The Impact of Dispersion on Amplitude and Frequency Noise in a Yb-fiber Laser Comb

We describe a Yb-fiber based laser comb, with a focus on the relationship between net-cavity dispersion and the frequency noise on the comb. While tuning the net cavity dispersion from anomalous to normal, we measure the amplitude noise (RIN), offset frequency (f_CEO) linewidth, and the resulting frequency noise spectrum on f_CEO. We find that the laser operating at zero net-cavity dispersion has many advantages, including an approximately 100x reduction in free-running f_CEO linewidth and frequency noise power spectral density between laser operation at normal and zero dispersion. In this latter regime, we demonstrate a phase-locked f_CEO beat with low residual noise

Full phase stabilization of a Yb:fiber femtosecond frequency comb via high-bandwidth transducers

We present full phase stabilization of an amplified Yb:fiber femtosecond frequency comb using an intra-cavity electro-optic modulator and an acousto-optic modulator. These transducers provide high servo bandwidths of 580 kHz and 250 kHz for frep and fceo, producing a robust and low phase noise fiber frequency comb. The comb was self-referenced with an f - 2f interferometer and phase locked to an ultra-stable optical reference used for the JILA Sr optical clock at 698 nm, exhibiting 0.21 rad and 0.47 rad of integrated phase errors (over 1 mHz - 1 MHz) respectively. Alternatively, the comb was locked to two optical references at 698 nm and 1064 nm, obtaining 0.43 rad and 0.14 rad of integrated phase errors respectively

VUV frequency combs from below-threshold harmonics

Recent demonstrations of high-harmonic generation (HHG) at very high repetition frequencies (~100 MHz) may allow for the revolutionary transfer of frequency combs to the vacuum ultraviolet (VUV). This advance necessitates unifying optical frequency comb technology with strong-field atomic physics. While strong-field studies of HHG have often focused on above-threshold harmonic generation (photon energy above the ionization potential), for VUV frequency combs an understanding of below-threshold harmonic orders and their generation process is crucial. Here we present a new and quantitative study of the harmonics 7-13 generated below and near the ionization threshold in xenon gas. We show multiple generation pathways for these harmonics that are manifested as on-axis interference in the harmonic yield. This discovery provides a new understanding of the strong-field, below-threshold dynamics under the influence of an atomic potential and allows us to quantitatively assess the achievable coherence of a VUV frequency comb generated through below threshold harmonics. We find that under reasonable experimental conditions temporal coherence is maintained. As evidence we present the first explicit VUV frequency comb structure beyond the 3rd harmonic.Comment: 16 pages, 4 figures, 1 tabl

Infektiologische Erstbeurteilung und erste Abklärungsschritte bei Fieber

Zusammenfassung: Die Erstbeurteilung sowie die ersten Abklärungsschritte bei Patienten mit infektiösen Erkrankungen sind wegen der breiten Differenzialdiagnose anspruchsvoll. Der klinische Ersteindruck, die Anamneseerhebung, die gewissenhafte körperliche Untersuchung und das Routinelabor ermöglichen eine vorläufige Diagnose und Therapie. Leitbeschwerden engen die Differenzialdiagnose wesentlich ein. Bei lebensbedrohlichen Erkrankungen wie Sepsis, Endokarditis, bakterieller Meningitis oder schwerer Pneumonie müssen die ersten diagnostischen und therapeutischen Schritte rasch erfolgen: Nach Abnahme bakteriologischer Proben aus Blut, Liquor und/oder Sputum ist eine empirische Antibiotikatherapie rasch zu initiieren; das der Erkrankung mutmaßlich zugrunde liegende bakterielle Erregerspektrum muss dadurch abgedeckt sein. In weniger dringlichen Fällen lohnt sich ein Abklärungsverfahren in mehreren Schritten. In dieser Situation ist es wichtig, die mikrobiologische Diagnose abzuwarten, um eine erreger- und resistenzgerechte Antibiotikatherapie durchführen zu können. Atypische Verläufe müssen eine erneute Diagnostik auslösen, wobei die Diagnose kritisch zu beurteilen und neue Differenzialdiagnosen in Betracht zu ziehen sin

Synthesis, radiolabelling and in vitro and in vivo evaluation of a novel fluorinated ABP688 derivative for the PET imaging of metabotropic glutamate receptor subtype 5

(E)-3-(Pyridin-2-ylethynyl)cyclohex-2-enone O-(2-(3-18F-fluoropropoxy)ethyl) oxime ([18F]-PSS223) was evaluated in vitro and in vivo to establish its potential as a PET tracer for imaging metabotropic glutamate receptor subtype 5 (mGluR5). [18F]-PSS223 was obtained in 20% decay corrected radiochemical yield whereas the non-radioactive PSS223 was accomplished in 70% chemical yield in a SN2 reaction of common intermediate mesylate 8 with potassium fluoride. The in vitro binding affinity of [18F]-PSS223 was measured directly in a Scatchard assay to give Kd = 3.34 ± 2.05 nM. [18F]-PSS223 was stable in PBS and rat plasma but was significantly metabolized by rat liver microsomal enzymes, but to a lesser extent by human liver microsomes. Within 60 min, 90% and 20% of [18F]-PSS223 was metabolized by rat and human microsome enzymes, respectively. In vitro autoradiography on horizontal rat brain slices showed heterogeneous distribution of [18F]-PSS223 with the highest accumulation in brain regions where mGluR5 is highly expressed (hippocampus, striatum and cortex). Autoradiography in vitro under blockade conditions with ABP688 confirmed the high specificity of [18F]-PSS223 for mGluR5. Under the same blocking conditions but using the mGluR1 antagonist, JNJ16259685, no blockade was observed demonstrating the selectivity of [18F]-PSS223 for mGluR5 over mGluR1. Despite favourable in vitro properties of [18F]-PSS223, a clear-cut visualization of mGluR5- rich brain regions in vivo in rats was not possible mainly due to a fast clearance from the brain and low metabolic stability of [18F]-PSS223

Frequency Comb Assisted Diode Laser Spectroscopy for Measurement of Microcavity Dispersion

While being invented for precision measurement of single atomic transitions, frequency combs have also become a versatile tool for broadband spectroscopy in the last years. In this paper we present a novel and simple approach for broadband spectroscopy, combining the accuracy of an optical fiber-laser-based frequency comb with the ease-of-use of a tunable external cavity diode laser. This scheme enables broadband and fast spectroscopy of microresonator modes and allows for precise measurements of their dispersion, which is an important precondition for broadband optical frequency comb generation that has recently been demonstrated in these devices. Moreover, we find excellent agreement of measured microresonator dispersion with predicted values from finite element simulations and we show that tailoring microresonator dispersion can be achieved by adjusting their geometrical properties

Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Aspergillus Lung Infections In Vivo

This is the final published versionAvailable from Ivyspring International Publisher via the DOI in this recordInvasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of hematological malignancy and bone marrow transplant patients caused by the ubiquitous environmental fungus Aspergillus fumigatus. Current diagnostic tests for the disease lack sensitivity as well as specificity, and culture of the fungus from invasive lung biopsy, considered the gold standard for IPA detection, is slow and often not possible in critically ill patients. In a previous study, we reported the development of a novel non-invasive procedure for IPA diagnosis based on antibody-guided positron emission tomography and magnetic resonance imaging (immunoPET/MRI) using a [64Cu]DOTA-labeled mouse monoclonal antibody (mAb), mJF5, specific to Aspergillus. To enable translation of the tracer to the clinical setting, we report here the development of a humanised version of the antibody (hJF5), and pre-clinical imaging of lung infection using a [64Cu]NODAGA-hJF5 tracer. The humanised antibody tracer shows a significant increase in in vivo biodistribution in A. fumigatus infected lungs compared to its radiolabeled murine counterpart [64Cu]NODAGA-mJF5. Using reverse genetics of the pathogen, we show that the antibody binds to the antigenic determinant 1,5-galactofuranose (Galf) present in a diagnostic mannoprotein antigen released by the pathogen during invasive growth in the lung. The absence of the epitope Galf in mammalian carbohydrates, coupled with the enhanced imaging capabilities of the hJF5 antibody, means that the [64Cu]NODAGA-hJF5 tracer developed here represents an ideal candidate for the diagnosis of IPA and translation to the clinical setting.This work was supported by the European Union Seventh Framework Programme FP7/2007-2013 under Grant 602820, the Deutsche Forschungsgemeinschaft (Grant WI3777/1-2 to SW), and the Werner Siemens Foundation. We thank Sven Krappman for use of the A. fumigatustdTomato strain, and acknowledge the Imaging Centre Essen (IMCES) for assistance with optical imaging of lungs