Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Сберегательное поведение в контексте исследования белорусской деловой культуры

Материалы X Международной научной конференции 25–26 мая 2017 г

Increased therapeutic potential of an experimental anti-mitotic inhibitor SB715992 by genistein in PC-3 human prostate cancer cell line

BACKGROUND: Kinesin spindle proteins (KSP) are motor proteins that play an essential role in mitotic spindle formation. HsEg5, a KSP, is responsible for the formation of the bipolar spindle, which is critical for proper cell division during mitosis. The function of HsEg5 provides a novel target for the manipulation of the cell cycle and the induction of apoptosis. SB715992, an experimental KSP inhibitor, has been shown to perturb bipolar spindle formation, thus making it an excellent candidate for anti-cancer agent. Our major objective was a) to investigate the cell growth inhibitory effects of SB715992 on PC-3 human prostate cancer cell line, b) to investigate whether the growth inhibitory effects of SB715992 could be enhanced when combined with genistein, a naturally occurring isoflavone and, c) to determine gene expression profile to establish molecular mechanism of action of SB715992. METHODS: PC-3 cells were treated with varying concentration of SB715992, 30 μM of genistein, and SB715992 plus 30 μM of genistein. After treatments, PC-3 cells were assayed for cell proliferation, induction of apoptosis, and alteration in gene and protein expression using cell inhibition assay, apoptosis assay, microarray analysis, real-time RT-PCR, and Western Blot analysis. RESULTS: SB715992 inhibited cell proliferation and induced apoptosis in PC-3 cells. SB715992 was found to regulate the expression of genes related to the control of cell proliferation, cell cycle, cell signaling pathways, and apoptosis. In addition, our results showed that combination treatment with SB715992 and genistein caused significantly greater cell growth inhibition and induction of apoptosis compared to the effects of either agent alone. CONCLUSION: Our results clearly show that SB715992 is a potent anti-tumor agent whose therapeutic effects could be enhanced by genistein. Hence, we believe that SB715992 could be a novel agent for the treatment of prostate cancer with greater success when combined with a non-toxic natural agent like genistein

Survival of patients with metastatic breast cancer: twenty-year data from two SEER registries

BACKGROUND: Many researchers are interested to know if there are any improvements in recent treatment results for metastatic breast cancer in the community, especially for 10- or 15-year survival. METHODS: Between 1981 and 1985, 782 and 580 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries of the Surveillance, Epidemiology, and End Results (SEER) database. The lognormal statistical method to estimate survival was retrospectively validated since the 15-year cause-specific survival rates could be calculated using the standard life-table actuarial method. Estimated rates were compared to the actuarial data available in 2000. Between 1991 and 1995, further 752 and 632 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries. The data were analyzed to estimate the 15-year cause-specific survival rates before the year 2005. RESULTS: The 5-year period (1981–1985) was chosen, and patients were followed as a cohort for an additional 3 years. The estimated 15-year cause-specific survival rates were 7.1% (95% confidence interval, CI, 1.8–12.4) and 9.1% (95% CI, 3.8–14.4) by the lognormal model for the two registries of Connecticut and San Francisco-Oakland respectively. Since the SEER database provides follow-up information to the end of the year 2000, actuarial calculation can be performed to confirm (validate) the estimation. The Kaplan-Meier calculation for the 15-year cause-specific survival rates were 8.3% (95% CI, 5.8–10.8) and 7.0% (95% CI, 4.3–9.7) respectively. Using the 1991–1995 5-year period cohort and followed for an additional 3 years, the 15-year cause-specific survival rates were estimated to be 9.1% (95% CI, 3.8–14.4) and 14.7% (95% CI, 9.8–19.6) for the two registries of Connecticut and San Francisco-Oakland respectively. CONCLUSIONS: For the period 1981–1985, the 15-year cause-specific survival for the Connecticut and the San Francisco-Oakland registries were comparable. For the period 1991–1995, there was not much change in survival for the Connecticut registry patients, but there was an improvement in survival for the San Francisco-Oakland registry patients

Search of Dark Matter Annihilation in the Galactic Centre using the ANTARES Neutrino Telescope

A search for high-energy neutrinos coming from the direction of the GalacticCentre is performed using the data recorded by the ANTARES neutrino telescopefrom 2007 to 2012. The event selection criteria are chosen to maximise thesensitivity to possible signals produced by the self-annihilation of weaklyinteracting massive particles accumulated around the centre of the Milky Waywith respect to the atmospheric background. After data unblinding, the numberof neutrinos observed in the line of sight of the Galactic Centre is found tobe compatible with background expectations. The 90% C.L. upper limits in termsof the neutrino+anti-neutrino flux, $\rm \Phi_{\nu_{\mu}+\bar{\nu}_\mu}$, andthe velocity averaged annihilation cross-section, $\rm$, arederived for the WIMP self-annihilation channels into \rmb\bar{b},W^{+}W^{-},\tau^{+}\tau^{-},\mu^{+}\mu^{-},\nu\bar{\nu}. The ANTARESlimits for $\rm$ are shown to be the most stringent for aneutrino telescope over the WIMP masses $\rm 25\,GeV < M_{WIMP} < 10\,TeV$

Status of Turbulence Modeling for Hypersonic Propulsion Flowpaths

This report provides an assessment of current turbulent flow calculation methods for hypersonic propulsion flowpaths, particularly the scramjet engine. Emphasis is placed on Reynolds-averaged Navier-Stokes (RANS) methods, but some discussion of newer meth- ods such as Large Eddy Simulation (LES) is also provided. The report is organized by considering technical issues throughout the scramjet-powered vehicle flowpath including laminar-to-turbulent boundary layer transition, shock wave / turbulent boundary layer interactions, scalar transport modeling (specifically the significance of turbulent Prandtl and Schmidt numbers) and compressible mixing. Unit problems are primarily used to conduct the assessment. In the combustor, results from calculations of a direct connect supersonic combustion experiment are also used to address the effects of turbulence model selection and in particular settings for the turbulent Prandtl and Schmidt numbers. It is concluded that RANS turbulence modeling shortfalls are still a major limitation to the accuracy of hypersonic propulsion simulations, whether considering individual components or an overall system. Newer methods such as LES-based techniques may be promising, but are not yet at a maturity to be used routinely by the hypersonic propulsion community. The need for fundamental experiments to provide data for turbulence model development and validation is discussed

Observation of charmless hadronic B decays

Four candidates for charmless hadronic B decay are observed in a data sample of four million hadronic Z decays recorded by the ALEPH detector at LEP. The probability that these events come from background sources is estimated to be less than 10(-6). The average branching of weakly decaying B hadrons (a mixture of B-d(0), B-s(0) and Lambda(b) weighted by their production The average branching ratio of weakly decaying B hadrons (a mixture of B-d(0) cross sections and lifetimes, here denoted B) into two long-lived charged hadrons (pions, kaons or protons) is measured to be Br(B-->h(+)h(-))=(1.7(-0.7)(+1.0)+/-0.2)x10(-5). The relative branching fraction Br(B-d(s)(0)-->pi(+)pi(-)(K-))/Br(B-d(s)(0)-->h(+)h(-)) is measured to be 1.0(-0.3-0.1)(+0.0+0.0). In addition, branching ratio upper limits are obtained for a variety of exclusive charmless hadronic two-body decays of B hadrons

Supernova Neutrino Burst Detection with the Deep Underground Neutrino Experiment

The Deep Underground Neutrino Experiment (DUNE), a 40-kton underground liquid argon time projection chamber experiment, will be sensitive to the electron-neutrino flavor component of the burst of neutrinos expected from the next Galactic core-collapse supernova. Such an observation will bring unique insight into the astrophysics of core collapse as well as into the properties of neutrinos. The general capabilities of DUNE for neutrino detection in the relevant few- to few-tens-of-MeV neutrino energy range will be described. As an example, DUNE's ability to constrain the ν_e spectral parameters of the neutrino burst will be considered

Four-fermion production in e+e−e^+e^- collisions at centre-of-mass energies of 130 and 136 GeV

Four-fermion events have been selected in a data sample of 5.8 pb−1 collected with the aleph detector at centre-of-mass energies of 130 and 136 GeV. The final states , ℓ+ℓ−ℓ+ℓ−, , and have been examined. Five events are observed in the data, in agreement with the Standard Model predictions of 6.67±0.38 events from four-fermion processes and 0.14−0.05+0.19 from background processes