A Laboratory Excitation Technique to Test Road Bike Vibration Transmission

This paper describes a technique designed to measure the in-situ acceleration signals that will be used to drive a road simulator in the study of road bike vibration transmission in a laboratory setting. To measure the signals, a bike mounted by a cyclist and towed by a motor vehicle is used. A road simulator using actuators driven by a digital signal is described. The impulse response of the bike used to measure road data is convoluted with the road acceleration in order to obtain the required actuator signal. The reproduction capacity of the simulator is evaluated by comparing the frequency content as well as the time statistical parameters of the acceleration signal measurement with road to the acceleration obtained on the simulator. On a granular road with a broadband excitation spectrum, the vertical excitation obtained with the simulator adequately mimics the measured road acceleration. This technique can be used to compare vibration transmission characteristics among different road bikes.The authors gratefully acknowledge financial support from the National Science and Engineering Council of Canada (NSERC) and the participation of Cervélo and Vroomen-White Design

The relative contribution of road bicycle components on vibration induced to the cyclist

Improving comfort in road bicycle design is a paramount concern for cyclists, who are affected by the vibrations caused by constant contact with the road surface. The cycling community has deployed many efforts in the attempt to understand and improve bicycle comfort. However, these attempts have been focused on specific components such as the fork, frame and wheels without knowing their relative influence on vibration induced to the bicyclist (VIB). The objective of this paper is to assess the relative contribution of bicycle components on the VIB at the cyclist’s hands and buttocks. A factorial design test comparing the VIB in acceleration, force and power of different bicycle components has already shown that the handlebar and fork are the preponderant components for the VIB measured at the cyclist’s hands. At the buttocks, the preponderant components are the wheels and frame.The authors gratefully acknowledge financial support from the National Science and Engineering Council of Canada (NSERC) and the participation of Cervelo and Vroomen-White Design

Road bike comfort: on the measurement of vibrations induced to cyclist

With ride quality being one of the most sought-after characteristics of a road bicycle by customers as well as by bicycle manufacturers, the vibrational behaviour of the bicycle/cyclist system has grown into an active field in sport engineering research in recent years. When assessing bicycle transmissibility and ride comfort, it is important to control test conditions to obtain repeatable load and acceleration measurements at the cyclist’s contact points with the bicycle. Surprisingly, however, this consideration has not yet been specifically addressed in the literature. The aim of this paper is a first effort to investigate the effect of a selected set of test conditions on the measurement of vibration induced to the cyclist by a road bicycle. Our results showed that all the test conditions selected had a significant effect on the level of vibration induced to the cyclist.The authors gratefully acknowledge financial support from the National Science and Engineering Council of Canada (NSERC) and the participation of Cervélo and Vroomen-White Design

BLM and RMI1 alleviate RPA inhibition of topoIIIα decatenase activity

RPA is a single-stranded DNA binding protein that physically associates with the BLM complex. RPA stimulates BLM helicase activity as well as the double Holliday junction dissolution activity of the BLM-topoisomerase IIIα complex. We investigated the effect of RPA on the ssDNA decatenase activity of topoisomerase IIIα. We found that RPA and other ssDNA binding proteins inhibit decatenation by topoisomerase IIIα. Complex formation between BLM, TopoIIIα, and RMI1 ablates inhibition of decatenation by ssDNA binding proteins. Together, these data indicate that inhibition by RPA does not involve species-specific interactions between RPA and BLM-TopoIIIα-RMI1, which contrasts with RPA modulation of double Holliday junction dissolution. We propose that topoisomerase IIIα and RPA compete to bind to single-stranded regions of catenanes. Interactions with BLM and RMI1 enhance toposiomerase IIIα activity, promoting decatenation in the presence of RPA

STK295900, a Dual Inhibitor of Topoisomerase 1 and 2, Induces G<inf>2</inf> Arrest in the Absence of DNA Damage

STK295900, a small synthetic molecule belonging to a class of symmetric bibenzimidazoles, exhibits antiproliferative activity against various human cancer cell lines from different origins. Examining the effect of STK295900 in HeLa cells indicates that it induces G2 phase arrest without invoking DNA damage. Further analysis shows that STK295900 inhibits DNA relaxation that is mediated by topoisomerase 1 (Top 1) and topoisomerase 2 (Top 2) in vitro. In addition, STK295900 also exhibits protective effect against DNA damage induced by camptothecin. However, STK295900 does not affect etoposide-induced DNA damage. Moreover, STK295900 preferentially exerts cytotoxic effect on cancer cell lines while camptothecin, etoposide, and Hoechst 33342 affected both cancer and normal cells. Therefore, STK295900 has a potential to be developed as an anticancer chemotherapeutic agent. © 2013 Kim et al

Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability

Peer reviewedPublisher PD

Coherent and Incoherent Scattering Mechanisms in Air-Filled Permeable Materials

Ultrasonic evaluation of porous materials can take advantage of some very specific acoustic phenomena that occur only in fluid-saturated consolidated solids of continuously connected pore structure. The most interesting feature of acoustic wave propagation in such media is the appearance of a second compressional wave, the so-called slow wave [1,2]. The slow compressional wave represents a relative motion between the fluid and the solid frame. This motion is very sensitive to the kinematic viscosity of the fluid and the dynamic permeability of the porous formation. Certain material properties such as tortuosity, permeability, porosity, and pore size, shape and surface quality are inherently connected to the porous nature of the material and can be evaluated best from the propagation properties of the slow compressional wave.</p

The modulation of topoisomerase I-mediated DNA cleavage and the induction of DNA–topoisomerase I crosslinks by crotonaldehyde-derived DNA adducts

Crotonaldehyde is a representative α,β-unsaturated aldehyde endowed of mutagenic and carcinogenic properties related to its propensity to react with DNA. Cyclic crotonaldehyde-derived deoxyguanosine (CrA-PdG) adducts can undergo ring opening in duplex DNA to yield a highly reactive aldehydic moiety. Here, we demonstrate that site-specifically modified DNA oligonucleotides containing a single CrA-PdG adduct can form crosslinks with topoisomerase I (Top1), both directly and indirectly. Direct covalent complex formation between the CrA-PdG adduct and Top1 is detectable after reduction with sodium cyanoborohydride, which is consistent with the formation of a Schiff base between Top1 and the ring open aldehyde form of the adduct. In addition, we show that the CrA-PdG adduct alters the cleavage and religation activities of Top1. It suppresses Top1 cleavage complexes at the adduct site and induces both reversible and irreversible cleavage complexes adjacent to the CrA-PdG adduct. The formation of stable DNA–Top1 crosslinks and the induction of Top1 cleavage complexes by CrA-PdG are mutually exclusive. Lastly, we found that crotonaldehyde induces the formation of DNA–Top1 complexes in mammalian cells, which suggests a potential relationship between formation of DNA–Top1 crosslinks and the mutagenic and carcinogenic properties of crotonaldehyde

Development of Derivatives of 3, 3′-Diindolylmethane as Potent Leishmania donovani Bi-Subunit Topoisomerase IB Poisons

Background: The development of 3, 39-diindolyl methane (DIM) resistant parasite Leishmania donovani (LdDR50) by adaptation with increasing concentrations of the drug generates random mutations in the large and small subunits of heterodimeric DNA topoisomerase I of Leishmania (LdTOP1LS). Mutation of large subunit of LdTOP1LS at F270L is responsible for resistance to DIM up to 50 mM concentration. Methodology/Principal Findings: In search of compounds that inhibit the growth of the DIM resistant parasite and inhibit the catalytic activity of mutated topoisomerase I (F270L), we have prepared three derivatives of DIM namely DPDIM (2,29diphenyl 3,39-diindolyl methane), DMDIM (2,29-dimethyl 3,39-diindolyl methane) and DMODIM (5,59-dimethoxy 3,39diindolyl methane) from parent compound DIM. All the compounds inhibit the growth of DIM resistant parasites, induce DNA fragmentation and stabilize topo1-DNA cleavable complex with the wild type and mutant enzyme. Conclusion: The results suggest that the three derivatives of DIM can act as promising lead molecules for the generation of new anti-leishmanial agents

Integrated genetic map and genetic analysis of a region associated with root traits on the short arm of rye chromosome 1 in bread wheat

A rye–wheat centric chromosome translocation 1RS.1BL has been widely used in wheat breeding programs around the world. Increased yield of translocation lines was probably a consequence of increased root biomass. In an effort to map loci-controlling root characteristics, homoeologous recombinants of 1RS with 1BS were used to generate a consensus genetic map comprised of 20 phenotypic and molecular markers, with an average spacing of 2.5 cM. Physically, all recombination events were located in the distal 40% of the arms. A total of 68 recombinants was used and recombination breakpoints were aligned and ordered over map intervals with all the markers, integrated together in a genetic map. This approach enabled dissection of genetic components of quantitative traits, such as root traits, present on 1S. To validate our hypothesis, phenotyping of 45-day-old wheat roots was performed in five lines including three recombinants representative of the entire short arm along with bread wheat parents ‘Pavon 76’ and Pavon 1RS.1BL. Individual root characteristics were ranked and the genotypic rank sums were subjected to Quade analysis to compare the overall rooting ability of the genotypes. It appears that the terminal 15% of the rye 1RS arm carries gene(s) for greater rooting ability in wheat