。两组治疗后的24 h尿量、肾小球滤过率(glomerular filtration rate,GFR)、血清转化生长因子β1(Transforming growth factorβ1,TGF-β1)和白介素-6(Interleukin-6,IL-6)低于治疗前,观察组也低于对照组(P<0.05)。两组治疗后的血钙值高于治疗前,观察组也高于对照组;两组治疗后的血磷值低于治疗前,观察组也低于对照组(P<0.05)。结论:丹参多酚酸盐在维持性血液透析患者中的应用有利于残余肾功能的恢复,调节钙磷代谢平衡,抑制炎症因子的表达,从而提高治疗效果。