The Role of Cell Cycle Regulators in Cell Survival—Dual Functions of Cyclin-Dependent Kinase 20 and p21Cip1/Waf1

The mammalian cell cycle is important in controlling normal cell proliferation and the development of various diseases. Cell cycle checkpoints are well regulated by both activators and inhibitors to avoid cell growth disorder and cancerogenesis. Cyclin dependent kinase 20 (CDK20) and p21^Cip1/Waf1 are widely recognized as key regulators of cell cycle checkpoints controlling cell proliferation/growth and involving in developing multiple cancers. Emerging evidence demonstrates that these two cell cycle regulators also play an essential role in promoting cell survival independent of the cell cycle, particularly in those cells with a limited capability of proliferation, such as cardiomyocytes. These findings bring new insights into understanding cytoprotection in these tissues. Here, we summarize the new progress of the studies on these two molecules in regulating cell cycle/growth, and their new roles in cell survival by inhibiting various cell death mechanisms. We also outline their potential implications in cancerogenesis and protection in heart diseases. This information renews the knowledge in molecular natures and cellular functions of these regulators, leading to a better understanding of the pathogenesis of the associated diseases and the discovery of new therapeutic strategies.     

In Silico/In Vitro Hit-to-Lead Methodology Yields SMYD3 Inhibitor That Eliminates Unrestrained Proliferation of Breast Carcinoma Cells

SMYD3 is a lysine methyltransferase that regulates the expression of over 80 genes and is required for the uncontrolled proliferation of most breast, colorectal, and hepatocellular carcinomas. The elimination of SMYD3 restores normal expression patterns of these genes and halts aberrant cell proliferation, making it a promising target for small molecule inhibition. In this study, we sought to establish a proof of concept for our in silico/in vitro hit-to-lead enzyme inhibitor development platform and to identify a lead small molecule candidate for SMYD3 inhibition. We used Schrodinger^® software to screen libraries of small molecules in silico and the five compounds with the greatest predicted binding affinity within the SMYD3 binding pocket were purchased and assessed in vitro in direct binding assays and in breast cancer cell lines. We have confirmed the ability of one of these inhibitors, Inhibitor-4, to restore normal rates of cell proliferation, arrest the cell cycle, and induce apoptosis in breast cancer cells without affecting wildtype cell behavior. Our results provide a proof of concept for this fast and affordable small molecule hit-to-lead methodology as well as a promising candidate small molecule SMYD3 inhibitor for the treatment of human cancer.     

二甲苯吸附分离装置吸附塔压力控制的优化

介绍了二甲苯吸附分离装置模拟移动床工艺技术,针对吸附塔压力控制初期难以满足要求的问题,通过分析工艺过程和压送循环流量控制的特点,对压送循环流量控制进行了优化,解决了压送循环流量在区域切换时无法稳定控制的问题;采用A/B塔塔底压力的交叉控制策略,使得吸附塔压力始终保持稳定,满足控制精度要求。     

应用于钠冷快堆的超临界二氧化碳动力转换系统研究

超临界二氧化碳（SCO₂）布雷顿循环由于高效、紧凑和可避免钠水反应等特性而成为钠冷快堆的理想动力转换系统。本文以1 200 MWe大型池式钠冷快堆为系统热源，钠回路温度及热负荷为循环系统运行边界，对比研究了不同SCO₂布雷顿循环系统性能和关键设备性能的变化规律。研究发现，级间冷却再压缩循环与钠冷快堆热源特性匹配性最佳，且循环效率最高（40.7%）。进而研究了不同运行参数对级间冷却再压缩循环效率的影响规律，给出了循环系统效率对各关键影响因素的敏感度，发现循环系统效率对冷端参数的敏感度最强，其次为分流比和透平入口参数，对主压缩机级间压比的敏感度最弱。     

Development of a procedure writers’ guide framework: Integrating the procedure life cycle and reflecting on current industry practices

The current study aims to advance a procedure development process that will create procedures as effective safeguards. Several past incidents identified that many current procedural systems failed to support workers conducting their work safely and effectively. There is currently a dearth of systematic inquiry regarding the procedure development process. A key element of the procedure development process is writers' guide, which dictates how these procedures should be developed, written, reviewed and managed. The current effort collected 16 writers' guides across various industries such as chemical, oil and gas, nuclear, and energy. Different components of these writers' guides were identified, summarized, and later categorized according to a newly developed writers' guide framework. The framework uses four phases of the procedure life cycle and five sections for procedure content. The analysis showed that industry practices primarily focus on general goals of the procedure, writing style, and review process. Many important components of the procedure, such as process hazard information, execution challenges, and training requirements were not addressed adequately. Of the 41 components, there were only 3 that 80% of the writers' guides contained suggesting little consensus about the content. The proposed writers' guide framework organizes all components including low frequency of appearance ones in different phases of procedure life cycle. The significance of the current procedure writers' guide framework is that it not only produces a structure for a comprehensive writers’ guide but also opens an opportunity for future improvement in current procedure writing practices.     

Systematic packaging design tools integrating functional and environmental consequences on product life cycle: Case studies on laundry detergent and milk

This study presents systematic packaging design tools integrating functional and environmental consequences on product life cycle. To design packaging for sustainability, the trade-offs between functional and environmental aspects of packaging throughout the product life cycle should be considered. However, it is difficult for packaging designers to understand the overall trade-offs because the extent of the design consequences on the entire life cycle of packaging and its contents is unclear. We developed two tools for packaging design: the Life Cycle Association Matrix (LCAM) and the Function Network Diagram (FND). The following three steps, based on literature reviews and interviews with industrial experts, were applied. Firstly, we listed the product functions and design variables related to the functions as the attributes allocated to the product life cycle. Secondly, the attributes were connected appropriately based on causal relationships. Lastly, we identified the factors to support decision making in the packaging design procedure. As a result, the LCAM depicts the design consequences on the life cycle, and the FND determines the stakeholders affected by the design consequences. Two case studies were demonstrated to analyze the trade-offs by using our tools. In the case studies, a liquid laundry detergent bottle and a milk carton were redesigned. The tools identified the design consequences and stakeholders affected by the redesign of the usability and protective function for the detergent and milk cases, respectively. The results showed the significance of understanding the design consequences on the product life cycle by integrating the functional and environmental aspects.     

基于二元水循环的水量-水质-水效联合调控模型开发与应用

为将我国最严格水资源管理制度的实践与二元水循环理论相结合，提高“三条红线”控制指标的科学性与合理性，本文以SWAT模型为基础，通过改进子流域划分方法、添加经济社会模块和人工用水模块，对其人工侧支循环模拟进行了系统的完善，开发了基于SWAT的水量-水质-水效联合调控模型SWAT_WAQER。以广西南流江流域为例，从国民经济用水量、河道径流与水质等方面对模型进行校验，并在此基础上划分了2030年“三条红线”控制指标。结果表明：该模型性能良好，能够用于不同节水情景下的国民经济用水量、污染物排放量、水功能区水质达标结果分析，可以作为科学制定“三条红线”控制指标的有力支撑工具。     

Remote Steering of Self‐Propelling Microcircuits by Modulated Electric Field

The principles and design of “active” self‐propelling particles that can convert energy, move directionally on their own, and perform a certain function is an emerging multidisciplinary research field, with high potential for future technologies. A simple and effective technique is presented for on‐demand steering of self‐propelling microdiodes that move electroosmotically on water surface, while supplied with energy by an external alternating (AC) field. It is demonstrated how one can control remotely the direction of diode locomotion by electronically modifying the applied AC signal. The swimming diodes change their direction of motion when a wave asymmetry (equivalent to a DC offset) is introduced into the signal. The data analysis shows that the ability to control and reverse the direction of motion is a result of the electrostatic torque between the asymmetrically polarized diodes and the ionic charges redistributed in the vessel. This novel principle of electrical signal‐coded steering of active functional devices, such as diodes and microcircuits, can find applications in motile sensors, MEMs, and microrobotics.     

Regenerated air cycle potentials in heat pump applications

Air (reversed Brayton) cycle has been utilized in the area of refrigeration and cryogenics for several decades, but its potentials in heat pump applications were longtime underestimated. In this paper, a thermodynamic model for the regenerated air heat pump cycle with practical compressor, expander and regenerated heat exchanger was developed. Based on the model, the relations between the system performance and the operating parameters were analyzed. The optimal heating COP (coefficient of performance) and the corresponding pressure ratio were derived. Then, air heat pump cycles (regenerated cycle and basic cycle) and vapor-compression heat pump cycles (CO₂ trans-critical cycle and R410A subcritical cycle) were numerically compared. The results indicated that the regenerated air heat pump cycle not only gets the heating capacity in line with the heating load under different operating conditions but also achieves higher COP over trans-critical CO₂ heat pump cycle in applications of large temperature difference.