Cryo-EM structures show the mechanistic basis of pan-peptidase inhibition by human α<inf>2</inf>-macroglobulin

Human α2-macroglobulin (hα2M) is a multidomain protein with a plethora of essential functions, including transport of signaling molecules and endopeptidase inhibition in innate immunity. Here, we dissected the molecular mechanism of the inhibitory function of the ∼720-kDa hα2M tetramer through eight cryo-electron microscopy (cryo-EM) structures of complexes from human plasma. In the native complex, the hα2M subunits are organized in two flexible modules in expanded conformation, which enclose a highly porous cavity in which the proteolytic activity of circulating plasma proteins is tested. Cleavage of bait regions exposed inside the cavity triggers rearrangement to a compact conformation, which closes openings and entraps the prey proteinase. After the expanded-to-compact transition, which occurs independently in the four subunits, the reactive thioester bond triggers covalent linking of the proteinase, and the receptor-binding domain is exposed on the tetramer surface for receptor-mediated clearance from circulation. These results depict the molecular mechanism of a unique suicidal inhibitory trap

Short communication: Determination of lactoferrin in Feta cheese whey with reversed-phase high-performance liquid chromatography

Abstract In the current paper, a method is introduced to determine lactoferrin in sweet whey using reversed-phase HPLC without any pretreatment of the samples or use of a separation technique. As a starting point, the most common HPLC protocols for acid whey, which included pretreatment of the whey along with a sodium dodecyl sulfate-PAGE step, were tested. By skipping the pretreatment and the separation steps while altering the gradient profile, different chromatographs were obtained that proved to be equally efficient to determine lactoferrin. For this novel 1-step reversed-phase HPLC method, repeatability was very high over a wide range of concentrations (1.88% intraday to 5.89% interday). The limit of detection was 35.46μg/mL [signal:noise ratio (S/N)=3], whereas the limit of quantification was 50.86μg/mL (S/N=10). Omitting the pretreatment step caused a degradation of the column's lifetime (to approximately 2,000 samples). As a result, the lactoferrin elution time changed, but neither the accuracy nor the separation ability of the method was significantly influenced. We observed that this degradation could be easily avoided or detained by centrifuging the samples to remove fat or by extensive cleaning of the column after every 5 samples

Multi-material additive manufacture and microwave-assisted sintering of a metal/ceramic metamaterial antenna structure

Multi-material metal/ceramic 3D structures comprising of metallic silver and ultra-low sintering temperature silver molybdenum oxide ceramics, have been additively manufactured and hybrid densified using microwave-assisted sintering for the first time. Optimum densification conditions at 440 °C / 1 h, resulted in relative permittivity, εr = 10.99 ± 0.04, dielectric losses, tanδ = 0.005 ± 0.001 and microwave quality factor, Q × f = 2597 ± 540 GHz. Applying 2 kW microwave energy at 2.45 GHz for 60 min, was proven sufficient, to densify the metallic Ag infilling electrodes, without causing any macroscopic defects. A fully functional multi-layered antenna structure with a metamaterial artificial magnetic conductor was designed, dual-printed and densified, to showcase the potential of combining multi-material additive manufacturing with microwave-assisted sintering

GeantV: Results from the prototype of concurrent vector particle transport simulation in HEP

Full detector simulation was among the largest CPU consumer in all CERN experiment software stacks for the first two runs of the Large Hadron Collider (LHC). In the early 2010's, the projections were that simulation demands would scale linearly with luminosity increase, compensated only partially by an increase of computing resources. The extension of fast simulation approaches to more use cases, covering a larger fraction of the simulation budget, is only part of the solution due to intrinsic precision limitations. The remainder corresponds to speeding-up the simulation software by several factors, which is out of reach using simple optimizations on the current code base. In this context, the GeantV R&D project was launched, aiming to redesign the legacy particle transport codes in order to make them benefit from fine-grained parallelism features such as vectorization, but also from increased code and data locality. This paper presents extensively the results and achievements of this R&D, as well as the conclusions and lessons learnt from the beta prototype.Comment: 34 pages, 26 figures, 24 table

Microwave backscatter enhancement using radial anisotropy in biomimetic core-shell spheres

This is the final version. Available on open access from the American Institute of Physics via the DOI in this record.Data availability: The data that support the findings of this study are available from the corresponding authors upon reasonable request.Enhanced backscattering of microwave radiation is demonstrated experimentally in a biomimetic radially anisotropic spherical metamaterial component. The core-shell device replicates the optical function of nanospheres observed in the tapetum reflector of the compound eye of the shrimp Litopenaeus vannamei (Boone, 1931) and translates the effect from the optical domain to microwave frequencies. Analytical Mie theory calculations and numerical-method simulations are used to describe the origin of the observed scattering from a single dielectric sphere in terms of its multipolar Mie resonances. The fabrication of components using additive manufacture and their experimental characterization are described. The results show that the introduction of radial anisotropy in the shell more than doubles the monostatic radar cross section compared to the equivalent isotropic case. This work represents a practical demonstration of a synthetic bio-inspired structure, harnessing performance-enhancing adaptations that have evolved in nature. The results augment the range of techniques available for the control of electromagnetic scattering with relevance to applications in the manipulation of radar return signals.Engineering and Physical Sciences Research Council (EPSRC)Royal Academy of Engineerin

Multi-material additive manufacturing of low sintering temperature Bi2Mo2O9 ceramics with Ag floating electrodes by selective laser burnout

Additive manufacturing (AM) of co-fired low temperature ceramics offers a unique route for fabrication of novel 3D radio frequency (RF) and microwave communication components, embedded electronics and sensors. This paper describes the first-ever direct 3D printing of low temperature co-fired ceramics/floating electrode 3D structures. Slurry-based AM and selective laser burnout (SLB) were used to fabricate bulk dielectric, Bi2Mo2O9 (BMO, sintering temperature = 620–650°C, εr = 38) with silver (Ag) internal floating electrodes. A printable BMO slurry was developed and the SLB optimised to improve edge definition and burn out the binder without damaging the ceramic. The SLB increased the green strength needed for shape retention, produced crack-free parts and prevented Ag leaching into the ceramic during co-firing. The green parts were sintered after SLB in a conventional furnace at 645°C for 4 h and achieved 94.5% density, compressive strength of 4097 MPa, a relative permittivity (εr) of 33.8 and a loss tangent (tan δ) of 0.0004 (8 GHz) for BMO. The feasibility of using SLB followed by a post-printing sintering step to create BMO/Ag 3D structures was thus demonstrated

CEFLES2: the remote sensing component to quantify photosynthetic efficiency from the leaf to the region by measuring sun-induced fluorescence in the oxygen absorption bands

The CEFLES2 campaign during the Carbo Europe Regional Experiment Strategy was designed to provide simultaneous airborne measurements of solar induced fluorescence and CO2 fluxes. It was combined with extensive ground-based quantification of leaf- and canopy-level processes in support of ESA's Candidate Earth Explorer Mission of the "Fluorescence Explorer" (FLEX). The aim of this campaign was to test if fluorescence signal detected from an airborne platform can be used to improve estimates of plant mediated exchange on the mesoscale. Canopy fluorescence was quantified from four airborne platforms using a combination of novel sensors: (i) the prototype airborne sensor AirFLEX quantified fluorescence in the oxygen A and B bands, (ii) a hyperspectral spectrometer (ASD) measured reflectance along transects during 12 day courses, (iii) spatially high resolution georeferenced hyperspectral data cubes containing the whole optical spectrum and the thermal region were gathered with an AHS sensor, and (iv) the first employment of the high performance imaging spectrometer HYPER delivered spatially explicit and multi-temporal transects across the whole region. During three measurement periods in April, June and September 2007 structural, functional and radiometric characteristics of more than 20 different vegetation types in the Les Landes region, Southwest France, were extensively characterized on the ground. The campaign concept focussed especially on quantifying plant mediated exchange processes (photosynthetic electron transport, CO2 uptake, evapotranspiration) and fluorescence emission. The comparison between passive sun-induced fluorescence and active laser-induced fluorescence was performed on a corn canopy in the daily cycle and under desiccation stress. Both techniques show good agreement in detecting stress induced fluorescence change at the 760 nm band. On the large scale, airborne and ground-level measurements of fluorescence were compared on several vegetation types supporting the scaling of this novel remote sensing signal. The multi-scale design of the four airborne radiometric measurements along with extensive ground activities fosters a nested approach to quantify photosynthetic efficiency and gross primary productivity (GPP) from passive fluorescence