#COVIDisAirborne: AI-enabled multiscale computational microscopy of delta SARS-CoV-2 in a respiratory aerosol.

We seek to completely revise current models of airborne transmission of respiratory viruses by providing never-before-seen atomic-level views of the SARS-CoV-2 virus within a respiratory aerosol. Our work dramatically extends the capabilities of multiscale computational microscopy to address the significant gaps that exist in current experimental methods, which are limited in their ability to interrogate aerosols at the atomic/molecular level and thus obscure our understanding of airborne transmission. We demonstrate how our integrated data-driven platform provides a new way of exploring the composition, structure, and dynamics of aerosols and aerosolized viruses, while driving simulation method development along several important axes. We present a series of initial scientific discoveries for the SARS-CoV-2 Delta variant, noting that the full scientific impact of this work has yet to be realized.

Short single-frequency self-pulsing Brillouin-Raman distributed feedback fiber laser.

We demonstrate that the stimulated Brillouin scattering of a 250 mm long distributed feedback Raman fiber laser can self-pulse with repetition rates up to 7 MHz, pulse widths of 25 ns, and peak powers of 1.2 W. While both CW and pulsed lasing are produced from a bespoke grating at 1119 nm this laser design could be constructed at almost any wavelength, as the Raman and Brillouin gain regions are relative to the pump wavelength. The laser has a low lasing threshold for a Raman laser of 0.55 W, a peak slope efficiency of 14 %, and a maximum average output of 0.25 W. An investigation of beating between pure Raman and Raman-pumped Brillouin lasing shows that the outputs of the two processes are highly correlated and thus the Brillouin lasing is essentially single-frequency when CW and near transform limited for pulsed operation. A phenomenological model of the Raman-Brillouin interaction shows that the pulsing behaviour of such a cavity is expected and produces very similar pulsing to that the seen in experimental results.

Habitat loss, predation pressure and episodic heat-shocks interact to impact arthropods and photosynthetic functioning of microecosystems.

Ecosystems face multiple, potentially interacting, anthropogenic pressures that can modify biodiversity and ecosystem functioning. Using a bryophyte-microarthropod microecosystem we tested the combined effects of habitat loss, episodic heat-shocks and an introduced non-native apex predator on ecosystem function (chlorophyll fluorescence as an indicator of photosystem II function) and microarthropod communities (abundance and body size). The photosynthetic function was degraded by the sequence of heat-shock episodes, but unaffected by microecosystem patch size or top-down pressure from the introduced predator. In small microecosystem patches without the non-native predator, Acari abundance decreased with heat-shock frequency, while Collembola abundance increased. These trends disappeared in larger microecosystem patches or when predators were introduced, although Acari abundance was lower in large patches that underwent heat-shocks and were exposed to the predator. Mean assemblage body length (Collembola) was reduced independently in small microecosystem patches and with greater heat-shock frequency. Our experimental simulation of episodic heatwaves, habitat loss and non-native predation pressure in microecosystems produced evidence of individual and potentially synergistic and antagonistic effects on ecosystem function and microarthropod communities. Such complex outcomes of interactions between multiple stressors need to be considered when assessing anthropogenic risks for biota and ecosystem functioning.

Metabolic rejuvenation upgrades circulatory functions of red blood cells stored under blood bank conditions.

BACKGROUND: Red blood cells (RBC) change upon hypothermic conservation, and storage for 6 weeks is associated with the short-term clearance of 15% to 20% of transfused RBCs. Metabolic rejuvenation applied to RBCs before transfusion replenishes energetic sources and reverses most storage-related alterations, but how it impacts RBC circulatory functions has not been fully elucidated. STUDY DESIGN AND METHODS: Six RBC units stored under blood bank conditions were analyzed weekly for 6 weeks and rejuvenated on Day 42 with an adenine-inosine-rich solution. Impact of storage and rejuvenation on adenosine triphosphate (ATP) levels, morphology, accumulation of storage-induced microerythrocytes (SMEs), elongation under an osmotic gradient (by LORRCA), hemolysis, and phosphatidylserine (PS) exposure was evaluated. The impact of rejuvenation on filterability and adhesive properties of stored RBCs was also assessed. RESULTS: Rejuvenation of RBCs restored intracellular ATP to almost normal levels and decreased the PS exposure from 2.78% to 0.41%. Upon rejuvenation, the proportion of SME dropped from 28.2% to 9.5%, while the proportion of normal-shaped RBCs (discocytes and echinocytes 1) increased from 47.7% to 67.1%. In LORCCA experiments, rejuvenation did not modify the capacity of RBCs to elongate and induced a reduction in cell volume. In functional tests, rejuvenation increased RBC filterability in a biomimetic splenic filter (+16%) and prevented their adhesion to endothelial cells (-87%). CONCLUSION: Rejuvenation reduces the proportion of morphologically altered and adhesive RBCs that accumulate during storage. Along with the improvement in their filterability, these data show that rejuvenation improves RBC properties related to their capacity to persist in circulation after transfusion.

High power 739 nm VECSELs for future Yb+ ion cooling.

We present an operational characterization of a vertical-external-cavity surface-emitting laser emitting around 739 nm with over 150 mW in a single fundamental spatial mode. Results show that the laser is capable of oscillating on a single cavity axial mode at 740 nm for up to 22 mW. Tuning of the optical emission is shown to reach 737.3 nm. Furthermore, at best performance, the laser exhibits a slope efficiency of 8.3% and a threshold power of 1.27 W for an output coupler reflectivity of 98%.

CW demonstration of SHG spectral narrowing in a PPLN waveguide generating 2.5 W at 780†nm.

Periodically poled lithium niobate (PPLN) waveguides are a proven and popular means for efficient wavelength conversion. However, conventional PPLN waveguides typically have small mode field diameters (MFD) (≲6 µm) or significant insertion and/or propagation losses, limiting their ability to operate at multi-watt power levels. In this work we utilise zinc indiffused PPLN ridge waveguides that have a larger MFD, favourable pump/SHG modal overlap, and low insertion losses. Here for the first time, we have demonstrated continuous wave (CW) spectral narrowing from a PPLN waveguide, both with high efficiency and multi-watt second harmonic generation (SHG). 2.5 W of 780 nm has been produced by SHG of an amplified 1560 nm telecom laser with a device efficiency of 58% in a 4.0-cm long ridge waveguide. We have modelled conversion efficiency and applied experimentally measured waveguide parameters to show excellent agreement to the SHG spectra. Spectral narrowing of the full width half maximum (FWHM) of 35.7% has been measured as the nonlinear drive is increased. This work demonstrates that single-pass, multi-watt, CW SHG at 780 nm is feasible from our PPLN waveguide in the large conversion regime.

Upconversion detection of 1.25 Gb/s mid-infrared telecommunications using a silicon avalanche photodiode.

With an ever-increasing interest in secure and reliable free-space optical communication, upconversion detectors enabled through nonlinear optical processes are an attractive route to transmitting data as a mid-infrared signal. This spectral region is known to have a higher transmissivity through the atmosphere. In this work, we present an upconversion scheme for detection in the silicon absorption band using magnesium-oxide doped periodically poled lithium niobate to generate 21 mW of a 3.4 µm signal from commercial laser sources using a difference frequency generation process. Following a further nonlinear frequency conversion, via sum-frequency generation, the resulting signal at 809 nm is detected. We achieve >50 µW of signal and bit error rates of 10-7 from a single-pass nonlinear conversion for both the transmitter and receiver systems without the need for additional optical amplifiers at the receiving end. The error rates due to potentially reduced laser powers at the receiver end are investigated and laser noise transfer through our system is discussed.

Heterogeneous parallelization and acceleration of molecular dynamics simulations in GROMACS.

The introduction of accelerator devices such as graphics processing units (GPUs) has had profound impact on molecular dynamics simulations and has enabled order-of-magnitude performance advances using commodity hardware. To fully reap these benefits, it has been necessary to reformulate some of the most fundamental algorithms, including the Verlet list, pair searching, and cutoffs. Here, we present the heterogeneous parallelization and acceleration design of molecular dynamics implemented in the GROMACS codebase over the last decade. The setup involves a general cluster-based approach to pair lists and non-bonded pair interactions that utilizes both GPU and central processing unit (CPU) single instruction, multiple data acceleration efficiently, including the ability to load-balance tasks between CPUs and GPUs. The algorithm work efficiency is tuned for each type of hardware, and to use accelerators more efficiently, we introduce dual pair lists with rolling pruning updates. Combined with new direct GPU-GPU communication and GPU integration, this enables excellent performance from single GPU simulations through strong scaling across multiple GPUs and efficient multi-node parallelization.

Zinc-indiffused MgO:PPLN waveguides for blue/UV generation via VECSEL pumping.

We present the design and characterization of a zinc-indiffused periodically poled lithium-niobate ridge waveguide for second-harmonic generation of ∼390nm light from 780 nm. We use a newly developed, broadband near-infrared vertical external-cavity surface-emitting laser (VECSEL) to investigate the potential for lower-footprint nonlinear optical pump sources as an alternative to larger commercial laser systems. We demonstrate a VECSEL with an output power of 500 mW, containing an intracavity birefringent filter for spectral narrowing and wavelength selection. In this first demonstration of using a VECSEL to pump a nonlinear waveguide, we present the ability to generate 1 mW of ∼390nm light with further potential for increased efficiency and size reduction.

ZnO indiffused MgO:PPLN ridge waveguides.

We have demonstrated the first MgO:PPLN ridge waveguides based on ZnO indiffusion and dicing. The fabrication process utilizes ductile regime dicing of a planar waveguide layer producing second harmonic generation (SHG) devices with a near-symmetric sinc2 spectral profile, indicating highly uniform 40 mm long devices. A near circular pump mode is also obtained enabling efficient coupling to single mode telecommunication fibers. A conversion efficiency of 145%/W, for 1560-780 nm SHG, has been measured.

Metabolic impact of red blood cell exchange with rejuvenated red blood cells in sickle cell patients.

BACKGROUND: Red blood cell exchange (RCE) transfusions are a mainstay in the treatment of sickle cell anemia (SCA), and allow a temporary restoration of physiological parameters with respect to erythrocyte oxygen carrying capacity and systems metabolism. Recently, we noted that 1) RCE significantly impacts recipients' metabolism in SCA; 2) fresh and end-of-storage red blood cell (RBC) units differently impact systems of metabolism in healthy autologous recipients; and 3) phosphate/inosine/pyruvate/adenine (PIPA) solution reverses the metabolic age of stored RBCs. Therefore, we hypothesized that RCE with PIPA-treated RBC units could further increase the metabolic benefits of RCE in SCA patients. STUDY DESIGN AND METHODS: Circulating plasma and erythrocytes were collected from patients with SCA before and after RCE, with either conventional or PIPA-treated RBC units, prior to metabolomics analyses. RESULTS: Consistent with prior work, RCE significantly decreased circulating levels of markers of systemic hypoxemia (lactate, succinate) and decreased plasma levels of acyl-carnitines and amino acids. However, PIPA-treated exchanges were superior to untreated RCEs, with a higher energy state and an increased capacity to activate the pentose phosphate pathway and glutamine metabolism. In addition, RBCs and plasma from recipients of PIPA-treated RBC units resulted in significantly decreased levels of post-transfusion plasticizers, though at the expense of higher circulating levels of oxidized purines (hypoxanthine, xanthine, and the antioxidant urate). CONCLUSION: Transfusion of PIPA-treated RBCs further increases the metabolic benefits of RCE to patients with SCA, significantly reducing the levels of post-transfusion plasticizers.

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.

Increased fire severity alters initial vegetation regeneration across Calluna-dominated ecosystems.

Calluna vulgaris-dominated habitats are valued for ecosystem services such as carbon storage and for their conservation importance. Climate and environmental change are altering their fire regimes. In particular, more frequent summer droughts will result in higher severity wildfires. This could alter the plant community composition of Calluna habitats and thereby influence ecosystem function. To study the effect of fire severity on community composition we used rain-out shelters to simulate drought prior to experimental burns at two Calluna-dominated sites, a raised bog and a heathland. We analysed species abundance in plots surveyed ca. 16 months after fire in relation to burn severity (indicated by fire-induced soil heating). We found that fire severity was an important control on community composition at both sites. Higher fire severity increased the abundance of ericoids, graminoids and acrocarpous mosses, and decreased the abundance of pleurocarpous mosses compared to lower severity fires. At the raised bog, the keystone species Sphagnum capillifolium and Eriophorum vaginatum showed no difference in regeneration with fire severity. Species and plant functional type beta-diversity increased following fire, and was similar in higher compared to lower severity burns. Our results further our understanding of the response of Calluna-dominated habitats to projected changes in fire regimes, and can assist land managers using prescribed fires in selecting burning conditions to achieve management objectives.

Burning increases post-fire carbon emissions in a heathland and a raised bog, but experimental manipulation of fire severity has no effect.

Large amounts of carbon are stored in northern peatlands. There is concern that greater wildfire severity following projected increases in summer drought will lead to higher post-fire carbon losses. We measured soil carbon dynamics in a Calluna heathland and a raised peat bog after experimentally manipulating fire severity. A gradient of fire severity was achieved by simulating drought in 2 × 2 m plots. Ecosystem respiration (ER), net ecosystem exchange (NEE), methane (CH4) flux and concentration of dissolved organic carbon ([DOC], measured at the raised bog only) were measured for up to two years after burning. The response of these carbon fluxes to increased fire severity in drought plots was similar to plots burnt under ambient conditions associated with traditional managed burning. Averaged across all burnt plots, burning altered mean NEE from a net carbon sink at the heathland (-0.33 µmol CO2 m-2 s-1 in unburnt plots) to a carbon source (0.50 µmol m-2 s-1 in burnt plots) and at the raised bog (-0.38 and 0.16 µmol m-2 s-1, respectively). Burning also increased CH4 flux at the raised bog (from 1.16 to 25.3 nmol m-2 s-1 in the summer, when it accounted for 79% of the CO2-equivalent emission). Burning had no significant effect on soil water [DOC].

Leaky mode integrated optical fibre refractometer.

A route to monitor external refractive indices greater than the core index of the waveguide is presented. Initial application utilizes an integrated optical fibre (IOF) platform due to its potential for use in harsh environment sensing. IOF is fabricated using a bespoke flame hydrolysis deposition process to fuse an optical fibre to a planar substrate achieving an optical quality, ruggedized glass layer between the fibre and substrate was fabricated. The presented refractometer is created by direct UV writing of multiple fibre Bragg gratings into an etched (22 µm diameter) optical fibre post fabrication. Linear regression analysis is applied to quantify propagation loss by monitoring each FBG's back reflected power. The device operates with a sensitivity of approximately 350 dB/cm/RIU at a refractive index of 1.451 at 1550 nm. Numerical simulations using a transfer matrix method are presented and potential routes for development are discussed.

Evanescent field refractometry in planar optical fiber.

This Letter demonstrates a refractometer in integrated optical fiber, a new optical platform that planarizes fiber using flame hydrolysis deposition (FHD). The unique advantage of the technology is survivability in harsh environments. The platform is mechanically robust, and can survive elevated temperatures approaching 1000°C and exposure to common solvents, including acetone, gasoline, and methanol. For the demonstrated refractometer, fabrication was achieved through wet etching an SMF-28 fiber to a diameter of 8 µm before FHD planarization. An external refractive index was monitored using fiber Bragg gratings (FBGs), written into the core of the planarized fiber. A direct comparison to alternative FBG refractometers is made, for which the developed platform is shown to have comparable sensitivity, with the added advantage of survivability in harsh environments.

Metabolomics evaluation of early-storage red blood cell rejuvenation at 4°C and 37°C.

BACKGROUND: Refrigerated red blood cell (RBC) storage results in the progressive accumulation of biochemical and morphological alterations collectively referred to as the storage lesion. Storage-induced metabolic alterations can be in part reversed by rejuvenation practices. However, rejuvenation requires an incubation step of RBCs for 1 hour at 37°C, limiting the practicality of providing "on-demand," rejuvenated RBCs. We tested the hypothesis that the addition of rejuvenation solution early in storage as an adjunct additive solution would prevent-in a time window consistent with the average age of units transfused to sickle cell recipients at Duke (15 days)-many of the adverse biochemical changes that can be reversed via standard rejuvenation, while obviating the incubation step. STUDY DESIGN AND METHODS: Metabolomics analyses were performed on cells and supernatants from AS-1 RBC units (n = 4), stored for 15 days. Units were split into pediatric bag aliquots and stored at 4°C. These were untreated controls, washed with or without rejuvenation, performed under either standard (37°C) or cold (4°C) conditions. RESULTS: All three treatments removed most metabolic storage by-products from RBC supernatants. However, only standard and cold rejuvenation provided significant metabolic benefits as judged by the reactivation of glycolysis and regeneration of adenosine triphosphate and 2,3-diphosphoglycerate. Improvements in energy metabolism also translated into increased capacity to restore the total glutathione pool and regenerate oxidized vitamin C in its reduced (ascorbate) form. CONCLUSION: Cold and standard rejuvenation of 15-day-old RBCs primes energy and redox metabolism of stored RBCs, while providing a logistic advantage for routine blood bank processing workflows.

Red blood cell metabolic responses to refrigerated storage, rejuvenation, and frozen storage.

BACKGROUND: Storage of red blood cells (RBCs) under blood bank conditions promotes metabolic modulation within the RBC. This "metabolic storage lesion" may affect the quality and safety of the transfused RBCs. The aim of this study is to determine the metabolic changes in stored RBCs over 42 days of routine storage followed by a US Food and Drug Administration-approved method of rejuvenation, freezing, and preparation for transfusion. STUDY DESIGN AND METHODS: We exploited a mass spectrometry-based metabolomics approach to monitor 42-day-stored citrate phosphate dextrose/AS-1 RBCs (n = 29) that were rejuvenated, glycerolized and frozen, then thawed and deglycerolized, and held for 24 hours at 1 to 6ºC in saline-glucose. RESULTS: Previously reported metabolic alterations were confirmed in 42-day-old RBCs. In this study, in total, 181 (62%) of the biochemical compounds exhibited significant (p ≤ 0.05) change compared with Day 0 values. Rejuvenation restored adenosine triphosphate and 2,3-diphosphoglycerate levels, replenished purine reservoirs, up regulated glycolysis, increased levels of pentose phosphate pathway intermediates, and partially rescued glutathione biosynthesis. Increased levels of lysophospholipid in rejuvenated RBCs suggests the activation of recycling pathways of damaged membrane lipids, in which a total of 167 (57%) biochemical compounds showed significant change compared with Day 42 values. CONCLUSION: Rejuvenation reversed over one-half of the metabolic biochemical compounds evaluated compared with Day 42 values, and the compounds were stable through frozen storage and preparation for transfusion. Rejuvenation promoted significant metabolic reprogramming, including the reactivation of energy-generating and antioxidant pathways (the pentose phosphate pathway and glutathione homeostasis), salvage reactions, cofactor reservoirs, and membrane lipid recycling.

Leaving moss and litter layers undisturbed reduces the short-term environmental consequences of heathland managed burns.

Variation in the structure of ground fuels, i.e. the moss and litter (M/L) layer, may be an important control on fire severity in heather moorlands and thus influence vegetation regeneration and soil carbon dynamics. We completed experimental fires in a Calluna vulgaris-dominated heathland to study the role of the M/L layer in determining (i) fire-induced temperature pulses into the soil and (ii) post-fire soil thermal dynamics. Manually removing the M/L layer before burning increased fire-induced soil heating, both at the soil surface and 2 cm below. Burnt plots where the M/L layer was removed simulated the fuel structure after high severity fires where ground fuels are consumed but the soil does not ignite. Where the M/L layer was manually removed, either before or after the fire, post-fire soil thermal dynamics showed larger diurnal and seasonal variation, as well as similar patterns to those observed after wildfires, compared to burnt plots where the M/L layer was not manipulated. We used soil temperatures to explore potential changes in post-fire soil respiration. Simulated high fire severity (where the M/L layer was manually removed) increased estimates of soil respiration in warm months. With projected fire regimes shifting towards higher severity fires, our results can help land managers develop strategies to balance ecosystem services in Calluna-dominated habitats.

In pursuit of an accurate spatial and temporal model of biomolecules at the atomistic level: a perspective on computer simulation.

Despite huge advances in the computational techniques available for simulating biomolecules at the quantum-mechanical, atomistic and coarse-grained levels, there is still a widespread perception amongst the experimental community that these calculations are highly specialist and are not generally applicable by researchers outside the theoretical community. In this article, the successes and limitations of biomolecular simulation and the further developments that are likely in the near future are discussed. A brief overview is also provided of the experimental biophysical methods that are commonly used to probe biomolecular structure and dynamics, and the accuracy of the information that can be obtained from each is compared with that from modelling. It is concluded that progress towards an accurate spatial and temporal model of biomacromolecules requires a combination of all of these biophysical techniques, both experimental and computational.