pH-dependent effects of procaine on equine gamete activation

Procaine directly triggers pH-dependent cytokinesis in equine oocytes and induces hypermotility in stallion spermatozoa, an important event during capacitation. However, procaine-induced hyperactivated motility is abolished when sperm is washed to remove the procaine prior to sperm-oocyte co-incubation. To understand how procaine exerts its effects, the external Ca2+ and Na+ and weak base activity dependency of procaine-induced hyperactivation in stallion spermatozoa was assessed using computer-assisted sperm analysis. Percoll-washed stallion spermatozoa exposed to Ca2+-depleted (+2 mM EGTA) procaine-supplemented capacitating medium (CM) still demonstrated hyperactivated motility, whereas CM without NaCl or Na+ did not. Both procaine and NH4Cl, another weak base, were shown to trigger a cytoplasmic pH increase (BCECF-acetoxymethyl (AM)), which is primarily induced by a pH rise in acidic cell organelles (Lysosensor green dnd-189), accompanied by hypermotility in stallion sperm. As for procaine, 25 mM NH4Cl also induced oocyte cytokinesis. Interestingly, hyperactivated motility was reliably induced by 2.5-10 mM procaine, whereas a significant cytoplasmic cAMP increase and tail-associated protein tyrosine phosphorylation were only observed at 10 mM. Moreover, 25 mM NH4Cl did not support the latter capacitation characteristics. Additionally, cAMP levels were more than 10x higher in boar than stallion sperm incubated under similar capacitating conditions. Finally, stallion sperm preincubated with 10 mM procaine did not fertilize equine oocytes. In conclusion, 10 mM procaine causes a cytoplasmic and acidic sperm cell organelle pH rise that simultaneously induces hyperactivated motility, increased levels of cAMP and tail-associated protein tyrosine phosphorylation in stallion spermatozoa. However, procaine-induced hypermotility is independent of the cAMP/protein tyrosine phosphorylation pathway

Relativistic spherical plasma waves

Tightly focused laser pulses as they diverge or converge in underdense plasma can generate wake waves, having local structures that are spherical waves. Here we report on theoretical study of relativistic spherical wake waves and their properties, including wave breaking. These waves may be suitable as particle injectors or as flying mirrors that both reflect and focus radiation, enabling unique X-ray sources and nonlinear QED phenomena.Comment: 6 pages; 4 figure

Dimuon production by laser-wakefield accelerated electrons

We analyze $\mu^+\mu^-$ pair production generated by high-energy electrons emerging from a laser-wakefield accelerator. The $\mu^+\mu^-$ pairs are created in a solid thick high-$Z$ target, following the electron accelerating plasma region. Numerical estimates are presented for electron beams obtained presently in the LBL TW laser experiment \cite{C2} and possible future developments. Reactions induced by the secondary bremsstrahlung photons dominate the dimuon production. According to our estimates, a 20 pC electron bunch with energy of 1 (10) GeV may create about 200 (6000) muon pairs. The produced $\mu^\pm$ can be used in studying various aspects of muon-related physics in table top installations. This may be considered as an important step towards the investigation of more complicated elementary processes induced by laser driven electrons.Comment: 14 pages, 5 figure

Laser-heater assisted plasma channel formation in capillary discharge waveguides

A method of creating plasma channels with controllable depth and transverse profile for the guiding of short, high power laser pulses for efficient electron acceleration is proposed. The plasma channel produced by the hydrogen-filled capillary discharge waveguide is modified by a ns-scale laser pulse, which heats the electrons near the capillary axis. This interaction creates a deeper plasma channel within the capillary discharge that evolves on a ns-time scale, allowing laser beams with smaller spot sizes than would otherwise be possible in the unmodified capillary discharge.Comment: 5 pages, 3 figure

Veranderingen in de TNM-classificatie van het hoofd-halscarcinoom

The TNM-classification of the UICC is used for staging malignant tumours worldwide. From 2003 the new revised sixth edition must be used. In comparison with the fifth edition there are some general and some head and neck carcinoma specific alterations. Some designations are introduced if sentinel lymph node procedure or immunohistochemistry or molecular methods have been used. In the revised version some definitions for advanced tumour stages at several head and neck sites are changed. In the new classification of the primary tumour the terms erosion and invasion of cartilage or bone are used. At most head and neck sites T4 is divided in T4a and T4b

On production and asymmetric focusing of flat electron beams using rectangular capillary discharge plasmas

A method for the asymmetric focusing of electron bunches, based on the active plasma lensing technique is proposed. This method takes advantage of the strong inhomogeneous magnetic field generated inside the capillary discharge plasma to focus the ultrarelativistic electrons. The plasma and magnetic field parameters inside the capillary discharge are described theoretically and modeled with dissipative magnetohydrodynamic computer simulations enabling analysis of the capillaries of rectangle cross-sections. Large aspect ratio rectangular capillaries might be used to transport electron beams with high emittance asymmetries, as well as assist in forming spatially flat electron bunches for final focusing before the interaction point.Comment: 16 pages, 7 figures, 1 tabl

Laser beam coupling with capillary discharge plasma for laser wakefield acceleration applications

One of the most robust methods, demonstrated up to date, of accelerating electron beams by laser-plasma sources is the utilization of plasma channels generated by the capillary discharges. These channels, i.e., plasma columns with a minimum density along the laser pulse propagation axis, may optically guide short laser pulses, thereby increasing the acceleration length, leading to a more efficient electron acceleration. Although the spatial structure of the installation is simple in principle, there may be some important effects caused by the open ends of the capillary, by the supplying channels etc., which require a detailed 3D modeling of the processes taking place in order to get a detailed understanding and improve the operation. However, the discharge plasma, being one of the most crucial components of the laser-plasma accelerator, is not simulated with the accuracy and resolution required to advance this promising technology. In the present work, such simulations are performed using the code MARPLE. First, the process of the capillary filling with a cold hydrogen before the discharge is fired, through the side supply channels is simulated. The main goal of this simulation is to get a spatial distribution of the filling gas in the region near the open ends of the capillary. A realistic geometry is used for this and the next stage simulations, including the insulators, the supplying channels as well as the electrodes. Second, the simulation of the capillary discharge is performed with the goal to obtain a time-dependent spatial distribution of the electron density near the open ends of the capillary as well as inside the capillary. Finally, to evaluate effectiveness of the beam coupling with the channeling plasma wave guide and electron acceleration, modeling of laser-plasma interaction was performed with the code INF&RNOComment: 11 pages, 9 figure

Growth and phase velocity of self-modulated beam-driven plasma waves

A long, relativistic charged particle beam propagating in a plasma is subject to the self-modulation instability. This instability is analyzed and the growth rate is calculated, including the phase relation. The phase velocity of the accelerating field is shown to be significantly less than the drive beam velocity. These results indicate that the energy gain of a plasma accelerator driven by a self-modulated beam will be severely limited by dephasing. In the long-beam, strongly-coupled regime, dephasing is reached in less than four e-foldings, independent of beam-plasma parameters

Allosteric modulation of the GTPase activity of a bacterial LRRK2 homolog by conformation-specific Nanobodies

Mutations in the Parkinson's disease (PD)-associated protein leucine-rich repeat kinase 2 (LRRK2) commonly lead to a reduction of GTPase activity and increase in kinase activity. Therefore, strategies for drug development have mainly been focusing on the design of LRRK2 kinase inhibitors. We recently showed that the central RocCOR domains (Roc: Ras of complex proteins; COR: C-terminal of Roc) of a bacterial LRRK2 homolog cycle between a dimeric and monomeric form concomitant with GTP binding and hydrolysis. PD-associated mutations can slow down GTP hydrolysis by stabilizing the protein in its dimeric form. Here, we report the identification of two Nanobodies (NbRoco1 and NbRoco2) that bind the bacterial Roco protein (CtRoco) in a conformation-specific way, with a preference for the GTP-bound state. NbRoco1 considerably increases the GTP turnover rate of CtRoco and reverts the decrease in GTPase activity caused by a PD-analogous mutation. We show that NbRoco1 exerts its effect by allosterically interfering with the CtRoco dimer–monomer cycle through the destabilization of the dimeric form. Hence, we provide the first proof of principle that allosteric modulation of the RocCOR dimer–monomer cycle can alter its GTPase activity, which might present a potential novel strategy to overcome the effect of LRRK2 PD mutations

On the design of experiments to study extreme field limits

We propose experiments on the collision of high intensity electromagnetic pulses with electron bunches and on the collision of multiple electromagnetic pulses for studying extreme field limits in the nonlinear interaction of electromagnetic waves. The effects of nonlinear QED will be revealed in these laser plasma experiments.Comment: 7 pages, 3 figures, 1 table; 15th Advanced Accelerator Concepts Workshop (AAC 2012), Austin, Texas, 10-15 June, 201