Dynamic and redundant regulation of LRRK2 and LRRK1 expression

Background  

Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene account for a significant proportion of autosomal-dominant and some late-onset sporadic Parkinson's disease. Elucidation of LRRK2 protein function in health and disease provides an opportunity for deciphering molecular pathways important in neurodegeneration. In mammals, LRRK1 and LRRK2 protein comprise a unique family encoding a GTPase domain that controls intrinsic kinase activity. The expression profiles of the murine LRRK proteins have not been fully described and insufficiently characterized antibodies have produced conflicting results in the literature.     

Spectral Networks and Fenchel–Nielsen Coordinates

It is known that spectral networks naturally induce certain coordinate systems on moduli spaces of flat SL(K)-connections on surfaces, previously studied by Fock and Goncharov. We give a self-contained account of this story in the case K = 2 and explain how it can be extended to incorporate the complexified Fenchel–Nielsen coordinates. As we review, the key ingredient in the story is a procedure for passing between moduli of flat SL(2)-connections on C (equipped with a little extra structure) and moduli of equivariant GL(1)-connections over a covering \({\Sigma \to C}\); taking holonomies of the equivariant GL(1)-connections then gives the desired coordinate systems on moduli of SL(2)-connections. There are two special types of spectral network, related to ideal triangulations and pants decompositions of C; these two types of network lead to Fock–Goncharov and complexified Fenchel–Nielsen coordinate systems, respectively.     

Oscillations and concentrations in weak solutions of the incompressible fluid equations

The authors introduce a new concept of measure-valued solution for the 3-D incompressible Euler equations in order to incorporate the complex phenomena present in limits of approximate solutions of these equations. One application of the concepts developed here is the following important result: a sequence of Leray-Hopf weak solutions of the Navier-Stokes equations converges in the high Reynolds number limit to a measure-valued solution of 3-D Euler defined for all positive times. The authors present several explicit examples of solution sequences for 3-D incompressible Euler with uniformly bounded local kinetic energy which exhibit complex phenomena involving both persistence of oscillations and development of concentrations. An extensions of the concept of Young measure is developed to incorporate these complex phenomena in the measure-valued solutions constructed here.Partially supported by N.S.F. GrantPartially supported by N.S.F. Grant 84-0223 and 86-11110     

Ultralow phase noise microwave generation with an Er:fiber-based optical frequency divider

We present an optical frequency divider based on a 200 MHz repetition rate Er:fiber mode-locked laser that, when locked to a stable optical frequency reference, generates microwave signals with absolute phase noise that is equal to or better than cryogenic microwave oscillators. At 1 Hz offset from a 10 GHz carrier, the phase noise is below -100 dBc/Hz, limited by the optical reference. For offset frequencies >10 kHz, the phase noise is shot noise limited at -145 dBc/Hz. An analysis of the contribution of the residual noise from the Er:fiber optical frequency divider is also presented.     

Hardy's paradox and violation of a state-independent Bell inequality in time

Tests such as Bell's inequality and Hardy's paradox show that joint probabilities and correlations between distant particles in quantum mechanics are inconsistent with local realistic theories. Here we experimentally demonstrate these concepts in the time domain, using a photonic entangling gate to perform nondestructive measurements on a single photon at different times. We show that Hardy's paradox is much stronger in time and demonstrate the violation of a temporal Bell inequality independent of the quantum state, including for fully mixed states.     

Beat-to-beat respiratory motion correction with near 100% efficiency: a quantitative assessment using high-resolution coronary artery imaging

This study quantitatively assesses the effectiveness of retrospective beat-to-beat respiratory motion correction (B2B-RMC) at near 100% efficiency using high-resolution coronary artery imaging. Three-dimensional (3D) spiral images were obtained in a coronary respiratory motion phantom with B2B-RMC and navigator gating. In vivo, targeted 3D coronary imaging was performed in 10 healthy subjects using B2B-RMC spiral and navigator gated balanced steady-state free-precession (nav-bSSFP) techniques. Vessel diameter and sharpness in proximal and mid arteries were used as a measure of respiratory motion compensation effectiveness and compared between techniques. Phantom acquisitions with B2B-RMC were sharper than those acquired with navigator gating (B2B-RMC vs. navigator gating: 1.01±0.02 mm⁻¹ vs. 0.86±0.08 mm⁻¹, P<.05). In vivo B2B-RMC respiratory efficiency was significantly and substantially higher (99.7%±0.5%) than nav-bSSFP (44.0%±8.9%, P<.0001). Proximal and mid vessel sharpnesses were similar (B2B-RMC vs. nav-bSSFP, proximal: 1.00±0.14 mm⁻¹ vs. 1.08±0.11 mm⁻¹, mid: 1.01±0.11 mm⁻¹ vs. 1.05±0.12 mm⁻¹; both P=not significant [ns]). Mid vessel diameters were not significantly different (2.85±0.39 mm vs. 2.80±0.35 mm, P=ns), but proximal B2B-RMC diameters were slightly higher (2.85±0.38 mm vs. 2.70±0.34 mm, P<.05), possibly due to contrast differences. The respiratory efficiency of B2B-RMC is less variable and significantly higher than navigator gating. Phantom and in vivo vessel sharpness and diameter values suggest that respiratory motion compensation is equally effective.     

Proton beam writing of Nd:GGG crystals as new waveguide laser sources

Focused proton beam writing has been utilized to fabricate optical channel waveguides in Nd:GGG crystals. The 1?MeV proton beam irradiation creates a local modified region with positive refractive index changes at the end of the proton trajectory, in which the channel waveguide could confine the light field in a symmetric way. Room-temperature laser emission has been achieved at 1063.7?nm, with absorbed pump power of 61?mW (at 808?nm). The obtained slope efficiency of the Nd:GGG waveguide laser system is as high as 66%, which is, to our best knowledge, the highest value for integrated lasers from ion beam processed channel waveguide systems.     

Measurement of the spatial backscattering impulse-response at short length scales with polarized enhanced backscattering

In this Letter, we describe an easy to implement technique to measure the spatial backscattering impulse-response at length scales shorter than a transport mean free path with resolution of better than 10 μm using the enhanced backscattering phenomenon. This technique enables spectroscopic measurements throughout the visible range and sensitivity to all polarization channels. Through a combination of Monte Carlo simulations and experimental measurements of latex microspheres, we explore the various sensitivities of our technique to both intrinsic sample properties and extrinsic instrumental properties. We conclude by demonstrating the extraordinary sensitivity of our technique to the shape of the scattering phase function, including higher order shape parameters than the anisotropy factor (or first moment).     

Chirped pulse amplification in single mode Tm:fiber using a chirped Bragg grating

We report femtosecond pulse generation and chirped pulse amplification in Tm:fiber. A mode-locked oscillator operating in the soliton regime produced 800 fs pulses with 5 nm spectral bandwidth, at 40 pJ pulse energy. This oscillator seeded a pre-amplifier that utilizes a Raman soliton self-frequency shift to produce wavelength tunable pulses with 3 nJ energy, reduced pulse duration of 150 fs, and increased bandwidth of 30 nm. For further amplification, the pulses were stretched up to 160 ps using a chirped Bragg grating (CBG). Stretched pulses were amplified to 85 nJ after compression in single-mode Tm:fiber and recompressed with the CBG as short as 400 fs. Compressed pulses were coupled into a highly nonlinear tellurite fiber to investigate the potential of this ultrashort pulse 2-μm fiber source as a pump for mid-IR supercontinuum generation.     

pH‐sensing nanostar probe using surface‐enhanced Raman scattering (SERS): theoretical and experimental studies

Local pH environment has been considered to be a potential biomarker for tumor diagnosis because solid tumors contain highly acidic environments. A pH‐sensing nanoprobe based on surface‐enhanced Raman scattering (SERS) using nanostars under near‐infrared excitation has been developed for potential biomedical applications. To theoretically investigate the effect of protonation state on SERS spectra of p‐mercaptobenzoic acid (pMBA), we used the density functional theory (DFT) with the B3LYP functional to calculate Raman vibrational spectra of pMBA‐Au/Ag complex in both protonated and deprotonated states. Vibrational spectral bands were assigned with DFT calculation and used to investigate SERS spectral changes observed from experiment when varying pH value between five and nine. The SERS peak position of pMBA at ~1580 cm⁻¹ was identified to be a novel pH‐sensing index, which has small but noticeable downshift with pH increase. This phenomenon is confirmed and well‐explained with theoretical simulation. The study demonstrates that SERS is a sensitive tool to monitor minor structural changes due to local pH environment, and DFT calculations can be used to investigate Raman spectra changes associated with minor differences in molecular structure. Copyright © 2013 John Wiley & Sons, Ltd.