Feedhorn-integrated THz QCL local oscillators for the LOCUS atmospheric sounder

The LOCUS atmospheric sounder is a satellite-borne THz radiometer concept, for studying molecular species in the mesosphere and lower thermosphere. We report waveguide-integrated THz quantum-cascade lasers for use as 3.5 THz local oscillators. A waveguide-integration scheme, using an integrated diagonal feedhorn significantly improves power outcoupling. 1.3 mW THz emission is demonstrated in a space-qualified Stirling cryocooler at 57 K, with ∼15° beam divergence

Electromagnetic modelling of a terahertz-frequency quantum-cascade laser integrated with dual diagonal feedhorns

We present an electromagnetic model of a THz QCL, integrated with a micro-machined waveguide and dual diagonal feedhorns, enabling simultaneous access to both facets of the QCL. A hybrid finite-element/Fourier transform approach enables analysis of both the near and far-fields in agreement with experimental observations. The far-field pattern shows enhancement of the beam profile when compared with an unmounted QCL, in terms of beam divergence and side-lobe suppression ratio

Electromagnetic-field analysis of diagonal-feedhorn antennas for terahertz-frequency quantum-cascade laser integration

We present an electromagnetic-field analysis of a terahertz-frequency quantum-cascade laser (THz QCL) integrated with a mechanically micro-machined waveguide cavity and diagonal feedhorn. A hybrid finite-element/Fourier transform approach enables analysis of both the near-field and far-field regions and is shown to agree well with experimental observations. The far-field antenna patterns show enhancement of the beam profile when compared with an unmounted QCL, in terms of beam divergence and side-lobe suppression ratio. Furthermore, we demonstrate integration of the QCL with dual diagonal feedhorns, enabling simultaneous access to both facets of the QCL, underpinning future integration with a satellite-based receiver and frequency-stabilization subsystem

Quantum‐Cascade Laser emission at 3.5 THz from dual diagonal feedhorns

The LOCUS satellite (Linking Observations of Climate, the Upper Atmosphere and Space weather) is a proposed mission to explore and observe key gas species within the upper atmosphere using a novel terahertz-frequency (THz) heterodyne spectrometer, in which the emission spectra are simultaneously recorded in four channels in the 0.8–4.7 THz band [1]. THz quantum-cascade lasers (QCLs) will be exploited as local oscillators for the first time in space because they are powerful, yet compact THz sources, providing > 1 mW continuous-wave output at key LOCUS frequencies (3.5 and 4.7 THz). Furthermore, they have been integrated successfully into precision-micro-machined waveguide blocks and operated in space-qualified Stirling-cycle cryo-coolers (~60 K) [2]. A key development challenge will be stabilising the emission frequency of the QCL by locking it to a stable reference oscillator. In this paper, we present a new QCL dual-feedhorn integration technique, which advances this goal by enabling access to radiation emitted from both facets of the QCL simultaneously. In this configuration, the THz emission may be coupled simultaneously to a mixer and to a stabilisation subsystem. Figure 1(a) shows the integration of a 3.5 THz QCL into a precision micro-machined channel in a copper block. A second, symmetrical copper block is placed on top of this to form a rectangular waveguide around the QCL, with a diagonal feedhorn at either end. Figure 1(b) shows the simulated far-field beam pattern for a single feedhorn at 3.5 THz, in which the maximum collected power is represented in the bright central area. Figure 1(c) shows the experimental results for the dual-feedhorn waveguide block, in which the radiation from each horn is reflected onto the same plane, and measured using a raster-scanned Golay-cell detector. Good agreement with the simulated single-feedhorn emission has been observed, with similar beam width and side-lobe content. In conclusion, the integration of a 3.5-THz QCL into a dual-feedhorn waveguide block has been demonstrated. This opens the way towards simultaneous integration of the QCL with a frequency stabilisation system and a supra-THz mixer

3.5 THz quantum-cascade laser emission from dual diagonal feedhorns

Antenna-pattern measurements obtained from a double-metal supra-terahertz-frequency (supra-THz) quantum cascade laser (QCL) are presented. The QCL is mounted within a mechanically micro-machined waveguide cavity containing dual diagonal feedhorns. Operating in continuous-wave mode at 3.5 THz, and at an ambient temperature of ∼60 K, QCL emission has been directed via the feedhorns to a supra-THz detector mounted on a multi-axis linear scanner. Comparison of simulated and measured far-field antenna patterns shows an excellent degree of correlation between beamwidth (full-width-half-maximum) and sidelobe content and a very substantial improvement when compared with unmounted devices. Additionally, a single output has been used to successfully illuminate and demonstrate an optical breadboard arrangement associated with a future supra-THz Earth observation space-borne payload. Our novel device has therefore provided a valuable demonstration of the effectiveness of supra-THz diagonal feedhorns and QCL devices for future space-borne ultra-high-frequency Earth-observing heterodyne radiometers

ClinGen Myeloid Malignancy Variant Curation Expert Panel recommendations for germline RUNX1 variants

Standardized variant curation is essential for clinical care recommendations for patients with inherited disorders. Clinical Genome Resource (ClinGen) variant curation expert panels are developing disease-associated gene specifications using the 2015 American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines to reduce curation discrepancies. The ClinGen Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP) was created collaboratively between the American Society of Hematology and ClinGen to perform gene- and disease-specific modifications for inherited myeloid malignancies. The MM-VCEP began optimizing ACMG/AMP rules for RUNX1 because many germline variants have been described in patients with familial platelet disorder with a predisposition to acute myeloid leukemia, characterized by thrombocytopenia, platelet functional/ultrastructural defects, and a predisposition to hematologic malignancies. The 28 ACMG/AMP codes were tailored for RUNX1 variants by modifying gene/disease specifications, incorporating strength adjustments of existing rules, or both. Key specifications included calculation of minor allele frequency thresholds, formulating a semi-quantitative approach to counting multiple independent variant occurrences, identifying functional domains and mutational hotspots, establishing functional assay thresholds, and characterizing phenotype-specific guidelines. Preliminary rules were tested by using a pilot set of 52 variants; among these, 50 were previously classified as benign/likely benign, pathogenic/likely pathogenic, variant of unknown significance (VUS), or conflicting interpretations (CONF) in ClinVar. The application of RUNX1-specific criteria resulted in a reduction in CONF and VUS variants by 33%, emphasizing the benefit of gene-specific criteria and sharing internal laboratory data.Xi Luo, Simone Feurstein, Shruthi Mohan, Christopher C. Porter, Sarah A. Jackson, Sioban Keel ... et al

An Integrated 3.5-THz QCL Optical Breadboard System for the LOCUS Atmospheric Sounder

An “elegant breadboard” system has been developed, which demonstrates the integration of terahertz-frequency (THz) sources, optics and compact cryocooler technology for the LOCUS satellite (Linking Observations of Climate, the Upper Atmosphere and Space Weather). This proposed satellite instrument has the aim of providing the first global mapping of key molecular species within the mesosphere and lower thermosphere (MLT) from low-earth orbit (LEO), using compact radiometers operating in the 0.8–4.7 THz band and a set of infrared detectors. The LOCUS THz radiometers will incorporate planar-Schottky-diode (SD) mixers, driven using waveguide-integrated local-oscillators (LOs). The LOs will be based on SD multipliers operating at 0.8 and 1.1 THz, and THz quantum-cascade lasers (QCLs) operating at 3.5 and 4.7 THz. A key technological challenge, addressed by the LOCUS elegant breadboard, is the integration of these components into a compact and robust satellite payload, including space-qualified cryocooler technology, and suitable fore-optics. In this paper, we discuss recent progress in QCL integration within the 3.5-THz channel

Rational Redesign of Glucose Oxidase for Improved Catalytic Function and Stability

Glucose oxidase (GOx) is an enzymatic workhorse used in the food and wine industries to combat microbial contamination, to produce wines with lowered alcohol content, as the recognition element in amperometric glucose sensors, and as an anodic catalyst in biofuel cells. It is naturally produced by several species of fungi, and genetic variants are known to differ considerably in both stability and activity. Two of the more widely studied glucose oxidases come from the species Aspergillus niger (A. niger) and Penicillium amagasakiense (P. amag.), which have both had their respective genes isolated and sequenced. GOx from A. niger is known to be more stable than GOx from P. amag., while GOx from P. amag. has a six-fold superior substrate affinity (KM) and nearly four-fold greater catalytic rate (kcat). Here we sought to combine genetic elements from these two varieties to produce an enzyme displaying both superior catalytic capacity and stability. A comparison of the genes from the two organisms revealed 17 residues that differ between their active sites and cofactor binding regions. Fifteen of these residues in a parental A. niger GOx were altered to either mirror the corresponding residues in P. amag. GOx, or mutated into all possible amino acids via saturation mutagenesis. Ultimately, four mutants were identified with significantly improved catalytic activity. A single point mutation from threonine to serine at amino acid 132 (mutant T132S, numbering includes leader peptide) led to a three-fold improvement in kcat at the expense of a 3% loss of substrate affinity (increase in apparent KM for glucose) resulting in a specify constant (kcat/KM) of 23.8 (mM−1 · s−1) compared to 8.39 for the parental (A. niger) GOx and 170 for the P. amag. GOx. Three other mutant enzymes were also identified that had improvements in overall catalysis: V42Y, and the double mutants T132S/T56V and T132S/V42Y, with specificity constants of 31.5, 32.2, and 31.8 mM−1 · s−1, respectively. The thermal stability of these mutants was also measured and showed moderate improvement over the parental strain

Optical Breadboard Integration of a 3.5-THz Quantum-Cascade Laser Local-Oscillator for the LOCUS Atmospheric Sounder

An “elegant breadboard” system has been developed, which demonstrates the integration of terahertz-frequency (THz) sources, optics and compact cryocooler technology for the LOCUS satellite (Linking Observations of Climate, the Upper Atmosphere and Space Weather). This proposed satellite instrument has the aim of providing the first global mapping of key molecular species within the mesosphere and lower thermosphere (MLT) from low-earth orbit (LEO), using compact radiometers operating in the 0.8–4.7 THz band and a set of infrared detectors. The LOCUS THz radiometers will incorporate planar-Schottky-diode (SD) mixers, driven using waveguide-integrated local-oscillators (LOs). The LOs will be based on SD multipliers operating at 0.8 and 1.1 THz, and THz quantum-cascade lasers (QCLs) operating at 3.5 and 4.7 THz. A key technological challenge, addressed by the LOCUS elegant breadboard, is the integration of these components into a compact and robust satellite payload, including space-qualified cryocooler technology, and suitable fore-optics. In this paper, we discuss recent progress in QCL integration within the 3.5-THz channel

Structural Basis for Specificity of Propeptide-Enzyme Interaction in Barley C1A Cysteine Peptidases

C1A cysteine peptidases are synthesized as inactive proenzymes. Activation takes place by proteolysis cleaving off the inhibitory propeptide. The inhibitory capacity of propeptides from barley cathepsin L and B-like peptidases towards commercial and barley cathepsins has been characterized. Differences in selectivity have been found for propeptides from L-cathepsins against their cognate and non cognate enzymes. Besides, the propeptide from barley cathepsin B was not able to inhibit bovine cathepsin B. Modelling of their three-dimensional structures suggests that most propeptide inhibitory properties can be explained from the interaction between the propeptide and the mature cathepsin structures. Their potential use as biotechnological tools is discussed