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Mechanical Properties of Self-Assembled Microtubule Curved Protofilaments 自组装微管弯曲原丝的力学性能
Pub Date : 2020-03-31 DOI: 10.4236/jbise.2020.133003
R. Pidaparti, Divya Jakkam
The microtubule self-assembly process involves the basic building blocks, alpha and beta tubulins which spontaneously bind to one another through polymerization and under controlled intracellular conditions form protofilaments which in turn assemble into microtubules. The mechanical properties of the self-assembled protofilaments play an important role in formation of the microtubules. In this study, we investigate the mechanical properties of the experimentally self-assembled protofilaments (straight and curved) for under different loadings through 3D finite element analysis. Results of force-deformation and stiffness values obtained from the finite element analysis are presented. The results indicate that the stiffness and maximum stress properties change with varying protofilamant curvature. These force-deformation behaviors and stress distributions should help further understand the contribution of protofilaments mechanical properties in forming self-assembled microtubules.
微管自组装过程涉及基本的构建块,α和β微管蛋白,它们通过聚合自发地相互结合,并在受控的细胞内条件下形成原丝,进而组装成微管。自组装原丝的机械性能在微管的形成中起着重要作用。在本研究中,我们通过三维有限元分析研究了实验自组装原丝(直的和弯曲的)在不同载荷下的力学性能。给出了有限元分析得到的力变形和刚度值的结果。结果表明,刚度和最大应力特性随原丝曲率的变化而变化。这些力-变形行为和应力分布应有助于进一步了解原丝机械性能在形成自组装微管中的贡献。
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引用次数: 0
Building Quantitative Gene Regulatory Mechanism in Quorum Sensing in Pseudomonas aeruginosa Using Transcriptomic Data 利用转录组学数据构建铜绿假单胞菌群体感应的定量基因调控机制
Pub Date : 2020-02-28 DOI: 10.4236/jbise.2020.132002
Shaomin Yan, Guang Wu
A large amount of transcriptomic data provides opportunities 1) to verify the gene regulatory mechanism, which is usually obtained from a single experiment, at population level; 2) to uncover the gene regulatory mechanism at population level; and 3) to build a quantitatively gene regulatory mechanism. One of the best studied regulatory mechanisms in bacteria is the quorum sensing (QS), which plays an important role in regulation of bacteria population behaviors such as antibiotic production, biofilm formation, bioluminescence, competence, conjugation, motility and sporulation. Pseudomonas aeruginosa is a Gram-negative bacterium causing diseases in plants, animals, humans, and its biofilm and drug-resistance become great concerns in clinics. P. aeruginosa has three QS systems including a specific one for Pseudomonas. In this study, the transcriptomic data of P. aeruginosa were combined from 104 publications and QS gene expressions were analyzed under different experimental conditions. The results demonstrate the quantitatively regulatory mechanisms of QS genes at population level including 1) to rank and group QS-related genes according to their activity; 2) to quantitatively define the role of a single global regulator; 3) to find out the probability that a global regulator impacts QS genes and the probability that a QS gene responds to global regulators; and 4) to search for overlapped genes under four types of experimental conditions. These results provide integrative information on understanding the regulation of QS genes at population level.
大量的转录组学数据提供了机会1)在群体水平上验证基因调控机制,这通常是从单个实验中获得的;2) 揭示群体水平的基因调控机制;3)建立定量的基因调控机制。群体感应(QS)是细菌中研究得最好的调节机制之一,它在调节细菌群体行为中发挥着重要作用,如抗生素产生、生物膜形成、生物发光、能力、结合、运动和孢子形成。铜绿假单胞菌是一种引起植物、动物和人类疾病的革兰氏阴性菌,其生物膜和耐药性已成为临床关注的焦点。铜绿假单胞菌有三个QS系统,其中一个是针对假单胞菌的。在本研究中,结合来自104篇出版物的铜绿假单胞菌转录组学数据,分析了不同实验条件下QS基因的表达。结果证明了QS基因在群体水平上的定量调控机制,包括1)根据QS相关基因的活性对其进行排序和分组;2) 定量界定单一全球监管机构的作用;3) 找出全球调节因子影响QS基因的概率以及QS基因对全球调节因子作出反应的概率;以及4)在四种类型的实验条件下搜索重叠基因。这些结果为理解群体水平上QS基因的调控提供了综合信息。
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引用次数: 0
Purification of Full-Length β-Secretase Involved in Alzheimer’s Disease, and Proteomic Identification of Binding Partners 阿尔茨海默病相关β-分泌酶全长的纯化及结合伙伴的蛋白质组学鉴定
Pub Date : 2020-01-30 DOI: 10.4236/jbise.2020.131001
Lucy Ly, R. Parsons, B. Austen
β-Secretase (BACE1 or β-site APP cleaving enzyme) is an acid protease that releases the neurotoxic 40 - 42 residue peptides (β-amyloid or A-β) from its glycoprotein precursor, (APP or amyloid precursor protein) which when released in brain is thought to give rise to cognitive decline in patients with Alzheimer’s Disease. Most structural studies on β-secretase have previously been performed with recombinant forms of the protease, in which the transmembrane coding region has been deleted. However, interactions with proteins of the same species are best studied using the full-length β-secretase as interactions are likely to be influenced by the hydrophobic nature and localization of its transmembrane regions. Here we develop a multi-step purification procedure that isolates a complex containing BACE1 from recombinant human cells using mild detergents in a procedure that retains other proteins within the complex and remains active in its β-site APP cleaving activity. Some of these proteins, eg reticulon 4, are identified by proteomics, and are known by previous studies performed by others to regulate the activity of BACE1 against APP. These interactions may aid the development of small proteins and peptides that could inhibit the release of aggregated forms of β-amyloid, and thus be useful therapeutically.
β-分泌酶(BACE1或β位点APP切割酶)是一种酸性蛋白酶,可从其糖蛋白前体(APP或淀粉样蛋白前体)中释放神经毒性40 - 42残基肽(β-淀粉样蛋白或A-β),当其在大脑中释放时,被认为会引起阿尔茨海默病患者的认知能力下降。大多数关于β-分泌酶的结构研究以前都是用蛋白酶的重组形式进行的,其中跨膜编码区已被删除。然而,与同一物种的蛋白质的相互作用最好使用全长β分泌酶进行研究,因为相互作用可能受到其跨膜区域的疏水性和定位的影响。在这里,我们开发了一种多步骤的纯化程序,使用温和的洗涤剂从重组人细胞中分离出含有BACE1的复合体,该程序保留了复合体内的其他蛋白质,并保持其β位点APP切割活性。其中一些蛋白质,如reticulon 4,已经被蛋白质组学鉴定出来,并且在之前的研究中被其他人发现可以调节BACE1对抗APP的活性。这些相互作用可能有助于小蛋白和肽的发育,这些小蛋白和肽可以抑制β-淀粉样蛋白聚集形式的释放,因此在治疗上是有用的。
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引用次数: 0
The Dependence of the Miscibility, Stability and Compressibility of L-α Dioleoylphosphatidylcholine/Rutin Laurate Monolayer at the Air/Water on Temperature L-α二油基磷脂酰胆碱/月桂酸芦丁单分子膜在空气/水中的混溶性、稳定性和可压缩性与温度的关系
Pub Date : 2020-01-01 DOI: 10.4236/jbise.2020.137013
Anlong Li, Xiaolan Wang, Yu Duan, Liuya Wei
The miscibility, stability and compressibility of L-α dioleoylphosphatidylcholine/rutin laurate mixed monolayer at the air/water were investigated by Langmuir film balance to reveal the characteristic of the molecular interaction. The two components of DOPC/RL mixed monolayer were miscible throughout the mixture composition range and at three experimental temperatures of 10°C, 25°C and 37°C. At all experimental conditions, RL increased the compressibility and elasticity of the DOPC monolayer. Both the temperature and the composition of the membrane affected the form of intermolecular forces in the mixed monolayer.
采用Langmuir膜平衡法研究了L-α二酰基磷脂酰胆碱/月桂酸芦丁混合单层膜在空气/水中的混相性、稳定性和可压缩性,揭示了分子相互作用的特点。DOPC/RL混合单层两组分在混合物组成范围内和10℃、25℃和37℃三个实验温度下均可混相。在所有实验条件下,RL均提高了DOPC单层的压缩性和弹性。温度和膜的组成都影响了混合单层中分子间力的形式。
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引用次数: 0
A Deep Learning Interpretable Model for Novel Coronavirus Disease (COVID-19) Screening with Chest CT Images 基于胸部CT图像的新型冠状病毒病(COVID-19)筛查的深度学习可解释模型
Pub Date : 2020-01-01 DOI: 10.4236/jbise.2020.137014
E. Matsuyama
In this article, we propose a convolutional neural network (CNN)-based model, a ResNet-50 based model, for discriminating coronavirus disease 2019 (COVID-19) from Non-COVID-19 using chest CT. We adopted the use of wavelet coefficients of the entire image without cropping any parts of the image as input to the CNN model. One of the main contributions of this study is to implement an algorithm called gradient-weighted class activation mapping to produce a heat map for visually verifying where the CNN model is looking at the image, thereby, ensuring the model is performing correctly. In order to verify the effectiveness and usefulness of the proposed method, we compare the obtained results with that obtained by using pixel values of original images as input to the CNN model. The measures used for performance evaluation include accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and Matthews correlation coefficient (MCC). The overall classification accuracy, F1 score, and MCC for the proposed method (using wavelet coefficients as input) were 92.2%, 0.915%, and 0.839%, and those for the compared method (using pixel values of the original image as input) were 88.3%, 0.876%, and 0.766%, respectively. The experiment results demonstrate the superiority of the proposed method. Moreover, as a comprehensible classification model, the interpretability of classification results was introduced. The region of interest extracted by the proposed model was visualized using heat maps and the probability score was also shown. We believe that our proposed method could provide a promising computerized toolkit to help radiologists and serve as a second eye for them to classify COVID-19 in CT scan screening examination.
在本文中,我们提出了一个基于卷积神经网络(CNN)的模型,一个基于ResNet-50的模型,用于通过胸部CT区分2019冠状病毒病(COVID-19)和非COVID-19。我们采用不裁剪图像任何部分的整幅图像的小波系数作为CNN模型的输入。本研究的主要贡献之一是实现了一种称为梯度加权类激活映射的算法,用于生成热图,以直观地验证CNN模型正在查看图像的位置,从而确保模型正确执行。为了验证所提方法的有效性和实用性,我们将得到的结果与使用原始图像的像素值作为CNN模型输入得到的结果进行了比较。用于性能评价的指标包括准确性、敏感性、特异性、阳性预测值、阴性预测值、F1评分、Matthews相关系数(MCC)。本文方法(以小波系数为输入)的总体分类准确率为92.2%,F1评分为0.915%,MCC为0.839%,而对比方法(以原始图像像素值为输入)的总体分类准确率为88.3%,F1评分为0.86%,MCC为0.766%。实验结果证明了该方法的优越性。此外,作为一种可理解的分类模型,引入了分类结果的可解释性。利用热图将模型提取的感兴趣区域可视化,并显示概率得分。我们认为,我们提出的方法可以为放射科医生提供一个有前途的计算机化工具包,并作为他们在CT扫描筛查检查中对COVID-19进行分类的第二眼。
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引用次数: 17
Cross Entropy Based Sparse Logistic Regression to Identify Phenotype-Related Mutations in Methicillin-Resistant Staphylococcus aureus 基于交叉熵的稀疏逻辑回归识别耐甲氧西林金黄色葡萄球菌表型相关突变
Pub Date : 2020-01-01 DOI: 10.4236/jbise.2020.137016
B. Abapihi, M. Faisal, Ngoc Nguyen, Mera Kartika Delimayanti, Bedy Purnama, F. R. Lumbanraja, Dau Phan, Mamoru Kubo, K. Satou
Emergence of drug resistant bacteria is one of the serious problems in today’s public health. However, the relationship between genomic mutation of bacteria and the phenotypic difference of them is still unclear. In this paper, based on the mutation information in whole genome sequences of 96 MRSA strains, two kinds of phenotypes (pathogenicity and drug resistance) were learnt and predicted by machine learning algorithms. As a result of effective feature selection by cross entropy based sparse logistic regression, these phenotypes could be predicted in sufficiently high accuracy (100% and 97.87%, respectively) with less than 10 features. It means that we could develop a novel rapid test method in the future for checking MRSA phenotypes.
耐药细菌的出现是当今公共卫生的严重问题之一。然而,细菌基因组突变与其表型差异之间的关系尚不清楚。本文基于96株MRSA菌株全基因组序列的突变信息,通过机器学习算法学习并预测了两种表型(致病性和耐药性)。通过基于交叉熵的稀疏逻辑回归进行有效的特征选择,这些表型的预测准确率在10个以内,分别达到100%和97.87%。这意味着我们可以在未来开发一种新的快速检测MRSA表型的方法。
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引用次数: 1
Mitochondria Dynamically Transplant into Cells in Vitro and in Mice and Rescue Aerobic Respiration of Mitochondrial DNA-Depleted Motor Neuron NSC-34 线粒体体外和小鼠动态移植及线粒体dna缺失运动神经元NSC-34的有氧呼吸恢复
Pub Date : 2020-01-01 DOI: 10.4236/jbise.2020.139019
Xian P. Jiang, C. Baucom, R. Elliott
It has been reported that transplantation of pheochromocytoma P12 and hepatoma cells’ mitochondria improve the locomotive activity and prevent disease progress in experimental Parkinson’s disease rats. To prepare for mitochondrial transplantation study in human neurodegenerative diseases, we select human fibroblasts as mitochondrial donor because that fibroblasts share many characteristics with mesenchymal stromal cells (MSCs). We isolate human primary fibroblasts and develop a mitochondrial DNA (mtDNA)-depleted mouse motor neuron NSC-34 cells (NSC-34 ρ° cells). Fibroblast and NSC-34 cell’s mitochondria are co-cultured with NSC-34 ρ° cells. Mitochondrial transplantation is observed by fluorescent microscopy. Gene expression is determined by polymerase chain reaction (PCR) and real time PCR (qPCR). Also, mitochondria are injected to mice bearing mammary adenocarcinoma 4T1 cells. We find results as following: 1) There are abundant mitochondria in fibroblasts (337 ± 80 mitochondria per fibroblast). 42.4% of viable mitochondria are obtained by using differential centrifugation. The isolated mitochondria actively transplant into NSC-34 ρ° cells after co-culture. 2) Fibroblasts transfer mitochondria to human mammary adenocarcinoma MCF-7 cells. 3) There is no expression of HLA-I antigen in fibroblast’s mitochondria indicating they can be used for allogeneic mitochondrial transplantation without HLA antigen match. 4) PCR and qPCR show that NSC-34 ρ° cells lose mitochondrially encoded cytochrome c oxidase I (MT-CO1) and mitochondrially encoded NADH dehydrogenase 1 (MT-ND1) and upregulate expression of glycolysis-associated genes hexokinase (HK2), glucose transporter 1 (SLC2A1) and lactate dehydrogenase A (LDHA). 5) Transplantation of NSC-34 mitochondria restores MT-CO1 and MT-ND1 and downregulates gene expression of HK2, SLC2A1 and LDHA. 6) Normal mammary epithelial mitochondria successfully enter to 4T1 cells in mice. Subcutaneous injection of mitochondria is safe for mice. In summary, mitochondrial transplantation replenishes mtDNA and rescues aerobic respiration of diseased cells with mitochondrial dysfunction. Human primary fibroblasts are potential mitochondrial donor for mitochondrial transplantation study in human neurodegenerative diseases.
有报道称,移植嗜铬细胞瘤P12和肝癌细胞线粒体可改善实验性帕金森病大鼠的运动活性,防止疾病进展。为了为人类神经退行性疾病的线粒体移植研究做准备,我们选择人类成纤维细胞作为线粒体供体,因为成纤维细胞与间充质间质细胞(MSCs)具有许多共同的特征。我们分离了人原代成纤维细胞,并培养了线粒体DNA (mtDNA)缺失的小鼠运动神经元NSC-34细胞(NSC-34 ρ°细胞)。成纤维细胞和NSC-34细胞线粒体与NSC-34 ρ°细胞共培养。荧光显微镜观察线粒体移植。基因表达通过聚合酶链反应(PCR)和实时PCR (qPCR)检测。此外,将线粒体注射到携带乳腺腺癌4T1细胞的小鼠体内。结果表明:1)成纤维细胞线粒体丰富(每个成纤维细胞有337±80个线粒体)。差速离心获得42.4%的活线粒体。共培养后,分离的线粒体主动移植到NSC-34 ρ°细胞中。2)成纤维细胞将线粒体转移到人乳腺腺癌MCF-7细胞。3)成纤维细胞线粒体中未见HLA- 1抗原表达,可用于同种异体线粒体移植,无需HLA抗原匹配。4) PCR和qPCR结果显示,NSC-34 ρ°细胞线粒体编码的细胞色素c氧化酶I (MT-CO1)和NADH脱氢酶1 (MT-ND1)缺失,糖酵解相关基因己糖激酶(HK2)、葡萄糖转运蛋白1 (SLC2A1)和乳酸脱氢酶A (LDHA)表达上调。5)移植NSC-34线粒体恢复MT-CO1和MT-ND1,下调HK2、SLC2A1和LDHA基因表达。6)小鼠正常乳腺上皮线粒体成功进入4T1细胞。小鼠皮下注射线粒体是安全的。总之,线粒体移植可以补充线粒体dna,并挽救线粒体功能障碍的患病细胞的有氧呼吸。人原代成纤维细胞是人类神经退行性疾病线粒体移植研究的潜在线粒体供体。
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引用次数: 0
Discrimination between Dementia Groups and Healthy Elderlies Using Scalp-Recorded-EEG-Based Brain Functional Connectivity Networks 基于头皮记录脑电图的脑功能连接网络对痴呆组和健康老年人的区分
Pub Date : 2020-01-01 DOI: 10.4236/jbise.2020.137015
Sakura Nishijima, T. Yada, T. Yamazaki, Y. Kuroiwa, M. Nakane, K. Fujino, T. Hirai, Y. Baba, S. M. Yamada, Sho Tsukiyama
Objective: To establish a practical method for discriminating dementia groups and healthy elderlies, by using scalp-recorded electroencephalograms (EEGs). Methods: 16-ch EEGs were recorded during resting state for 39 dementia groups and 11 healthy elderlies. The connectivity between any two electrodes was estimated by synchronization likelihood (SL). The brain networks were constructed by normalized SL values. The present leave-one-out cross validation (LOOCV) required the Euclidean distance between any two subjects having 120-dimensional vectors concerned with the SL values for six frequency bands. In order to investigate factors which would affect the LOOCV results, principal component analysis (PCA) was applied to all the subjects. Results: The accuracy for the upper alpha yielded more than 80% and 70% in the dementia groups and the healthy elderlies, respectively. The LOOCV result could be explained in terms of brain networks such as executive control network (ECN) and default mode network (DMN) characterized by factor loadings of principal components. Conclusions: Dementia groups and healthy elderlies could be characterized by principal components of SL values between all the electrode pairs, even less connections, which revealed disruption and preservation of DMN and ECN. Significance: This study will provide a simple and practical method for discriminating dementia groups from healthy elderlies by scalp-recorded EEGs.
目的:建立一种实用的用头皮记录脑电图(eeg)区分痴呆人群与健康老年人的方法。方法:对39例痴呆组和11例健康老年人静息状态下的16-ch脑电图进行记录。通过同步似然(SL)估计任意两个电极之间的连通性。用归一化的SL值构建脑网络。目前的留一交叉验证(LOOCV)要求任何两个受试者之间的欧几里得距离具有120维向量,涉及6个频段的SL值。为了探讨影响LOOCV结果的因素,对所有受试者进行主成分分析(PCA)。结果:在痴呆组和健康老年人中,上α值的准确率分别超过80%和70%。LOOCV的结果可以用脑网络如执行控制网络(ECN)和默认模式网络(DMN)来解释,这些网络以主成分的因子负荷为特征。结论:痴呆组和健康老年人的所有电极对之间均存在主成分的SL值,甚至连通性更少,显示DMN和ECN的破坏和保存。意义:本研究将提供一种简单实用的通过头皮记录脑电图区分痴呆组和健康老年人的方法。
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引用次数: 1
High Sensitive Graphene Devices for Non-Invasive Early Diagnosis of Hyperthyroidism: A Feasibility Study 用于甲状腺机能亢进非侵入性早期诊断的高灵敏度石墨烯装置:可行性研究
Pub Date : 2019-12-16 DOI: 10.4236/jbise.2019.1212043
Avinash Yadav, I. Ali, A. Helmy, M. Rizkalla
This paper presents a novel approach with Graphene devices that are highly sensitive in detecting IR energy. Current non-imaging techniques like ultrasonography have been proposed for thyroid diagnosis with limitations on ability to detect low-temperature distribution around the hot spot at the starting stage of the thyroid hyperthyroidism. The energy distribution around hotspot is minimal at the beginning stage. This detection may require ultra-high sensitive materials to the IR energy. A computer modeling using COMSOL software shows the thermal energy simulation of a thyroid gland with single or multiple active nodules. Data collection of the energy levels and condition of thyroid in the human body support the work investigated in this study. The study conducted here has shown as low as 0.1 - 5 mW IR power can be detected based on the Graphene device sensitivity. The paper details the simulation and approach for this non-invasive diagnosis.
本文提出了一种利用石墨烯器件检测红外能量的新方法。目前已经提出了超声等非成像技术用于甲状腺诊断,但在甲状腺功能亢进症开始阶段检测热点周围低温分布的能力有限。在开始阶段,热点周围的能量分布是最小的。这种检测可能需要对IR能量具有超高灵敏度的材料。使用COMSOL软件的计算机建模显示了具有单个或多个活动结节的甲状腺的热能模拟。人体甲状腺能量水平和状况的数据收集支持了本研究的研究工作。在此进行的研究表明,基于石墨烯器件的灵敏度,可以检测到低至0.1-5mW的红外功率。本文详细介绍了这种无创诊断的模拟和方法。
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引用次数: 0
Potential Impact of Space Environments on Developmental and Maturational Programs Which Evolved to Meet the Boundary Conditions of Earth: Will Maturing Humans Be Able to Establish a Functional Biologic System Set Point under Non-Earth Conditions? 空间环境对发展和成熟计划的潜在影响,这些计划是为了满足地球的边界条件而进化的:成熟的人类能够在非地球条件下建立一个功能性的生物系统设定点吗?
Pub Date : 2019-12-10 DOI: 10.4236/jbise.2019.1212041
D. Hart
Mammalian development and maturation, particularly processes for humans have evolved in the context of the boundary conditions of Earth (i.e. 1 g gravity, geomagnetic field, background radiation) to yield functional individuals, although the process is not perfect and “errors” do occur. With the advent of spaceflight to low Earth orbit (the International Space Station), humans are now exposed to microgravity and increased exposure to radiation. However, thus far, only adult humans have served as astronauts, but this will likely change with plans to explore deep space and colonize planets. Thus, conception, fetal development, post-birth maturation, puberty and skeletal maturity will occur in the context of boundary conditions that did not shape human evolution and influence physiological and biomechanical systems designed to function within the Earth’s boundary conditions. Thus, processes utilizing the 1 g environment (i.e. walking upright) and the geomagnetic field (i.e. the electrical/biomagnetic basis of neural interactions) will have to adapt to new boundary conditions, providing opportunity for additional errors or alterations in processing during development which could impact functional outcomes at multiple levels. This review/perspective will discuss some of these issues and attempt to provide direction for addressing the potential issues to be encountered.
哺乳动物的发育和成熟,特别是人类的进化过程是在地球边界条件(即1 g重力、地磁场、背景辐射)的背景下进化而来的,以产生功能个体,尽管这个过程并不完美,确实会发生“错误”。随着进入近地轨道的太空飞行(国际空间站)的出现,人类现在暴露在微重力环境中,暴露在辐射中的次数增加。然而,到目前为止,只有成年人类担任过宇航员,但随着探索深空和殖民行星的计划,这种情况可能会改变。因此,受孕、胎儿发育、出生后成熟、青春期和骨骼成熟将发生在边界条件的背景下,这些边界条件不会影响人类的进化,也不会影响设计在地球边界条件下发挥作用的生理和生物力学系统。因此,利用1g环境(即直立行走)和地磁场(即神经相互作用的电/生物磁基础)的过程将不得不适应新的边界条件,为开发过程中的额外错误或处理变化提供机会,这可能会在多个层面上影响功能结果。本审查/观点将讨论其中一些问题,并试图为解决可能遇到的问题提供指导。
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引用次数: 3
期刊
生物医学工程(英文)
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