Properties of Non-Aminoglycoside Compounds Used to Stimulate Translational Readthrough of PTC Mutations in Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a rare disease with autosomal recessive inheritance, caused mostly by bi-allelic gene mutations that impair motile cilia structure and function. Currently, there are no causal treatments for PCD. In many disease models, translational readthrough of premature termination codons (PTC-readthrough) induced by aminoglycosides has been proposed as an effective way of restoring functional protein expression and reducing disease symptoms. However, variable outcomes of pre-clinical trials and toxicity associated with long-term use of aminoglycosides prompt the search for other compounds that might overcome these problems. Because a high proportion of PCD-causing variants are nonsense mutations, readthrough therapies are an attractive option. We tested a group of chemical compounds with known PTC-readthrough potential (ataluren, azithromycin, tylosin, amlexanox, and the experimental compound TC007), collectively referred to as non-aminoglycosides (NAGs). We investigated their PTC-readthrough efficiency in six PTC mutations found in Polish PCD patients, in the context of cell and cilia health, and in comparison to the previously tested aminoglycosides. The NAGs did not compromise the viability of the primary nasal respiratory epithelial cells, and the ciliary beat frequency was retained, similar to what was observed for gentamicin. In HEK293 cells transfected with six PTC-containing inserts, the tested compounds stimulated PTC-readthrough but with lower efficiency than aminoglycosides. The study allowed us to select compounds with minimal negative impact on cell viability and function but still the potential to induce PTC-readthrough.     

爆炸荷载下高耸建筑物过早断裂的数值模拟

爆破拆除高耸建筑物时,爆破切口的爆炸荷载必然产生爆破震动,但有关拟爆物自身震动危害的研究较少,一般以经验来估计爆破震动的影响。采用数值模拟,通过分析爆炸荷载引起的拟爆烟囱上部结构的动力响应来研究爆破震动对过早断裂的影响。结合现场爆破观测的结果,其结论是爆破切口产生爆炸荷载对上部结构的断裂有相当影响,是筒体过早断裂及反向倾转的主要原因,爆炸荷载作用下,烟囱简体高度的55%～75%范围内是断裂危险区,对风化严重等强度低的砖烟囱进行爆破拆除时,尤其应控制单响起爆药量与起爆的间隔时间。     

沥青路面早期损坏的原因分析及防治

针对沥青路面出现的诸多病害，从原材料、施工控制、养护管理三方面分析了沥青路面出现早期损坏的原因，介绍了其防治措施，以保证沥青路面的正常使用，减少损坏现象。     

穿甲弹异物阻滞膛炸机理数值仿真分析

以某穿甲弹近炮口处膛炸故障为背景,针对膛内存在异物时弹体和身管动态响应进行数值仿真,探讨膛炸机理并为故障分析与归零提供依据和参考。设定了两种典型异物阻滞形式：一是 异物阻滞造成弹体速度急剧下降或卡膛;二是弹体直接高速冲击膛内沙土类异物。采用有限元分析AUTODYN软件进行了多种不同工况数值计算,得到了弹体速度急剧下降时弹底燃气流场压力特征、身管变形与破裂形态,以及弹体高速冲击沙土类异物时结构动态响应、身管变形与破裂形态。研究结果表明：弹体膛内突然受阻和速度急剧下降,导致底部燃气中形成激波和局部高压区,局部高压区的存在可造成膛炸;弹体膛内近炮口处高速冲击沙土,身管受到复杂的强动载荷作用并可造成膛炸;数值仿真结果与实际故障情况相吻合并得到了故障复现试验的验证。     

On designing an unaided authentication service with threat detection and leakage control for defeating opportunistic adversaries

Unaided authentication services provide the flexibility to login without being dependent on any additional device. The power of recording attack resilient unaided authentication services (RARUAS) is undeniable as, in some aspects, they are even capable of offering better security than the biometric based authentication systems. However, high login complexity of these RARUAS makes them far from usable in practice. The adopted information leakage control strategies have often been identified as the primary cause behind such high login complexities. Though recent proposals havemade some significant efforts in designing a usable RARUAS by reducing its login complexity, most of them have failed to achieve the desired usability standard. In this paper, we have introduced a new notion of controlling the information leakage rate. By maintaining a good security standard, the introduced idea helps to reduce the login complexity of our proposed mechanism − named as Textual-Graphical Password-based Mechanism or TGPM, by a significant extent. Along with resisting the recording attack, TGPM also achieves a remarkable property of threat detection. To the best of our knowledge, TGPM is the first RARUAS, which can both prevent and detect the activities of the opportunistic recording attackers who can record the complete login activity of a genuine user for a few login sessions. Our study reveals that TGPM assures much higher session resiliency compared to the existing authentication services, having the same or even higher login complexities. Moreover, TGPM stores the password information in a distributed way and thus restricts the adversaries to learn the complete secret from a single compromised server. A thorough theoretical analysis has been performed to prove the strength of our proposal from both the security and usability perspectives. We have also conducted an experimental study to support the theoretical argument made on the usability standard of TGPM.     

一种改进的自适应进化粒子群优化算法

针对粒子群优化算法容易陷入局部极值点以及进化后期收敛慢和优化精度较差等缺点,提出一种改进的自适应进化算法.该算法引入信息扩散函数,根据不同粒子的位置及对应适应值与当前群体最佳位置和最佳适应值的关系,控制粒子变尺度向群体当前最佳位置移动;基于多样性反馈机制动态调节惯性权值和控制粒子群的微变异.通过复杂基准函数的仿真优化结果表明,改进算法具有抑制早熟、收敛速度快、求解精度高的特点.     

Research status of key techniques for shock-induced combustion ramjet(shcramjet) engine

As one of the most promising propulsion systems in the future,shock-induced combustion ramjet engine can remedy the disadvantages in the integrated design of scramjet engine and airframe.It can shorten the length of the combustor,lighten the structure weight of the engine and keep better performance in a broad range of flight Mach number.The elementary principle of shock-induced combustion ramjet engine is introduced.The key technologies of this kind of propulsion system are described,while their research s...     

Premature termination in couple therapy with veterans: Definitions and prediction of long-term outcomes.

Premature termination (PT) has been identified as widespread in individual, family, and couple therapy. Unfortunately, research on PT utilizes numerous definitions of PT without providing guidance on which definition may be most clinically useful. The current study investigated seven definitions of PT (three based on therapist ratings and four based on quantitative measures) utilizing a sample of 177 couples seeking treatment at two Department of Veterans Affairs medical centers. Results indicated that PT occurred in 50–80% of couples; however, agreement between the definitions of PT was generally only in the slight to fair range, making it difficult to determine whether a particular couple was ready to terminate treatment. Additionally, many commonly used definitions of PT were unrelated to level or maintenance of relationship functioning following treatment. In contrast, two definitions of PT (ending treatment in the distressed range and therapist-rated likelihood of future unhappiness) significantly predicted larger decreases in relationship satisfaction during the 18 months following therapy, as well as lower levels of satisfaction and relationship stability 18 months after termination. Additionally, long-term relationship functioning was especially poor when both these definitions of PT were met, suggesting that both qualitative and quantitative definitions should inform decisions about termination in couple therapy. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

沥青路面施工技术浅谈

结合沥青路面的广泛应用，分析了沥青路面早期损害形成的原因，提出了沥青路面施工要领，阐述了沥青路面的技术研究和创新前景，以提高沥青路面的质量，延长沥青路面的使用周期，从而提高投资效益。     

基于经济负荷分配的混沌迭代粒子群算法

为高效求解复杂的非凸、非线性电力系统经济负荷分配问题,提出了一种混沌迭代粒子群算法：粒子群算法的全局搜索能力很强,但易陷入局部最优,混沌的遍历性特性可有效抑制早熟现象。将最优迭代因子引入粒子群算法,对经粒子群算法搜索后的先验解进行基于一种新 Ｔｅｎｔ映射的混沌变异,并改进算法的迭代策略,以平衡粒子的全局和局部性搜索,避免了早熟收敛。通过 ６机组、１５机组的仿真试验,以及同其他算法仿真结果的比较,验证了本算法良好的收敛性和寻优性。