[^18F]标记表皮生长因子受体抑制剂显像剂全自动合成方法

目的：[^18F]标记表皮生长因子受体酪氨酸激酶抑制剂（EGFR—TKI）正电子显像剂在指导肿瘤分子靶向治疗中具有非常重要的作用。本文目的是找到一种全自动、适合日常使用的[^18F]标记EGFR-TKI正电子显像剂的全自动合成方法。方法：采用一步法合成[^18F]EGFR-TKIPET显像剂。首先合成4-[^18F]氟苯胺基,然后合成4-[^18F]氟苯胺基-6,7-二甲氧基喹唑啉。结果：整个合成过程大约60分钟,产率25％．35％（未校正）,放化纯度〉95％。结论：本文建立了一种适合临床日常应用的[^18F]EGFR-TKIPET显像剂的全自动合成方法。该方法对于进一步开发新型[^18F]标记的表皮生长因子受体抑制剂PET显像具有重要价值。     

New insights into the de novo gene synthesis using the automatic kinetics switch approach

Here we present a simple, highly efficient, universal automatic kinetics switch (AKS) gene synthesis method that enables synthesis of DNA up to 1.6 kbp from 1 nM oligonucleotide with just one polymerase chain reaction (PCR) process. This method eliminates the interference between the PCR assembly and amplification in one-step gene synthesis and simultaneously maximizes the amplification of emerged desired DNA by using a pair of flanked primers. In addition, we describe an analytical model of PCR gene synthesis based on the thermodynamics and kinetics of DNA hybridization. The kinetics difference between standard PCR amplification and one-step PCR gene synthesis is analyzed using this model and is validated using real-time gene synthesis with eight gene segments (318-1656 bp). The effects of oligonucleotide concentration, stringency of annealing temperature, annealing time, extension time, and PCR buffer conditions are examined systematically. Analysis of the experimental results leads to new insights into the gene synthesis process and aids in optimizing gene synthesis conditions. We further extend this method for multiplexing gene assembly with a total DNA length up to 5.74 kbp from 1 nM oligonucleotide.     

Continual improvement of nasopharyngeal carcinoma segmentation with less labeling effort

PurposeConvolutional neural networks (CNNs) offer a promising approach to automated segmentation. However, labeling contours on a large scale is laborious. Here we propose a method to improve segmentation continually with less labeling effort.MethodsThe cohort included 600 patients with nasopharyngeal carcinoma. The proposed method was comprised of four steps. First, an initial CNN model was trained from scratch to perform segmentation of the clinical target volume. Second, a binary classifier was trained using a secondary CNN to identify samples for which the initial model gave a dice similarity coefficient (DSC) < 0.85. Third, the classifier was used to select such samples from the new coming data. Forth, the final model was fine-tuned from the initial model, using only selected samples.ResultsThe classifier can detect poor segmentation of the model with an accuracy of 92%. The proposed segmentation method improved the DSC from 0.82 to 0.86 while reducing the labeling effort by 45%.ConclusionsThe proposed method reduces the amount of labeled training data and improves segmentation by continually acquiring, fine-tuning, and transferring knowledge over long time spans.     

Ontogenetic trajectory and allometry of Diplonychus rusticus (Fabricius), an Oriental aquatic bug (Hemiptera: Belostomatidae) from the Western Ghats of India

Despite being one of the dominant groups in freshwater ecosystems, morphological and ontogenetic studies on aquatic Hemiptera have received little attention in the Oriental region. We present the ontogenetic trajectory and allometry of the widespread Oriental belostomatid species, Diplonychus rusticus (Fabricius) for the first time. We have measured nine different morphological variables throughout the growth of the bug using both field captured and laboratory reared specimens. Our results suggest that the developmental instars can be distinguished by the size variables, as seen in the Principal Component Analysis. On the basis of a CHAID (Chi-squared Automatic Interaction Detection) based regression tree, we also show that the characters – total length without head and maximum width – prove to be adequate for effective instar identification. The multivariate allometric growth pattern shows that different body parts exhibit different types of allometry. This is apparent in the allometry exhibited by forelegs and mid and hind legs, which show allometry of opposite polarities. This may be due to the different functions attributed to these body parts. Our results show that the growth pattern in D. rusticus is comparable with the New World genus Belostoma, suggesting a conserved growth pattern in the family Belostomatidae.     

Automatic identification of large collections of protein-coding or rRNA sequences

The number of available genomic sequences is growing very fast, due to the development of massive sequencing techniques. Sequence identification is needed and contributes to the assessment of gene and species evolutionary relationships. Automated bioinformatics tools are thus necessary to carry out these identification operations in an accurate and fast way. We developed HoSeqI (Homologous Sequence Identification), a software environment allowing this kind of automated sequence identification using homologous gene family databases. HoSeqI is accessible through a Web interface (http://pbil.univ-lyon1.fr/software/HoSeqI/) allowing to identify one or several sequences and to visualize resulting alignments and phylogenetic trees. We also implemented another application, MultiHoSeqI, to quickly add a large set of sequences to a family database in order to identify them, to update the database, or to help automatic genome annotation. Lately, we developed an application, ChiSeqI (Chimeric Sequence Identification), to automate the processes of identification of bacterial 16S ribosomal RNA sequences and of detection of chimeric sequences.     

LigBuilder: A Multi-Purpose Program for Structure-Based Drug Design

We have developed a new multi-purpose program, LigBuilder, for structure-based drug design. Within the structural constraints of the target protein, LigBuilder builds up ligands step by step using a library of organic fragments. Various operations, such as growing, linking, and mutation, have been implemented to manipulate molecular structures. The user can choose either growing or linking strategies for ligand construction and a genetic algorithm is adopted to control the whole construction process. Binding affinities of the ligands are estimated by an empirical scoring function and the bioavailabilities are evaluated by a set of chemical rules. Using thrombin and dihydrofolate reductase as examples, we have demonstrated that LigBuilder is able to generate chemical structures similar to the known ligands.     

基于深度学习的红外相机动物影像人工智能识别：以东北虎豹国家公园为例

为解决大量红外相机监测影像数据量庞大、亟待快速和自动识别的问题,本研究以东北虎豹国家公园为例,应用卷积神经网络,通过深度学习算法对红外相机影像实现物种自动识别。本研究选择8个物种的红外相机视频影像,以50帧率均匀采集成图片格式,每个物种筛选不同角度、不同环境条件的图片,建立图片数据集,训练集2 074张,测试集519张。对图片进行目标打框、信息标注,选用darknet框架下的YOLO v3模型进行训练,首先不区分昼（RGB）夜（灰度）图像进行训练,再区分昼夜进行训练,最后分别对昼夜图像利用微调（fine-tune）进行训练。研究初步结果显示,基于YOLO v3模型对自然条件下拍摄的红外相机图像进行物种自动识别能够一定程度减轻人力负担,但其效果还需通过完善数据集进行提升。fine-tune在小数据集时或可作为辅助。模型对8个物种识别的平均精确率达到 84.9%~96.0%,且模型收敛。       

Vessel noise cuts down communication space for vocalizing fish and marine mammals

Anthropogenic noise across the world's oceans threatens the ability of vocalizing marine species to communicate. Some species vocalize at key life stages or whilst foraging, and disruption to the acoustic habitat at these times could lead to adverse consequences at the population level. To investigate the risk of these impacts, we investigated the effect of vessel noise on the communication space of the Bryde's whale Balaenoptera edeni, an endangered species which vocalizes at low frequencies, and bigeye Pempheris adspersa, a nocturnal fish species which uses contact calls to maintain group cohesion while foraging. By combining long‐term acoustic monitoring data with AIS vessel‐tracking data and acoustic propagation modelling, the impact of vessel noise on their communication space was determined. Routine vessel passages cut down communication space by up to 61.5% for bigeyes and 87.4% for Bryde's whales. This influence of vessel noise on communication space exceeded natural variability for between 3.9 and 18.9% of the monitoring period. Additionally, during the closest point of approach of a large commercial vessel, <10 km from the listening station, the communication space of both species was reduced by a maximum of 99% compared to the ambient soundscape. These results suggest that vessel noise reduces communication space beyond the evolutionary context of these species and may have chronic effects on these populations. To combat this risk, we propose the application or extension of ship speed restrictions in ecologically significant areas, since our results indicate a reduction in sound source levels for vessels transiting at lower speeds.     

留置导尿生理性自动计量排放器的研制和临床应用

为使截瘫等病人的膀胱仍能象在生理情况下贮存和排放尿液,有效的训练膀胱,并自动准确统计尿量。利用传感、微电脑技术研制出一留置导尿生理性自动计量排放器,初步用于临床50例病人的观察,减少人力,方便护理,效果满意。此仪器还可用于大手术术中术后、及休克等病人的尿量监护。可减少逆行性尿路感染,可推广使用。现报告如下:     

Neural control of quadrupedal and bipedal stance: implications for the evolution of erect posture

The transition among hominids from quadrupedalism to bipedalism resulted in modifications in their musculoskeletal morphology. It is unclear, however, whether changes in the circuitry of the CNS were also necessary in order to accommodate the unique balance requirements of two-limb support. This study addresses the issue of modifications in control strategies by investigating the rapid, automatic postural responses of feline and human subjects to sudden disturbances of balance in the anteroposterior (AP) direction while they stand quadrupedally and bipedally on movable platforms. Postural responses are characterized in terms of segmental adjustments, generated AP shear forces, and electromyographic activity. Feline and human subjects correct posture similarly when standing quadrupedally. Furthermore, both species correct stance primarily with their hindlimbs and use their forelimbs as supportive struts. In contrast, both species use completely different correctional strategies when standing bipedally. Morphological restrictions, however, prevent cats from adopting the pillar-like plantigrade posture of human beings. Thus, the correctional strategies of bipedal cats are distinct from those of bipedal human subjects. It is concluded that 1) automatic postural response patterns of quadrupedal Felis and bipedal Homo reflect the different biomechanical characteristics of the initial postures rather than species differences in CNS circuitry controlling stance; 2) hindlimb-dominated posture control is probably a common and relatively ancient pattern; and 3) reorganization of hominid CNS circuitry was probably unnecessary because hindlimb control was already a feature of the system.