Ultra-Short Optical Pulse Generation with Single-Layer Graphene

Pulses as short as 260 fs have been generated in a diode-pumped low-gain Er:Yb:glass laser by exploiting the nonlinear optical response of single-layer graphene. The application of this novel material to solid-state bulk lasers opens up a way to compact and robust lasers with ultrahigh repetition rates.Comment: 6 pages, 3 figures, to appear in Journal of Nonlinear Optical Physics & Material

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

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

Mode-locked picosecond pulse generation from an octave-spanning supercontinuum

We generate mode-locked picosecond pulses near 1110 nm by spectrally slicing and reamplifying an octave-spanning supercontinuum source pumped at 1550 nm. The 1110 nm pulses are near transform-limited, with 1.7 ps duration over their 1.2 nm bandwidth, and exhibit high interpulse coherence. Both the supercontinuum source and the pulse synthesis system are implemented completely in fiber. The versatile source construction suggests that pulse synthesis from sliced supercontinuum may be a useful technique across the 1000 - 2000 nm wavelength range

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

220 fs Er-Yb:glass laser mode-locked by a broadband low-loss Si/Ge saturable absorber

We demonstrate femtosecond performance of an ultra-broadband high-index-contrast saturable Bragg reflector consisting of a silicon/silicon-dioxide/germanium structure that is fully compatible with CMOS processing. This device offers a reflectivity bandwidth of over 700 nm and sub-picosecond recovery time of the saturable loss. It is used to achieve mode-locking of an Er-Yb:glass laser centered at 1540 nm, generating 220 fs pulses, with the broadest output spectrum to date

Crystal Structure of HIV-1 gp41 Including Both Fusion Peptide and Membrane Proximal External Regions

The HIV-1 envelope glycoprotein (Env) composed of the receptor binding domain gp120 and the fusion protein subunit gp41 catalyzes virus entry and is a major target for therapeutic intervention and for neutralizing antibodies. Env interactions with cellular receptors trigger refolding of gp41, which induces close apposition of viral and cellular membranes leading to membrane fusion. The energy released during refolding is used to overcome the kinetic barrier and drives the fusion reaction. Here, we report the crystal structure at 2 Å resolution of the complete extracellular domain of gp41 lacking the fusion peptide and the cystein-linked loop. Both the fusion peptide proximal region (FPPR) and the membrane proximal external region (MPER) form helical extensions from the gp41 six-helical bundle core structure. The lack of regular coiled-coil interactions within FPPR and MPER splay this end of the structure apart while positioning the fusion peptide towards the outside of the six-helical bundle and exposing conserved hydrophobic MPER residues. Unexpectedly, the section of the MPER, which is juxtaposed to the transmembrane region (TMR), bends in a 90°-angle sideward positioning three aromatic side chains per monomer for membrane insertion. We calculate that this structural motif might facilitate the generation of membrane curvature on the viral membrane. The presence of FPPR and MPER increases the melting temperature of gp41 significantly in comparison to the core structure of gp41. Thus, our data indicate that the ordered assembly of FPPR and MPER beyond the core contributes energy to the membrane fusion reaction. Furthermore, we provide the first structural evidence that part of MPER will be membrane inserted within trimeric gp41. We propose that this framework has important implications for membrane bending on the viral membrane, which is required for fusion and could provide a platform for epitope and lipid bilayer recognition for broadly neutralizing gp41 antibodies

Structure of the St. Louis encephalitis virus postfusion envelope trimer

St. Louis encephalitis virus (SLEV) is a mosquito-borne flavivirus responsible for several human encephalitis outbreaks over the last 80 years. Mature flavivirus virions are coated with dimeric envelope (E) proteins that mediate attachment and fusion with host cells. E is a class II fusion protein, the hallmark of which is a distinct dimer-to-trimer rearrangement that occurs upon endosomal acidification and insertion of hydrophobic fusion peptides into the endosomal membrane. Herein, we report the crystal structure of SLEV E in the posfusion trimer conformation. The structure revealed specific features that differentiate SLEV E from trimers of related flavi- and alphaviruses. SLEV E fusion loops have distinct intermediate spacing such that they are positioned further apart than previously observed in flaviviruses but closer together than Semliki Forest virus, an alphavirus. Domains II and III (DII and DIII) of SLEV E also adopt different angles relative to DI, which suggests that the DI-DII joint may accommodate spheroidal motions. However, trimer interfaces are well conserved among flaviviruses, so it is likely the differences observed represent structural features specific to SLEV function. Analysis of surface potentials revealed a basic platform underneath flavivirus fusion loops that may interact with the anionic lipid head groups found in membranes. Taken together, these results highlight variations in E structure and assembly that may direct virus-specific interactions with host determinants to influence pathogenesis