Simulation and uniform design-based automatic generation of risk scenarios

This paper presents a methodology for automatically generating risk scenarios for dynamic reliability applications in which some dynamic characteristics(e.g.,the order,timing and magnitude of events,the value of relevant process parameters and initial conditions) have a significant influence on the evolution of the system.The main idea of the methodology is:(i) making the system model "express itself" through simulation by having the model driven by an elaborated simulation engine;(ii) exploiting uniform design to pick out a small subset of representative design points from the space of relevant dynamic characteristics;(iii) for each selected design point,employing a depth-first systematic exploration strategy to cover all possible scenario branches at each branch point.A highly dynamic example adapted from the literature(a chemical batch reactor) is studied to test the effectiveness of the proposed methodology.     

Aerodynamic force generation of an insect-inspired flapper actuated by a compressed unimorph actuator

We examined experimentally the flapping performance in terms of aerodynamic force generation of an insect-inspired flapper actuated by both of original LIPCA and compressed LIPCA. Flapping tests for two artificial wing shapes of horse botfly and hawk moth were conducted at the wing rotation angle of 60° and a flapping frequency range from 6 Hz to 12 Hz to find the optimum flapping frequency and to investigate the effect of compressed LIPCA and wing shape on the force generation. Flapping tests in the vacuum were also undertaken to measure the induced inertia force. The aerodynamic force was calculated by subtracting the inertia force from the total force measured in the air. It was found that the average inertia force was relatively small when compared with the average total force. The use of the compressed LIPCA could significantly improve the flapping angle of the flapper from 110° to 130° （18.2% increase） resulting in 24.5% increase in the average aerodynamic force. It was also found that flapper with hawk moth wings could produce larger force than the flapper with horse botfly wings.     

Optimum ordering policy for preventive age replacement

Most of the spare ordering policies treated up to now have assumed that preventive and corrective replacement costs are equal, which implies in essential that there is no significant need for preventive replacement. This paper presents an ordering policy for preventive age replacement with minimal repair. Introducing the replacement, repair, inventory holding and shortage costs, the expected cost rate is derived. A procedure to determine jointly the ordering time for a spare and the preventive replacement time for the operating unit so as to minimize the expected cost rate is proposed. To explain the ordering policy and the optimization procedure, a numerical example is also included.     

Misrepresentation in Context

We can witness the recent surge of interest in the interaction between cognitive science, philosophy of science, and aesthetics on the problem of representation. This naturally leads us to rethinking the achievements of Goodman’s monumental book Languages of Art. For, there is no doubt that no one else contributed more than Goodman to throw a light on the cognitive function of art. Ironically, it could be also Goodman who has been the stumbling block for a unified theory of representation. In this paper, I shall contrast the ways how differently misrepresentation has been treated in cognitive science, aesthetics, and philosophy of science. And I shall show that it is Goodman’s unnecessary separation of resemblance and representation in art that made such a difference. As a conclusion, I will indicate some of the most promising projects toward the unified theory of representation the revolt against Goodman’s rejection of resemblance theories might promise to us.     

The Lkb1 metabolic sensor maintains haematopoietic stem cell survival

Haematopoietic stem cells (HSCs) can convert between growth states that have marked differences in bioenergetic needs. Although often quiescent in adults, these cells become proliferative upon physiological demand. Balancing HSC energetics in response to nutrient availability and growth state is poorly understood, yet essential for the dynamism of the haematopoietic system. Here we show that the Lkb1 tumour suppressor is critical for the maintenance of energy homeostasis in haematopoietic cells. Lkb1 inactivation in adult mice causes loss of HSC quiescence followed by rapid depletion of all haematopoietic subpopulations. Lkb1-deficient bone marrow cells exhibit mitochondrial defects, alterations in lipid and nucleotide metabolism, and depletion of cellular ATP. The haematopoietic effects are largely independent of Lkb1 regulation of AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling. Instead, these data define a central role for Lkb1 in restricting HSC entry into cell cycle and in broadly maintaining energy homeostasis in haematopoietic cells through a novel metabolic checkpoint.     

Calmodulin interacts with MLO protein to regulate defence against mildew in barley

In plants, defence against specific isolates of a pathogen can be triggered by the presence of a corresponding race-specific resistance gene, whereas resistance of a more broad-spectrum nature can result from recessive, presumably loss-of-regulatory-function, mutations. An example of the latter are mlo mutations in barley, which have been successful in agriculture for the control of powdery mildew fungus (Blumeria graminis f. sp. hordei; Bgh). MLO protein resides in the plasma membrane, has seven transmembrane domains, and is the prototype of a sequence-diversified family unique to plants, reminiscent of the seven-transmembrane receptors in fungi and animals. In animals, these are known as G-protein-coupled receptors and exist in three main families, lacking sequence similarity, that are thought to be an example of molecular convergence. MLO seems to function independently of heterotrimeric G proteins. We have identified a domain in MLO that mediates a Ca2+-dependent interaction with calmodulin in vitro. Loss of calmodulin binding halves the ability of MLO to negatively regulate defence against powdery mildew in vivo. We propose a sensor role for MLO in the modulation of defence reactions.     

DNMT1 and DNMT3b cooperate to silence genes in human cancer cells

Inactivation of tumour suppressor genes is central to the development of all common forms of human cancer. This inactivation often results from epigenetic silencing associated with hypermethylation rather than intragenic mutations. In human cells, the mechanisms underlying locus-specific or global methylation patterns remain unclear. The prototypic DNA methyltransferase, Dnmt1, accounts for most methylation in mouse cells, but human cancer cells lacking DNMT1 retain significant genomic methylation and associated gene silencing. We disrupted the human DNMT3b gene in a colorectal cancer cell line. This deletion reduced global DNA methylation by less than 3%. Surprisingly, however, genetic disruption of both DNMT1 and DNMT3b nearly eliminated methyltransferase activity, and reduced genomic DNA methylation by greater than 95%. These marked changes resulted in demethylation of repeated sequences, loss of insulin-like growth factor II (IGF2) imprinting, abrogation of silencing of the tumour suppressor gene p16INK4a, and growth suppression. Here we demonstrate that two enzymes cooperatively maintain DNA methylation and gene silencing in human cancer cells, and provide compelling evidence that such methylation is essential for optimal neoplastic proliferation.