Single cell biology beyond the era of antibodies: relevance,challenges, and promises in biomedical research

Research of the past two decades has proved the relevance of single cell biology in basic research and translational medicine. Successful detection and isolation of specific subsets is the key to understand their functional heterogeneity. Antibodies are conventionally used for this purpose, but their relevance in certain contexts is limited. In this review, we discuss some of these contexts, posing bottle neck for different fields of biology including biomedical research. With the advancement of chemistry, several methods have been introduced to overcome these problems. Even though microfluidics and microraft array are newer techniques exploited for single cell biology, fluorescence-activated cell sorting (FACS) remains the gold standard technique for isolation of cells for many biomedical applications, like stem cell therapy. Here, we present a comprehensive and comparative account of some of the probes that are useful in FACS. Further, we illustrate how these techniques could be applied in biomedical research. It is postulated that intracellular molecular markers like nucleostemin (GNL3), alkaline phosphatase (ALPL) and HIRA can be used for improving the outcome of cardiac as well as bone regeneration. Another field that could utilize intracellular markers is diagnostics, and we propose the use of specific peptide nucleic acid probes (PNPs) against certain miRNAs for cancer surgical margin prediction. The newer techniques for single cell biology, based on intracellular molecules, will immensely enhance the repertoire of possible markers for the isolation of cell types useful in biomedical research.     

An effective amperometric biosensor based on graphene modified gold nanowire arrays for glucose detection

A novel glucose biosensor based on graphene nanosheets （GNs） modified gold nanowire arrays （AuN- WAs） electrode was constructed. Highly ordered gold nanowire arrays were prepared by direct electrodeposition in anodic aluminum oxide templates. GNs were synthe- sized through a public route involving graphite oxidation, exfoliation, and chemical reduction. Field emission scan- ning electron microscope and high-resolution transmission electron microscope were employed to characterize the as- prepared AuNWAs and GNs. Glucose oxidase was immobilized on the surface of GNs-AuNWAs modified electrode via a cross-linking method. The cyclic voltam- metry results showed that the GNs-AuNWAs-based glu- cose biosensors have high catalysis activity to hydrogen peroxide （H2O2） than those modified with GNs or AuN- WAs only. Furthermore, amperometric response was employed to detect glucose concentration owing to its simplicity, high selectivity, and relative low cost. Glucose biosensors based on GNs-AuNWAs showed excellent performance with high sen- sitivity of 40.25 μA cm^-2 （mmol/L）^-1, low detection limit of 0.02 mmol/L, and a linear range from 0.02 to 3 mmol/L.     

基于局部紧耦合结构的模块性优化社区检测方法

利用局部紧耦合结构提升社区检测的模块性优化质量.首先,定义了4类边缘紧耦合结构,并提出了一种具有线性复杂度的边缘紧耦合结构挖掘算法.其次,分别选择k-clique,k-clan,k-plex结构作为核心紧耦合结构,并以长结构优先和短结构优先2种策略将边缘与核心紧耦合结构合并.然后,将合并后的局部紧耦合结构融入模块性优化过程,提出了一种NFN算法.该算法将每个局部紧耦合结构初始化为独立社区,不断凝聚模块性增量最大的2个社区,直至找到预定义数量的社区.6个真实数据集上针对外部指标和内部指标的实验结果均表明,相比于传统的FN算法,NFN算法能发现更高质量的社区.在参数设置方面,长结构优先策略优于短结构优先策略,且采用k-clique结构作为核心紧耦合结构优于采用其他结构.因此,长结构优先策略结合k-clique成为NFN算法的最佳参数组合.     

Routes and machinery of primary cilium biogenesis

Primary cilia are solitary, microtubule-based protrusions of the cell surface that play fundamental roles as photosensors, mechanosensors and biochemical sensors. Primary cilia dysfunction results in a long list of developmental and degenerative disorders that combine to give rise to a large spectrum of human diseases affecting almost any major body organ. Depending on the cell type, primary ciliogenesis is initiated intracellularly, as in fibroblasts, or at the cell surface, as in renal polarized epithelial cells. In this review, we have focused on the routes of primary ciliogenesis placing particular emphasis on the recently described pathway in renal polarized epithelial cells by which the midbody remnant resulting from a previous cell division event enables the centrosome for initiation of primary cilium assembly. The protein machinery implicated in primary cilium formation in epithelial cells, including the machinery best known for its involvement in establishing cell polarity and polarized membrane trafficking, is also discussed.     

Backstepping approach to the adaptive regulator design for a one-dimensional wave equation with general input harmonic disturbance

This paper considers the parameter estimation and stabilization of an unstable one-dimensional wave equation with matched general harmonic disturbance at the controlled end. The backstepping method for infinite-dimensional system is adopted in the design of the adaptive regulator. It is shown that the resulting closed-loop system is asymptotically stable. Meanwhile, the estimated parameter is shown to be convergent to the unknown parameter as time goes to infinity.     

Glutenin macropolymer particles size distribution of six wheat varieties in eastern China

Size distribution of glutenin macropolymer(GMP) particles significantly affects the quality of final products in wheat. Six wheat varieties in eastern China were used for investigating the GMP content, particle size distribution and their relation. The results showed that the particle diameter of GMP changed from 0.38 μm to 269 μm. A typical bimodal curve of volume distribution of particles with peak values ranged from 4.44 μm to 5.36 μm and from 45.76 μm to 116.30 μm, respectively. Number distribution of particles showed the typical population with peak values in the range of 0.57-1.00 μm. Proportions of granules 12 μm, 12-80 μm and 80 μm were in the range of 17.1%-47.8%, 32.1%-50.3% and 10.2%-38.1% of total volume, respectively. The content of GMP was negatively correlated with the volume of GMP particles 12 μm, but positively correlated with the volume of particles 80 μm. The results suggested that the greater percentage of larger GMP particles is, the more GMP content there is in wheat grain.     

Telomerase and drug resistance in cancer

It is well known that a decreased expression or inhibited activity of telomerase in cancer cells is accompanied by an increased sensitivity to some drugs (e.g., doxorubicin, cisplatin, or 5-fluorouracil). However, the mechanism of the resistance resulting from telomerase alteration remains elusive. There are theories claiming that it might be associated with telomere shortening, genome instability, hTERT translocation, mitochondria functioning modulation, or even alterations in ABC family gene expression. However, association of those mechanisms, i.e., drug resistance and telomerase alterations, is not fully understood yet. We review the current theories on the aspect of the role of telomerase in cancer cells resistance to therapy. We believe that revealing/unravelling this correlation might significantly contribute to an increased efficiency of cancer cells elimination, especially the most difficult ones, i.e., drug resistant.     

Transient pressure analysis for the reactor core and containment of a HTGR after a primary loop pressure boundary break accident

The pressure variances in the reactor core and containment of a High Temperature Gas-cooled Reactor (HTGR) after a primary loop pressure boundary break accident determine the structural integrity and safety of the reactor. Based on mass conservation, energy conservation and state equations, explicit formulae for the transient pressure and temperature variances in the pressure vessels were deduced, and a set of differential equations for the transient pressure and temperature variances in the containment were developed. Numerical simulation was also conducted to investigate the transient pressure and temperature variances in the pressure vessels and containment. The results show that energy transformation due to expansion work cannot be neglected. The maximum pressure in the containment could increase by 40 percent due to blockage caused by air in the containment. Detailed numerical simulations of the transient pressure and temperature variance in the reactor core flow passages were also conducted. The results show that the pressures acting on the reactor core and containment are below acceptable values.     

The age of synthesis: From cognitive science to converging technologies and hereafter

This paper describes the development of two of the most important scientific disciplines in the last quarter of the 20th century, cognitive science, which emerged in 1975, and nano-bio-info-cogno (NBIC) converging technologies, which emerged in 2000. In this century, we will achieve cross-disciplinary integration, innovation in comprehensive knowledge and comprehensive devel opment in human resources. NBIC converging technologies will greatly expand human cognition and communication, improve human health, enhance social outcomes, strengthen national security and unify science and education. Cognitive science and converging technologies will have major effects on the future human development. I argue that the 21st century represents an age of synthesis, reflected in the continual reintegration between scientific disciplines in recent times. This new age of synthesis will require innovations in thought and methodology that differ from those underlying the age of analysis in the 20th century. I predict that these developments will allow every individual to realize comprehensive development. Accordingly, the education system will be transformed, and a comprehensive human resources system will be created.