小型无人直升机纵向和横向动力学的鲁棒反推控制(英文)

研究了阵风情况下悬停飞行模式中的无人直升机的纵向与横向位置的稳定性问题.由于通用的线性模型成功地描述了大多数小型直升机的行为,其被用来设计控制器.基于控制Lyapunov方法,一种递归(反推)设计流程被用来设计纵向和横向动力学的鲁棒控制器.为了比较,我们基于线性二次调节器(LQR)准则设计了另一种控制器.仿真结果表明,所提出的反馈控制器能有效地减弱阵风的影响,在阵风下能够实现纵向和横向位置的快速、准确跟踪.     

Sequential interactions with Sec23 control the direction of vesicle traffic

How the directionality of vesicle traffic is achieved remains an important unanswered question in cell biology. The Sec23p/Sec24p coat complex sorts the fusion machinery (SNAREs) into vesicles as they bud from the endoplasmic reticulum (ER). Vesicle tethering to the Golgi begins when the tethering factor TRAPPI binds to Sec23p. Where the coat is released and how this event relates to membrane fusion is unknown. Here we use a yeast transport assay to demonstrate that an ER-derived vesicle retains its coat until it reaches the Golgi. A Golgi-associated kinase, Hrr25p (CK1δ orthologue), then phosphorylates the Sec23p/Sec24p complex. Coat phosphorylation and dephosphorylation are needed for vesicle fusion and budding, respectively. Additionally, we show that Sec23p interacts in a sequential manner with different binding partners, including TRAPPI and Hrr25p, to ensure the directionality of ER-Golgi traffic and prevent the back-fusion of a COPII vesicle with the ER. These events are conserved in mammalian cells.     

A mutation in APP protects against Alzheimer's disease and age-related cognitive decline

The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-β precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the β-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms.     

Isolation ofiso-butyropyrrothine along with thiolutin and aureothricin from aStreptomyces sp.

Résumé Une nouvelle espèce de Streptomyces (S. pimprina) produit l'iso-butyropyrrothine avec la thiolutine (l'acétopyrrothine), l'aureothricine (la propriopyrrothine) et un antibiotique antifongique du groupe du polyène (heptaène).

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Our thanks are due to Dr.M. J. Thirumalachar for his interest in this work.     

Complete development of human hookworm,Ancylostoma duodenale (Dubini, 1843) in infant rabbits

Summary Establishment of a patent infection ofAncylostoma duodenale in the laboratory host, infant rabbit, is successfully achieved.Acknowledgments. We thank Dr B.B. Gaitondé, Haffkine Institute, for his encouragement and advice in this work.     

Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing

Ataxia-telangiectasia (A-T) results from the loss of ataxia-telangiectasia mutated (Atm) function and is characterized by accelerated telomere loss, genomic instability, progressive neurological degeneration, premature ageing and increased neoplasia incidence. Here we evaluate the functional interaction of Atm and telomeres in vivo. We examined the impact of Atm deficiency as a function of progressive telomere attrition at both the cellular and whole-organism level in mice doubly null for Atm and the telomerase RNA component (Terc). These compound mutants showed increased telomere erosion and genomic instability, yet they experienced a substantial elimination of T-cell lymphomas associated with Atm deficiency. A generalized proliferation defect was evident in all cell types and tissues examined, and this defect extended to tissue stem/progenitor cell compartments, thereby providing a basis for progressive multi-organ system compromise, accelerated ageing and premature death. We show that Atm deficiency and telomere dysfunction act together to impair cellular and whole-organism viability, thus supporting the view that aspects of A-T pathophysiology are linked to the functional state of telomeres and its adverse effects on stem/progenitor cell reserves.     

TRAPPI tethers COPII vesicles by binding the coat subunit Sec23

The budding of endoplasmic reticulum (ER)-derived vesicles is dependent on the COPII coat complex. Coat assembly is initiated when Sar1-GTP recruits the cargo adaptor complex, Sec23/Sec24, by binding to its GTPase-activating protein (GAP) Sec23 (ref. 2). This leads to the capture of transmembrane cargo by Sec24 (refs 3, 4) before the coat is polymerized by the Sec13/Sec31 complex. The initial interaction of a vesicle with its target membrane is mediated by tethers. We report here that in yeast and mammalian cells the tethering complex TRAPPI (ref. 7) binds to the coat subunit Sec23. This event requires the Bet3 subunit. In vitro studies demonstrate that the interaction between Sec23 and Bet3 targets TRAPPI to COPII vesicles to mediate vesicle tethering. We propose that the binding of TRAPPI to Sec23 marks a coated vesicle for fusion with another COPII vesicle or the Golgi apparatus. An implication of these findings is that the intracellular destination of a transport vesicle may be determined in part by its coat and its associated cargo.     

On the viability of the No Alternatives Argument

If we cannot directly empirically test the claims of a particular scientific theory directly, then it would be nice to have some other criteria with which to assess its viability. In his 2013 book, String Theory and the Scientific Method, Richard Dawid aims to develop such criteria, with an eye to vindicating research programmess in disciplines where direct empirical data is scant or non-existent. In an accompanying paper, Dawid, Hartmann and Sprenger formalise Dawid's so-called ‘No Alternatives Argument’ (NAA) using a generalised Bayesian framework, as a first step towards formalising Dawid's entire research programme (which itself relies on two further arguments). In this paper, I argue that the formalisation of the NAA cannot play the central role in Dawid's programme as intended. This is based on the observation that not all confirmation is non-negligible confirmation. For Dawid's programme to be useful, it must demonstrate the viability not just of non-empirical theory confirmation, but of non-negligible non-empirical theory confirmation. I argue that Dawid et al.‘s appeal to Bayesian confirmation theory to formalise his NAA cannot guarantee non-negligible confirmation. As a result, I conclude that if Dawid's overall project is to succeed, it must do so without the NAA formalised in this way.