Characterization of a recently synthesized microtubule-targeting compound that disrupts mitotic spindle poles in human cells

We reveal the effects of a new microtubule-destabilizing compound in human cells. C75 has a core thienoisoquinoline scaffold with several functional groups amenable to modification. Previously we found that sub micromolar concentrations of C75 caused cytotoxicity. We also found that C75 inhibited microtubule polymerization and competed with colchicine for tubulin-binding in vitro. However, here we found that the two compounds synergized suggesting differences in their mechanism of action. Indeed, live imaging revealed that C75 causes different spindle phenotypes compared to colchicine. Spindles remained bipolar and collapsed after colchicine treatment, while C75 caused bipolar spindles to become multipolar. Importantly, microtubules rapidly disappeared after C75-treatment, but then grew back unevenly and from multiple poles. The C75 spindle phenotype is reminiscent of phenotypes caused by depletion of ch-TOG, a microtubule polymerase, suggesting that C75 blocks microtubule polymerization in metaphase cells. C75 also caused an increase in the number of spindle poles in paclitaxel-treated cells, and combining low amounts of C75 and paclitaxel caused greater regression of multicellular tumour spheroids compared to each compound on their own. These findings warrant further exploration of C75’s anti-cancer potential.

Exact S-Matrices

The Ising model in a magnetic field is one of the most beautiful examples of an integrable model. This chapter presents its exact S-matrix and the exact spectrum of its excitations, which consist of eight particles of different masses. Similarly, it discusses the exact scattering theory behind the thermal deformation of the tricritical Ising model and the unusual features of the exact S-matrix of the non-unitary Yang–Lee model. Other examples are provided by O(n) invariant models, including the important Sine–Gordon model. It also discusses multiple poles, magnetic deformation, the E 8 Toda theory, bootstrap fusion rules, non-relativistic limits and quantum group symmetry of the Sine–Gordon model.

EXACT LOCAL WHITTLE ESTIMATION IN LONG MEMORY TIME SERIES WITH MULTIPLE POLES

A generalization of the Exact Local Whittle estimator in Shimotsu and Phillips (2005, Annals of Statistics 33, 1890–1933) is proposed for jointly estimating all the memory parameters in general long memory time series that possibly display standard, seasonal, and/or other cyclical strong persistence. Consistency and asymptotic normality are proven for stationary, nonstationary, and noninvertible series, permitting straightforward standard inference of interesting hypotheses such as the existence of unit roots and equality of memory parameters at some or all seasonal frequencies, which can be used as a prior test for the application of seasonal differencing filters. The effects of unknown deterministic terms are also discussed. Finally, the finite sample performance is analyzed in an extensive Monte Carlo exercise and an application to an U.S. Industrial Production index.

Development of Magnetorheological Brake with Tooth-Shaped Disc for Small Size Motorcycle

In this research, a new type of magneto-rheological brake (MRB) is proposed for small size motorcycle. The proposed MRB consists of a rotor with multiple trapezoidal teeth acting at multiple magnetic poles of the brake. In order to generate a magnetic field for controlling braking torque, a magnetic coil is placed on each side-housing of the brake. The inner face of each side-housing also has trapezoidal shape mating with the trapezoidal teeth of the rotor via MRF layer. By applying countercurrents to the coils, a magnetic fluid is generated with some magnetic flux going across the MRF layer (MRF duct) between the rotor teeth and their mating poles on the housing. By using multiple poles with trapezoidal shape, a high braking torque of the brake is expected while the size of the brake is still kept to be compacted. After an introduction about the development of MRBs in automotive engineering, the configuration of the proposed MRB is presented and its braking torque is derived based on Bingham rheological model of MRF. The proposed MRB is then optimally designed based on finite element analysis (FEA). Its optimized MRB is then manufactured and its braking performance is experimentally investigated. The MRB is then installed in a prototype motorcycle and the field test of this prototype motorcycle integrated with the MRB is then conducted.