Stochastic process model for timber-concrete composite beam deterioration

The aim of this paper is to present a new stochastic process model that will capture the true nature of deterioration of timber-concrete composite beams. Composite elements such as timber-concrete composite sections are designed to take advantage of compatibility of materials under sustained loading. Applied sustained load on timber-concrete composite structures causes gradual increase of deformation and deflection. In particular for timber-concrete composite beams, component materials will deteriorate at different pace over the life-cycle. In order to enable efficient management of structures in terms of required maintenance, repair and/or replacement, it is essential to be able to capture the uncertain nature of the deterioration process. We focus on modeling the deterioration of mid-span deflection of the timber-concrete composite beam over long term under sustained load. As the increasing deflection of the timber-concrete composite beam over time is generally uncertain and non-decreasing, it can best be regarded as a continuous gamma process. Examples of continuous gamma process representation have been included

Gamma process model for timber-concrete composite beam deterioration prediction

This paper presents the application of the advanced probabilistic slope stability model with precipitation effects (APSMP) developed to assess the performance of small homogeneous earthfill embankment dam slopes, when exposed to future seasonal precipitation scenarios. Here, the UKs latest probabilistic climate model known as UKCP09 is applied. To reflect the critical conditions conducive to slope failure, a benchmark has been developed to identify the change, if any, in the risk classification of the slope’s performance level due to precipitation. Thus, enabling the reassessment of the dam’s risk classification, as categorized by the Flood and Water Management Act 2010. Such an approach could therefore be well placed to support and enhance the decision making process, its impact on the public, especially in relation to future climate effects

SAM68 is required for regulation of Pumilio by the NORAD long noncoding RNA

The number of known long noncoding RNA (lncRNA) functions is rapidly growing, but how those functions are encoded in their sequence and structure remains poorly understood. NORAD (noncoding RNA activated by DNA damage) is a recently characterized, abundant, and highly conserved lncRNA that is required for proper mitotic divisions in human cells. NORAD acts in the cytoplasm and antagonizes repressors from the Pumilio family that bind at least 17 sites spread through 12 repetitive units in NORAD sequence. Here we study conserved sequences in NORAD repeats, identify additional interacting partners, and characterize the interaction between NORAD and the RNA-binding protein SAM68 (KHDRBS1), which is required for NORAD function in antagonizing Pumilio. These interactions provide a paradigm for how repeated elements in a lncRNA facilitate function.</jats:p

Autonomous object harvesting using synchronized optoelectronic microrobots

Optoelectronic tweezer-driven microrobots (OETdMs) are a versatile micromanipulation technology based on the application of light induced dielectrophoresis to move small dielectric structures (microrobots) across a photoconductive substrate. The microrobots in turn can be used to exert forces on secondary objects and carry out a wide range of micromanipulation operations, including collecting, transporting and depositing microscopic cargos. In contrast to alternative (direct) micromanipulation techniques, OETdMs are relatively gentle, making them particularly well suited to interacting with sensitive objects such as biological cells. However, at present such systems are used exclusively under manual control by a human operator. This limits the capacity for simultaneous control of multiple microrobots, reducing both experimental throughput and the possibility of cooperative multi-robot operations. In this article, we describe an approach to automated targeting and path planning to enable open-loop control of multiple microrobots. We demonstrate the performance of the method in practice, using microrobots to simultaneously collect, transport and deposit silica microspheres. Using computational simulations based on real microscopic image data, we investigate the capacity of microrobots to collect target cells from within a dissociated tissue culture. Our results indicate the feasibility of using OETdMs to autonomously carry out micromanipulation tasks within complex, unstructured environments

Exclusion statistics,operator algebras and Fock space representations

We study exclusion statistics within the second quantized approach. We consider operator algebras with positive definite Fock space and restrict them in a such a way that certain state vectors in Fock space are forbidden ab initio.We describe three characteristic examples of such exclusion, namely exclusion on the base space which is characterized by states with specific constraint on quantum numbers belonging to base space M (e.g. Calogero-Sutherland type of exclusion statistics), exclusion in the single-oscillator Fock space, where some states in single oscillator Fock space are forbidden (e.g. the Gentile realization of exclusion statistics) and a combination of these two exclusions (e.g. Green's realization of para-Fermi statistics). For these types of exclusions we discuss extended Haldane statistics parameters g, recently introduced by two of us in Mod.Phys.Lett.A 11, 3081 (1996), and associated counting rules. Within these three types of exclusions in Fock space the original Haldane exclusion statistics cannot be realized.Comment: Latex,31 pages,no figures,to appear in J.Phys.A : Math.Ge

Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions.

Long noncoding RNAs (lncRNAs) regulate gene expression via their RNA product or through transcriptional interference, yet a strategy to differentiate these two processes is lacking. To address this, we used multiple small interfering RNAs (siRNAs) to silence GNG12-AS1, a nuclear lncRNA transcribed in an antisense orientation to the tumour-suppressor DIRAS3. Here we show that while most siRNAs silence GNG12-AS1 post-transcriptionally, siRNA complementary to exon 1 of GNG12-AS1 suppresses its transcription by recruiting Argonaute 2 and inhibiting RNA polymerase II binding. Transcriptional, but not post-transcriptional, silencing of GNG12-AS1 causes concomitant upregulation of DIRAS3, indicating a function in transcriptional interference. This change in DIRAS3 expression is sufficient to impair cell cycle progression. In addition, the reduction in GNG12-AS1 transcripts alters MET signalling and cell migration, but these are independent of DIRAS3. Thus, differential siRNA targeting of a lncRNA allows dissection of the functions related to the process and products of its transcription.The authors acknowledge all the members of Murrell, Rinn, Odom and Gergely laboratory as well as Massimiliano di Pietro, Klaas Mulder, Anna Git, Jason Carroll in Cambridge and Laurence Hurst (University of Bath) for reading and providing helpful comments on the manuscript. We also thank the Genomics, Microscopy and Bioinformatics core facilities at the Cambridge Institute for support, Christina Ernst for thumbnail image design, Ezgi Hacisuleyman for the design of the negative control vector, Cole Trapnell and David Hendrickson for providing us with lincExpress vector, Arjun Raj with the RNA FISH and Alaisdair Russell with the lentiviral work. This research was supported by The University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited. The authors have no conflicting financial interests.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1040

Residual γH2AX foci as an indication of lethal DNA lesions

<p>Abstract</p> <p>Background</p> <p>Evidence suggests that tumor cells exposed to some DNA damaging agents are more likely to die if they retain microscopically visible γH2AX foci that are known to mark sites of double-strand breaks. This appears to be true even after exposure to the alkylating agent MNNG that does not cause direct double-strand breaks but does produce γH2AX foci when damaged DNA undergoes replication.</p> <p>Methods</p> <p>To examine this predictive ability further, SiHa human cervical carcinoma cells were exposed to 8 DNA damaging drugs (camptothecin, cisplatin, doxorubicin, etoposide, hydrogen peroxide, MNNG, temozolomide, and tirapazamine) and the fraction of cells that retained γH2AX foci 24 hours after a 30 or 60 min treatment was compared with the fraction of cells that lost clonogenicity. To determine if cells with residual repair foci are the cells that die, SiHa cervical cancer cells were stably transfected with a RAD51-GFP construct and live cell analysis was used to follow the fate of irradiated cells with RAD51-GFP foci.</p> <p>Results</p> <p>For all drugs regardless of their mechanism of interaction with DNA, close to a 1:1 correlation was observed between clonogenic surviving fraction and the fraction of cells that retained γH2AX foci 24 hours after treatment. Initial studies established that the fraction of cells that retained RAD51 foci after irradiation was similar to the fraction of cells that retained γH2AX foci and subsequently lost clonogenicity. Tracking individual irradiated live cells confirmed that SiHa cells with RAD51-GFP foci 24 hours after irradiation were more likely to die.</p> <p>Conclusion</p> <p>Retention of DNA damage-induced γH2AX foci appears to be indicative of lethal DNA damage so that it may be possible to predict tumor cell killing by a wide variety of DNA damaging agents simply by scoring the fraction of cells that retain γH2AX foci.</p