Versatile Control of

We demonstrate quantum control of ^{9}Be^{+} ions directly implemented by an optical frequency comb. Based on numerical simulations of the relevant processes in ^{9}Be^{+} for different magnetic field regimes, we demonstrate a wide applicability when controlling the comb's spectral properties. We introduce a novel technique for the selective and efficient generation of a spectrally tailored narrow-bandwidth optical frequency comb near 313 nm. We experimentally demonstrate internal state control and internal-motional state coupling of ^{9}Be^{+} ions implemented by stimulated-Raman manipulation using a spectrally optimized optical frequency comb. Our pulsed laser approach is a key enabling step for the implementation of quantum logic and quantum information experiments in Penning traps.

Beyond the collaterals: Additional value of multiphase CTA in acute ischemic stroke evaluation.

PURPOSE: Multiphase computed tomography angiography (MP-CTA) is an innovative imaging tool that can give those managing acute ischemic stroke temporal information on degree and extent of pial collateral arterial filling in the affected brain. We sought to estimate the incidence of false-positive or -negative evaluation of the carotid bifurcation or intracranial thrombus on single-phase CTA (SP-CTA) compared with MP-CTA. MATERIAL AND METHODS: A single-center, retrospective consecutive review was conducted of imaging and clinical records of 150 patients in two months who presented with neurological symptoms with a National Institutes of Health Stroke Scale score ≥ 2 and who received an MP-CTA as part of their investigative work-up. The cohort consisted of 52.3% male and 47.7% female patients. Median individual age was 68 years (interquartile range 60-79). Extracranial and intracranial vessel images of the initial early arterial phase were evaluated and compared with late arterial and early venous phase images. RESULTS: In the cohort of 150 patients, in three patients (2%) SP-CTA would have led to an incorrect diagnosis and management without MP-CTA-acquired source imaging. The three scenarios represented differentiating a carotid string sign from internal carotid artery occlusion, determining the appearance and extent of thrombus in carotid T-occlusion, and differentiating slow flow and contrast mixing-related artifacts from intraluminal thrombus. CONCLUSIONS: In addition to improving assessment of collateral circulation in acute stroke patients, MP-CTA is also useful in assessing specific flow-related scenarios for which SP-CTA may give spurious results.

Differential effects on glial activation by a direct versus an indirect thrombin inhibitor.

Thrombin is a potent regulator of brain function in health and disease, modulating glial activation and brain inflammation. Thrombin inhibitors, several of which are in clinical use as anti-coagulants, can reduce thrombin-dependent neuroinflammation in pathological conditions. However, their effects in a healthy CNS are largely unknown. In adult healthy mice, we compared the effects of treatment by the direct thrombin inhibitor dabigatran etexilate (DE), to those of warfarin, which acts by preventing vitamin K recycling essential for coagulation. After 4weeks, warfarin increased both astrocyte GFAP and microglia Iba-1 staining throughout the CNS; whereas DE reduced expression of both markers. Warfarin, but not DE, reduced sulfatide levels; and warfarin showed longer lasting changes in cerebellar gene expression. DE also reduced glial activation in a mouse model of Alzheimer's disease, although no changes in amyloid plaque burden were observed. These results suggest that treatment with direct thrombin inhibitors may be preferable to those agents which reduce vitamin K levels and have the potential to increase glial activation.

Membrane Cholesterol Modulates Superwarfarin Toxicity.

Superwarfarins are modified analogs of warfarin with additional lipophilic aromatic rings, up to 100-fold greater potency, and longer biological half-lives. We hypothesized that increased hydrophobicity allowed interactions with amphiphilic membranes and modulation of biological responses. We find that superwarfarins brodifacoum and difenacoum increase lactate production and cell death in neuroblastoma cells. In contrast, neither causes changes in glioma cells that have higher cholesterol content. After choleterol depletion, lactate production was increased and cell viability was reduced. Drug-membrane interactions were examined by surface X-ray scattering using Langmuir monolayers of dipalmitoylphosphatidylcholine and/or cholesterol. Specular X-ray reflectivity data revealed that superwarfarins, but not warfarin, intercalate between dipalmitoylphosphatidylcholine molecules, whereas grazing incidence X-ray diffraction demonstrated changes in lateral crystalline order of the film. Neither agent showed significant interactions with monolayers containing >20% cholesterol. These findings demonstrate an affinity of superwarfarins to biomembranes and suggest that cellular responses to these agents are regulated by cholesterol content.

Stimulated Raman gas sensing by backward UV lasing from a femtosecond filament.

We perform a proof-of-principle demonstration of chemically specific standoff gas sensing, in which a coherent stimulated Raman signal is detected in the direction anticollinear to a two-color laser excitation beam traversing the target volume. The proposed geometry is intrinsically free space as it does not involve back-scattering (reflection) of the signal or excitation beams at or behind the target. A beam carrying an intense mid-IR femtosecond (fs) pulse and a parametrically generated picosecond (ps) UV Stokes pulse is fired in the forward direction. A fs filament, produced by the intense mid-IR pulse, emits a backward-propagating narrowband ps laser pulse at the 337 and 357 nm transitions of excited molecular nitrogen, thus supplying a counter-propagating Raman pump pulse. The scheme is linearly sensitive to species concentration and provides both transverse and longitudinal spatial resolution.

A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration.

NAD metabolism regulates diverse biological processes, including ageing, circadian rhythm and axon survival. Axons depend on the activity of the central enzyme in NAD biosynthesis, nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2), for their maintenance and degenerate rapidly when this activity is lost. However, whether axon survival is regulated by the supply of NAD or by another action of this enzyme remains unclear. Here we show that the nucleotide precursor of NAD, nicotinamide mononucleotide (NMN), accumulates after nerve injury and promotes axon degeneration. Inhibitors of NMN-synthesising enzyme NAMPT confer robust morphological and functional protection of injured axons and synapses despite lowering NAD. Exogenous NMN abolishes this protection, suggesting that NMN accumulation within axons after NMNAT2 degradation could promote degeneration. Ectopic expression of NMN deamidase, a bacterial NMN-scavenging enzyme, prolongs survival of injured axons, providing genetic evidence to support such a mechanism. NMN rises prior to degeneration and both the NAMPT inhibitor FK866 and the axon protective protein Wld(S) prevent this rise. These data indicate that the mechanism by which NMNAT and the related Wld(S) protein promote axon survival is by limiting NMN accumulation. They indicate a novel physiological function for NMN in mammals and reveal an unexpected link between new strategies for cancer chemotherapy and the treatment of axonopathies.

Valoración no invasiva de la estenosis carotídea de causa aterosclerótica: correlación entre la ecografía Doppler color y la angiografía por resonancia magnética con gadolinio

Introducción: La angiografía carotídea se utiliza para confi rmar la presencia de estenosis de la bifurcación carotídea (BC). Sin embargo, dado que este método resulta invasivo y presenta cierta morbimortalidad, existe un creciente interés en los métodos no invasivos, como la angiografía por resonancia magnética con gadolinio (ARM-Gd) y la ecografía Doppler color (EDC). El objetivo de este trabajo es determinar la correlación que existe entre la ecografía Doppler color y la angiografía por resonancia magnética con gadolinio en la determinación del grado de estenosis. Materiales y métodos: Se analizaron por ecografía Doppler color y angiografía por resonancia magnética con gadolinio 100 estudios de la bifurcación carotídea, realizados entre enero de 2009 y agosto de 2011 en el Sanatorio Allende. Se determinó el coefi ciente de concordancia Kappa, evaluando por ecografía Doppler color el porcentaje de estenosis carotídea según la reducción del diámetro y la velocidad sistólica máxima (VSM) y por angiografía por resonancia magnética con gadolinio la reducción de la luz visualizada. En ambos métodos se empleó el criterio de NASCET. También se analizó la superfi cie de la placa. Resultados: Se obtuvo una muy buena correlación entre la ecografía Doppler color y la angiografía por resonancia magnética con gadolinio, con un coefi ciente de concordancia Kappa de 0,90 y un intervalo de confi anza (IC) de 95% (0,786-0,99). Sin embargo, existió una discordancia para valoar la superfi cie de la placa, que dejó en evidencia la superioridad de la angiografía por resonancia magnética con gadolinio para defi nir la superfi cie irregular y/o ulcerada. Conclusión: El avance de la tecnología y el creciente número de estudios que demuestran la fi abilidad y correlación diagnóstica de los métodos no invasivos hacen suponer que en un corto plazo estos reemplazarán a la angiografía en el diagnóstico y valoración de la patología carotídea.

Introduction: Carotid angiography is used to confi rm carotid bifurcation (CB) stenosis. However, it is an invasive method that involves some morbidity. For this reason there is growing interest in non-invasive methods for the evaluation of carotid stenosis, including magnetic resonance angiography with gadolinium (MRAG) and color Doppler ultrasound (USDC). The aim of this study is to determine the correlation between the color Doppler ultrasound and magnetic resonance angiography with gadolinium in the evaluation of the degree of stenosis. Materials and methods: One hundred carotid bifurcations were studied by color Doppler ultrasound and magnetic resonance angiography with gadolinium between January 2009 and August 2011 in Sanatorio Allende. The level of agreement was determined using the Kappa coeffi cient, analyzing the percentage of carotid stenosis with color Doppler ultrasound according to the maximum systolic speed and the stenosis seen by magnetic resonance angiography with gadolinium, using the NASCET criteria for both methods. Results: An excellent correlation was obtained between Doppler ultrasound and magnetic resonance angiography with gadolinium, with a Kappa coeffi cient of 0.90 (95% CI: 0.786-0.99). There was disagreement between the two methods in assessing the plaque surface, showing that magnetic resonance angiography with gadolinium was better for detecting an irregular surface and / or ulcerated plaque. Conclusion: The technological improvement and the increase in reliable studies that have a good diagnostic correlation with non-invasive methods, it could be assumed that, in a short period of time, Doppler ultrasound will gradually replace angiography in the diagnosis of carotid pathology.

Inhibition of fast axonal transport by pathogenic SOD1 involves activation of p38 MAP kinase.

Dying-back degeneration of motor neuron axons represents an established feature of familial amyotrophic lateral sclerosis (FALS) associated with superoxide dismutase 1 (SOD1) mutations, but axon-autonomous effects of pathogenic SOD1 remained undefined. Characteristics of motor neurons affected in FALS include abnormal kinase activation, aberrant neurofilament phosphorylation, and fast axonal transport (FAT) deficits, but functional relationships among these pathogenic events were unclear. Experiments in isolated squid axoplasm reveal that FALS-related SOD1 mutant polypeptides inhibit FAT through a mechanism involving a p38 mitogen activated protein kinase pathway. Mutant SOD1 activated neuronal p38 in mouse spinal cord, neuroblastoma cells and squid axoplasm. Active p38 MAP kinase phosphorylated kinesin-1, and this phosphorylation event inhibited kinesin-1. Finally, vesicle motility assays revealed previously unrecognized, isoform-specific effects of p38 on FAT. Axon-autonomous activation of the p38 pathway represents a novel gain of toxic function for FALS-linked SOD1 proteins consistent with the dying-back pattern of neurodegeneration characteristic of ALS.

Active management of selective intrauterine growth restriction with abnormal Doppler in monochorionic diamniotic twin pregnancies diagnosed in the second trimester of pregnancy.

OBJECTIVE: This study aims to compare outcomes of active management of monochorionic diamniotic twin pregnancies complicated with severe intrauterine growth restriction (IUGR) of one twin before 24 weeks with continuous or intermittent absent or reversed end-diastolic flow (AREDF) in the umbilical artery, with or without twin-to-twin transfusion syndrome (TTTS). METHOD: This study is a retrospective comparison of 45 consecutive cases of severe selective IUGR (s-IUGR) defined as an estimated fetal weight at or below the fifth centile with a >25% weight discordance and AREDF in the umbilical artery before 24 weeks and 166 consecutive cases of TTTS stage III, with AREDF in the donor (TTTS3D) and also with s-IUGR. These were treated by either selective laser photocoagulation of chorionic vessels (SLPCV) or cord coagulation (CC). RESULTS: The 166 cases of TTTS3D were treated by SLPCV, whereas 23 and 22 cases of s-IUGR were treated by SLPCV and CC, respectively. Overall survival was 52.17% or 45.45% in s-IUGR treated by SLPCV or CC, respectively, and 48.49% in TTTS3D. The survival of appropriately grown for gestational age (AGA) twins following CC (90.9%) was higher than that following SLPCV in s-IUGR (74%) or in recipient twins of TTTS3D (55.42%) (p = 0.001). Survival of the IUGR twin was 30% and 41.56% with SLPCV in s-IUGR and TTTS3D, respectively. CONCLUSIONS: Active management of severe IUGR with AREDF in the umbilical artery seems beneficial. Survival rates with SLPCV were similar in s-IUGR and TTTS3D. However, there was a trend for higher survival rates in the AGA twin for CC. The choice of the technique should be driven by objective counseling on survival of both IUGR and AGA twins and therefore by the utility-based ethical values expressed by the pregnant woman.

Analysis of the feed-forward method for the referencing of a CW laser to a frequency comb.

We report on a comprehensive theoretical and experimental analysis of the feed-forward method for external frequency stabilization of a continuous wave laser against a frequency comb. Application of the method to a distributed feedback diode laser at 1.55 µm allows line narrowing from 800 to 10 kHz, with frequency noise reduction by more than 2 decades up to a Fourier frequency of 100 kHz and a maximum control bandwidth of 0.8 MHz. The results are consistent with a relative phase fluctuation of 1.4 rad rms, as limited by uncompensated high-frequency noise of the slave laser.

Ultrafast-laser-induced backward stimulated Raman scattering for tracing atmospheric gases.

By combining tunable broadband pulse generation with the technique of nonlinear spectral compression we demonstrate a prototype scheme for highly selective detection of air molecules by backward stimulated Raman scattering. The experimental results allow to extrapolate the laser parameters required for standoff sensing based on the recently demonstrated backward atmospheric lasing.

Wide-bandwidth phase lock between a CW laser and a frequency comb based on a feed-forward configuration.

Wide-bandwidth phase lock between the tooth of a frequency comb and a CW extended-cavity diode laser at 1.55 µm is achieved by the use of an acousto-optical frequency shifter in a feed-forward configuration. The coherence properties of the comb are efficiently transferred to the CW laser, whose linewidth is narrowed down to the ∼10 KHz comb level. A maximum control bandwidth of ∼0.6 MHz has been experimentally achieved, limited by the transit time of the acoustic wave inside the frequency shifter.

Absolute frequency spectroscopy of CO2 lines at around 2.09 µm by combined use of an Er:fiber comb and a Ho:YLF amplifier.

The low-frequency tail of an octave-spanning supercontinuum (SC) generated by an Er:fiber comb is enhanced by a multipass Ho:YLF amplifier and used in a sum-frequency-generation scheme to obtain absolute referencing of a single-mode Tm-Ho:YAG laser tunable around 2.09 µm. By tuning the comb repetition frequency, the probing laser is scanned across the absorption lines of a CO(2) gas sample and highly accurate absorption profiles are measured. This approach can be readily scaled to any wavelength above ~2 µm.

Background-free broadband CARS spectroscopy from a 1-MHz ytterbium laser.

We introduce a novel configuration for broadband, time-resolved CARS spectroscopy/microscopy in which pump, Stokes and probe pulses are all derived from a single femtosecond Yb:KYW laser. The 1-MHz repetition rate of the system allows very intense CARS signals to be obtained over short acquisition times, while a delayed probe pulse ensures an efficient non-resonant background suppression.

High-precision molecular interrogation by direct referencing of a quantum-cascade-laser to a near-infrared frequency comb.

This work presents a very simple yet effective way to obtain direct referencing of a quantum-cascade-laser at 4.3 µm to a near-IR frequency-comb. Precise tuning of the comb repetition-rate allows the quantum-cascade-laser to be scanned across absorption lines of a CO2 gaseous sample and line profiles to be acquired with extreme reproducibility and accuracy. By averaging over 50 acquisitions, line-centre frequencies are retrieved with an uncertainty of 30 kHz in a linear interaction regime. The extension of this methodology to other lines and molecules, by the use of widely tunable extended-cavity quantum-cascade-lasers, paves the way to a wide availability of high-quality and traceable spectroscopic data in the most crucial region for molecular detection and interrogation.

Femtosecond stimulated Raman spectrometer in the 320-520nm range.

Multi-µJ narrow-bandwidth (≈ 10 cm(-1)) picosecond pulses, broadly tunable in the visible-UV range (320-520 nm), are generated by spectral compression of femtosecond pulses emitted by an amplified Ti:sapphire system. Such pulses provide the ideal Raman pump for broadband femtosecond stimulated Raman spectroscopy, as here demonstrated on a heme protein.