Cloning and Functional Characterization of Dog OCT1 and OCT2: Another Step in Exploring Species Differences in Organic Cation Transporters

OCT1 and OCT2 are polyspecific membrane transporters that are involved in hepatic and renal drug clearance in humans and mice. In this study, we cloned dog OCT1 and OCT2 and compared their function to the human and mouse orthologs. We used liver and kidney RNA to clone dog OCT1 and OCT2. The cloned and the publicly available RNA-Seq sequences differed from the annotated exon-intron structure of OCT1 in the dog genome CanFam3.1. An additional exon between exons 2 and 3 was identified and confirmed by sequencing in six additional dog breeds. Next, dog OCT1 and OCT2 were stably overexpressed in HEK293 cells and the transport kinetics of five drugs were analyzed. We observed strong differences in the transport kinetics between dog and human orthologs. Dog OCT1 transported fenoterol with 12.9-fold higher capacity but 14.3-fold lower affinity (higher K_M) than human OCT1. Human OCT1 transported ipratropium with 5.2-fold higher capacity but 8.4-fold lower affinity than dog OCT1. Compared to human OCT2, dog OCT2 showed 10-fold lower transport of fenoterol and butylscopolamine. In conclusion, the functional characterization of dog OCT1 and OCT2 reported here may have implications when using dogs as pre-clinical models as well as for drug therapy in dogs.     

The Potentiality of Plant-Derived Nanovesicles in Human Health—A Comparison with Human Exosomes and Artificial Nanoparticles

Research in science and medicine is witnessing a massive increases in literature concerning extracellular vesicles (EVs). From a morphological point of view, EVs include extracellular vesicles of a micro and nano sizes. However, this simplistic classification does not consider both the source of EVs, including the cells and the species from which Evs are obtained, and the microenvironmental condition during EV production. These two factors are of crucial importance for the potential use of Evs as therapeutic agents. In fact, the choice of the most suitable Evs for drug delivery remains an open debate, inasmuch as the use of Evs of human origin may have at least two major problems: (i) autologous Evs from a patient may deliver dangerous molecules; and (ii) the production of EVs is also limited to cell factory conditions for large-scale industrial use. Recent literature, while limited to only a few papers, when compared to the papers on the use of human EVs, suggests that plant-derived nanovesicles (PDNV) may represent a valuable tool for extensive use in health care.     

莫斯科中国贸易中心工程防止结构连续倒塌设计

建筑抗倒塌问题近年来在欧美国家得到广泛关注。结合莫斯科中国贸易中心工程的防止结构连续倒塌设计,比较了国外一些相关设计规范和标准之间的相互关系,提出满足俄罗斯规范要求的防止连续倒塌设计计算方法,并将其与正常情况下的结构计算进行比较,找出其中带规律性的问题。     

浅析学生公寓卫生间渗漏原因及防治

通过分析学生公寓卫生间出现渗漏的原因,提出了相应的防治措施及处理方法。     

莺-琼盆地纵横波速度特征与AVO响应特征的关系研究

在莺-琼盆地,气层表现出了多种多样的AVO特征,有的为"Ⅲ"类,有的为"Ⅳ"类或"Ⅱ"类,有的偏离背景,有的与背景一致,这些复杂多样的AVO特征为应用AVO技术进行流体检测带来了较大的困难.为此,本文对近百口已钻井储层的AVO特征与纵、横波速度特征的关系进行了研究,并对产生这种关系的原因进行了详细分析,结果表明储层的纵...     

Challenges in Metabolomics-Based Tests,Biomarkers Revealed by Metabolomic Analysis,and the Promise of the Application of Metabolomics in Precision Medicine

Metabolomics helps identify metabolites to characterize/refine perturbations of biological pathways in living organisms. Pre-analytical, analytical, and post-analytical limitations that have hampered a wide implementation of metabolomics have been addressed. Several potential biomarkers originating from current targeted metabolomics-based approaches have been discovered. Precision medicine argues for algorithms to classify individuals based on susceptibility to disease, and/or by response to specific treatments. It also argues for a prevention-based health system. Because of its ability to explore gene–environment interactions, metabolomics is expected to be critical to personalize diagnosis and treatment. Stringent guidelines have been applied from the very beginning to design studies to acquire the information currently employed in precision medicine and precision prevention approaches. Large, prospective, expensive and time-consuming studies are now mandatory to validate old, and discover new, metabolomics-based biomarkers with high chances of translation into precision medicine. Metabolites from studies on saliva, sweat, breath, semen, feces, amniotic, cerebrospinal, and broncho-alveolar fluid are predicted to be needed to refine information from plasma and serum metabolome. In addition, a multi-omics data analysis system is predicted to be needed for omics-based precision medicine approaches. Omics-based approaches for the progress of precision medicine and prevention are expected to raise ethical issues.     

超、高超声速大长细比飞行器气动特性快速计算

将牛顿碰撞类方法推广应用于超、高超声速细长体导弹的气动特性预测.根据飞行器的外形特征,将外形分成几个部分,根据各自几何特点和流场特性,对不同部分及其迎风面和背风面选用不同的方法,计算方法适用于Ma=3~25、攻角0~30°范围内大长细比导弹类飞行器的气动力特性快速计算.经过与风洞试验数据的对比,证明此方法具有计算速度快、精度高的特点.     

低合金钢靶板受尖头弹冲击的变形与断裂

研究了低合金钢板在尖头弹冲击条件下的侵彻过程,讨论了应力条件和材料冶金质量对损伤和断裂的影响。结果表明,在侵彻过程前期靶材主要表现为三向压应力下的塑性流动;中期,靶材挤压流动,靶材内部的流速差造成剪切变形,并导致沿轧制偏析带的开裂;后期,靶材在剧烈剪切作用下剪切变形、局部失稳、形成剪切带和沿剪切带的开裂或撕裂。断裂按微孔聚集型机制进行。通常所谓花瓣型开裂实质上就是上述在切应力作用下的剪切撕裂。     

鲜红斑痣光动力治疗数学模型及临床验证

为了研究光动力治疗(PDT)中各个因素作用的规律,帮助临床采取有效的治疗方案,针对鲜红斑痣(PWS)组织特性,将光动力治疗中组织光分布、单线态氧产生、光敏剂漂白过程和光敏剂扩散过程结合起来,建立适合于光动力治疗鲜红斑痣病变的系统模型。利用建立的模型,对临床中出现的第二光斑治疗效果差的问题进行仿真研究,发现影响其治疗效果的因素,并通过仿真实验提出改进其治疗效果的新方案。通过临床实验,证明了新方案的有效性和模型的有效性。研究结果说明,针对特定的病例条件建立仿真模型,通过仿真实验可以为临床和理论研究提供一种有效的分析方法。     

基于分段信噪比加权的GPS定位方法

在基于GPS的飞行器定位中,GPS卫星的情况与地面不同,传统的GPS选星算法有局限性.为了实现飞行器快速、可靠的定位,提出了一种新的基于分段信噪比加权的GPS定位方法.实验表明,相对传统选星算法,本方法的定位稳定性更好、精度更高、计算时间较短,能够满足飞行器快速、可靠定位的要求.