Novel pharmacological actions of Trequinsin Hydrochloride improve human sperm cell motility and function

Background and purposeAsthenozoospermia is a leading cause of male infertility, but the development of pharmaceuticals to improve sperm motility has been hindered by the lack of effective screening platforms and knowledge of suitable molecular targets. We have demonstrated that a high throughput screening (HTS) strategy in conjunction with established in vitro tests can identify and characterise the action of compounds that improve sperm motility. The study aimed to apply HTS to identify new compounds from a novel small molecule library that increase intracellular calcium, [Ca2+]I, promote human sperm cell motility and systemically determine the mechanism of action. Experimental approach A validated HTS fluorometric [Ca2+]i assay was used to screen an in-house library of compounds. Trequinsin hydrochloride (a phosphodiesterase 3 inhibitor) was selected for detailed molecular (plate reader assays, electrophysiology and cyclic nucleotide measurement) and functional (motility and acrosome reaction) testing in sperm from healthy volunteer donors and, where possible, patients.   Key resultsThe fluorometric analysis identified Trequinsin as an efficacious agonist of [Ca2+]i, although less potent than progesterone (P4). Functionally, Trequinsin significantly increased cell hyperactivation and penetration into viscous medium in all donor sperm samples and cell hyperactivation in 22/25 (88%) patient sperm samples. The Trequinsin-induced [Ca2+]i response was cross-desensitised consistently by prostaglandin E1 but not with P4. Whole-cell patch clamp electrophysiology confirmed that Trequinsin activates CatSper and partially inhibits potassium channel activity. Trequinsin also increases intracellular cGMP.   Conclusion and Implications Trequinsin exhibits a novel pharmacological profile in human sperm and may be a suitable lead compound for the development of new pharmaceuticals to improve patient sperm function and fertilisation potential

Atom probe microscopy of zinc isotopic enrichment in ZnO nanorods

We report on atomic probe microscopy (APM) of isotopically enriched ZnO nanorods that measures the spatial distribution of zinc isotopes in sections of ZnO nanorods for natural abundance natZnO and 64Zn and 66Zn enriched ZnO nanorods. The results demonstrate that APM can accurately quantify isotopic abundances within these nanoscale structures. Therefore the atom probe microscope is a useful tool for characterizing Zn isotopic heterostructures in ZnO. Isotopic heterostructures have been proposed for controlling thermal conductivity and also, combined with neutron transmutation doping, they could be key to a novel technology for producing p-n junctions in ZnO thin films and nanorods

Rotation and Macroturbulence in Metal-Poor Field Red Giant and Red Horizontal Branch Stars

We report the results for rotational velocities, Vrot sin i, and macroturbulence dispersions, ζRT, for 12 metal-poor field red giant branch (RGB) stars and 7 metal-poor field red horizontal branch (RHB) stars. The results are based on Fourier transform

News from the Muon (g-2) Experiment at BNL

The magnetic moment anomaly a_mu = (g_mu - 2) / 2 of the positive muon has been measured at the Brookhaven Alternating Gradient Synchrotron with an uncertainty of 0.7 ppm. The new result, based on data taken in 2000, agrees well with previous measurements. Standard Model evaluations currently differ from the experimental result by 1.6 to 3.0 standard deviations.Comment: Talk presented at RADCOR - Loops and Legs 2002, Kloster Banz, Germany, September 8-13 2002, to be published in Nuclear Physics B (Proc. Suppl.); 5 pages, 3 figure

Study of the B^0 Semileptonic Decay Spectrum at the Upsilon(4S) Resonance

We have made a first measurement of the lepton momentum spectrum in a sample of events enriched in neutral B's through a partial reconstruction of B0 --> D*- l+ nu. This spectrum, measured with 2.38 fb**-1 of data collected at the Upsilon(4S) resonance by the CLEO II detector, is compared directly to the inclusive lepton spectrum from all Upsilon(4S) events in the same data set. These two spectra are consistent with having the same shape above 1.5 GeV/c. From the two spectra and two other CLEO measurements, we obtain the B0 and B+ semileptonic branching fractions, b0 and b+, their ratio, and the production ratio f+-/f00 of B+ and B0 pairs at the Upsilon(4S). We report b+/b0=0.950 (+0.117-0.080) +- 0.091, b0 = (10.78 +- 0.60 +- 0.69)%, and b+ = (10.25 +- 0.57 +- 0.65)%. b+/b0 is equivalent to the ratio of charged to neutral B lifetimes, tau+/tau0.Comment: 14 page, postscript file also available at http://w4.lns.cornell.edu/public/CLN

Observation of the Ξc+\Xi_c^+ Charmed Baryon Decays to Σ+K−π+\Sigma^+ K^-\pi^+, Σ+Kˉ∗0\Sigma^+ \bar{K}^{*0}, and ΛK−π+π+\Lambda K^-\pi^+\pi^+

We have observed two new decay modes of the charmed baryon $\Xi_c^+$ into $\Sigma^+ K^-\pi^+$ and $\Sigma^+ \bar{K}^{*0}$ using data collected with the CLEO II detector. We also present the first measurement of the branching fraction for the previously observed decay mode $\Xi_c^+\to\Lambda K^-\pi^+\pi^+$. The branching fractions for these three modes relative to $\Xi_c^+\to\Xi^-\pi^+\pi^+$ are measured to be $1.18 \pm 0.26 \pm 0.17$, $0.92 \pm 0.27 \pm 0.14$, and $0.58 \pm 0.16 \pm 0.07$, respectively.Comment: 12 page uuencoded postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Modelling vehicles acceleration during overtaking manoeuvres

[EN] Abstract: Overtaking manoeuvre is a key issue for two-lane rural roads. These roads should provide sufficient overtaking sight distance (OSD) at certain locations to allow faster vehicles to pass slower ones. However, overtaking requires occupying the opposing lane, which represents a serious safety concern. Severity of overtaking related crashes is very high, compared with other manoeuvres. The development of advanced driver assistance systems (ADAS) for overtaking is being a complex task. Only few systems have been developed, but are not still in use. This research incorporated accurate data of real manoeuvres to improve the knowledge of the phenomenon. The trajectory of the overtaking vehicles on the left lane was observed. An instrumented vehicle measured the overtaking time and distance, the abreast position, and the initial and final speed of 180 drivers that passed it during a field experiment. Six different kinematic models (such as uniform acceleration or linear variation of acceleration) were calibrated. Generally, drivers started to accelerate before changing to the opposing lane. These models may be applied to ADAS, to estimate OSD and to improve microsimulation models.Part of this research was included in the project 'Desarrollo de modelos de distancias de visibilidad de adelantamiento', with reference code TRA2010-21736 and subsidised by the Spanish Ministery of Economy and Competitivity. The authors also thank Prof Dr Sayed, from University of British Columbia, for his valuable review.Llorca Garcia, C.; Moreno, AT.; García García, A. (2016). Modelling vehicles acceleration during overtaking manoeuvres. IET Intelligent Transport Systems. 10(3):206-215. https://doi.org/10.1049/iet-its.2015.0035S206215103Gray, R., & Regan, D. M. (2005). Perceptual Processes Used by Drivers During Overtaking in a Driving Simulator. Human Factors: The Journal of the Human Factors and Ergonomics Society, 47(2), 394-417. doi:10.1518/0018720054679443Basilio, N., Morice, A. H. P., Marti, G., & Montagne, G. (2015). High- and Low-Order Overtaking-Ability Affordances. Human Factors: The Journal of the Human Factors and Ergonomics Society, 57(5), 879-894. doi:10.1177/0018720815583581Morice, A. H. P., Diaz, G. J., Fajen, B. R., Basilio, N., & Montagne, G. (2015). An Affordance-Based Approach to Visually Guided Overtaking. Ecological Psychology, 27(1), 1-25. doi:10.1080/10407413.2015.991641Farah, H., Bekhor, S., & Polus, A. (2009). Risk evaluation by modeling of passing behavior on two-lane rural highways. Accident Analysis & Prevention, 41(4), 887-894. doi:10.1016/j.aap.2009.05.006Hassan, Y., Easa, S. M., & El Halim, A. O. A. (1996). Passing sight distance on two-lane highways: Review and revision. Transportation Research Part A: Policy and Practice, 30(6), 453-467. doi:10.1016/0965-8564(95)00032-1Wang, Y., & Cartmell, M. P. (1998). New Model for Passing Sight Distance on Two-Lane Highways. Journal of Transportation Engineering, 124(6), 536-545. doi:10.1061/(asce)0733-947x(1998)124:6(536)Sparks, G. A., Neudorf, R. D., Robinson, J. B. L., & Good, D. (1993). Effect of Vehicle Length on Passing Operations. Journal of Transportation Engineering, 119(2), 272-283. doi:10.1061/(asce)0733-947x(1993)119:2(272)Hanley, P. F., & Forkenbrock, D. J. (2005). Safety of passing longer combination vehicles on two-lane highways. Transportation Research Part A: Policy and Practice, 39(1), 1-15. doi:10.1016/j.tra.2004.09.001Khoury, J. E., & Hobeika, A. G. (2012). Integrated Stochastic Approach for Risk and Service Estimation: Passing Sight Distance Application. Journal of Transportation Engineering, 138(5), 571-579. doi:10.1061/(asce)te.1943-5436.0000366Jenkins, J. M., & Rilett, L. R. (2004). Application of Distributed Traffic Simulation for Passing Behavior Study. Transportation Research Record: Journal of the Transportation Research Board, 1899(1), 11-18. doi:10.3141/1899-02Rakha, H., Ahn, K., & Trani, A. (2004). Development of VT-Micro model for estimating hot stabilized light duty vehicle and truck emissions. Transportation Research Part D: Transport and Environment, 9(1), 49-74. doi:10.1016/s1361-9209(03)00054-3Polus, A., Livneh, M., & Frischer, B. (2000). Evaluation of the Passing Process on Two-Lane Rural Highways. Transportation Research Record: Journal of the Transportation Research Board, 1701(1), 53-60. doi:10.3141/1701-07Harwood, D. W., Gilmore, D. K., & Richard, K. R. (2010). Criteria for Passing Sight Distance for Roadway Design and Marking. Transportation Research Record: Journal of the Transportation Research Board, 2195(1), 36-46. doi:10.3141/2195-05Hegeman, G., Tapani, A., & Hoogendoorn, S. (2009). Overtaking assistant assessment using traffic simulation. Transportation Research Part C: Emerging Technologies, 17(6), 617-630. doi:10.1016/j.trc.2009.04.010Milanés, V., Llorca, D. F., Villagrá, J., Pérez, J., Fernández, C., Parra, I., … Sotelo, M. A. (2012). Intelligent automatic overtaking system using vision for vehicle detection. Expert Systems with Applications, 39(3), 3362-3373. doi:10.1016/j.eswa.2011.09.024Isermann, R., Mannale, R., & Schmitt, K. (2012). Collision-avoidance systems PRORETA: Situation analysis and intervention control. Control Engineering Practice, 20(11), 1236-1246. doi:10.1016/j.conengprac.2012.06.003Petrov, P., & Nashashibi, F. (2014). Modeling and Nonlinear Adaptive Control for Autonomous Vehicle Overtaking. IEEE Transactions on Intelligent Transportation Systems, 15(4), 1643-1656. doi:10.1109/tits.2014.2303995Llorca, C., & García, A. (2011). Evaluation of Passing Process on Two-Lane Rural Highways in Spain with New Methodology Based on Video Data. Transportation Research Record: Journal of the Transportation Research Board, 2262(1), 42-51. doi:10.3141/2262-05Llorca, C., Moreno, A. T., García, A., & Pérez-Zuriaga, A. M. (2013). Daytime and Nighttime Passing Maneuvers on a Two-Lane Rural Road in Spain. Transportation Research Record: Journal of the Transportation Research Board, 2358(1), 3-11. doi:10.3141/2358-01Llorca, C., Moreno, A. T., Pérez-Zuriaga, A. M., & García, A. (2013). Influence of age, gender and delay on overtaking dynamics. IET Intelligent Transport Systems, 7(2), 174-181. doi:10.1049/iet-its.2012.0147Khoury, J. E., & Hobeika, A. (2007). Incorporating Uncertainty into the Estimation of the Passing Sight Distance Requirements. Computer-Aided Civil and Infrastructure Engineering, 22(5), 347-357. doi:10.1111/j.1467-8667.2007.00491.xRakha, H., Snare, M., & Dion, F. (2004). Vehicle Dynamics Model for Estimating Maximum Light-Duty Vehicle Acceleration Levels. Transportation Research Record: Journal of the Transportation Research Board, 1883(1), 40-49. doi:10.3141/1883-05Fitzpatrick, K., Chrysler, S. T., & Brewer, M. (2012). Deceleration Lengths for Exit Terminals. Journal of Transportation Engineering, 138(6), 768-775. doi:10.1061/(asce)te.1943-5436.000038

Measurement of the Mass Splittings between the bbˉχb,J(1P)b\bar{b}\chi_{b,J}(1P) States

We present new measurements of photon energies and branching fractions for the radiative transitions: Upsilon(2S)->gamma+chi_b(J=0,1,2). The masses of the chi_b states are determined from the measured radiative photon energies. The ratio of mass splittings between the chi_b substates, r==(M[J=2]-M[J=1])/(M[J=1]-M[J=0]) with M the chi_b mass, provides information on the nature of the bbbar confining potential. We find r(1P)=0.54+/-0.02+/-0.02. This value is in conflict with the previous world average, but more consistent with the theoretical expectation that r(1P)<r(2P); i.e., that this mass splittings ratio is smaller for the chi_b(1P) triplet than for the chi_b(2P) triplet.Comment: 11 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN