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We present compelling evidence for the existence of an evolutionary adaptive response to viral agents such as SARS-CoV-2, that results in the humanin vivobiosynthesis of a family of compounds with potential antiviral activity. Using nuclear magnetic resonance (NMR) spectroscopy, we detected a characteristic spin-system motif indicative of the presence of an extended panel of urinary and serum metabolites during the acute viral phase. The structure of eight of nucleoside analogues was elucidated (six of which have not previously been reported in human urine), and subsequently confirmed by total-synthesis and matrix spiking. The molecular structures of the nucleoside analogues and their correlation with an array of serum cytokines, including IFN-α2, IFN-γ and IL-10, suggest an association with the viperin enzyme contributing to an endogenous innate immune defense mechanism against viral infection.

A JEDI NMR pulse experiment incorporating relaxational, diffusional and J-modulation peak editing has been implemented for a low field (80 MHz proton resonance frequency) spectrometer system to measure quantitatively two recently discovered plasma markers of SARS-CoV-2 infection and general inflammation. JEDI spectra capture a unique signature of two biomarker signals from acetylated glycoproteins (Glyc) and the supramolecular phospholipid composite (SPC) signals that are relatively enhanced by the combination of relaxation, diffusion and J-editing properties of the JEDI experiment that strongly attenuate contributions from the other molecular species in plasma. The SPC/Glyc ratio data were essentially identical in the 600 MHz and 80 MHz spectra obtained (R2 = 0.97) and showed significantly different ratios for control (n = 28) versus SARS-CoV-2 positive patients (n = 29) (p = 5.2 × 10-8 and 3.7 × 10-8 respectively). Simplification of the sample preparation allows for data acquisition in a similar time frame to high field machines (∼4 min) and a high-throughput version with 1 min experiment time could be feasible. These data show that these newly discovered inflammatory biomarkers can be measured effectively on low field NMR instruments that do not not require housing in a complex laboratory environment, thus lowering the barrier to clinical translation of this diagnostic technology.

Quantitative plasma lipoprotein and metabolite profiles were measured on an autonomous community of the Basque Country (Spain) cohort consisting of hospitalized COVID-19 patients (n = 72) and a matched control group (n = 75) and a Western Australian (WA) cohort consisting of (n = 17) SARS-CoV-2 positives and (n = 20) healthy controls using 600 MHz 1H nuclear magnetic resonance (NMR) spectroscopy. Spanish samples were measured in two laboratories using one-dimensional (1D) solvent-suppressed and T2-filtered methods with in vitro diagnostic quantification of lipoproteins and metabolites. SARS-CoV-2 positive patients and healthy controls from both populations were modeled and cross-projected to estimate the biological similarities and validate biomarkers. Using the top 15 most discriminatory variables enabled construction of a cross-predictive model with 100% sensitivity and specificity (within populations) and 100% sensitivity and 82% specificity (between populations). Minor differences were observed between the control metabolic variables in the two cohorts, but the lipoproteins were virtually indistinguishable. We observed highly significant infection-related reductions in high-density lipoprotein (HDL) subfraction 4 phospholipids, apolipoproteins A1 and A2,that have previously been associated with negative regulation of blood coagulation and fibrinolysis. The Spanish and Australian diagnostic SARS-CoV-2 biomarkers were mathematically and biologically equivalent, demonstrating that NMR-based technologies are suitable for the study of the comparative pathology of COVID-19 via plasma phenotyping.

We present a multivariate metabotyping approach to assess the functional recovery of nonhospitalized COVID-19 patients and the possible biochemical sequelae of "Post-Acute COVID-19 Syndrome", colloquially known as long-COVID. Blood samples were taken from patients ca. 3 months after acute COVID-19 infection with further assessment of symptoms at 6 months. Some 57% of the patients had one or more persistent symptoms including respiratory-related symptoms like cough, dyspnea, and rhinorrhea or other nonrespiratory symptoms including chronic fatigue, anosmia, myalgia, or joint pain. Plasma samples were quantitatively analyzed for lipoproteins, glycoproteins, amino acids, biogenic amines, and tryptophan pathway intermediates using Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Metabolic data for the follow-up patients (n = 27) were compared with controls (n = 41) and hospitalized severe acute respiratory syndrome SARS-CoV-2 positive patients (n = 18, with multiple time-points). Univariate and multivariate statistics revealed variable patterns of functional recovery with many patients exhibiting residual COVID-19 biomarker signatures. Several parameters were persistently perturbed, e.g., elevated taurine (p = 3.6 × 10-3 versus controls) and reduced glutamine/glutamate ratio (p = 6.95 × 10-8 versus controls), indicative of possible liver and muscle damage and a high energy demand linked to more generalized tissue repair or immune function. Some parameters showed near-complete normalization, e.g., the plasma apolipoprotein B100/A1 ratio was similar to that of healthy controls but significantly lower (p = 4.2 × 10-3) than post-acute COVID-19 patients, reflecting partial reversion of the metabolic phenotype (phenoreversion) toward the healthy metabolic state. Plasma neopterin was normalized in all follow-up patients, indicative of a reduction in the adaptive immune activity that has been previously detected in active SARS-CoV-2 infection. Other systemic inflammatory biomarkers such as GlycA and the kynurenine/tryptophan ratio remained elevated in some, but not all, patients. Correlation analysis, principal component analysis (PCA), and orthogonal-partial least-squares discriminant analysis (O-PLS-DA) showed that the follow-up patients were, as a group, metabolically distinct from controls and partially comapped with the acute-phase patients. Significant systematic metabolic differences between asymptomatic and symptomatic follow-up patients were also observed for multiple metabolites. The overall metabolic variance of the symptomatic patients was significantly greater than that of nonsymptomatic patients for multiple parameters (χ2 p = 0.014). Thus, asymptomatic follow-up patients including those with post-acute COVID-19 Syndrome displayed a spectrum of multiple persistent biochemical pathophysiology, suggesting that the metabolic phenotyping approach may be deployed for multisystem functional assessment of individual post-acute COVID-19 patients.

This paper presents a second-order voltage-controlled oscillator (VCO)-based front-end for the direct digitization of biopotential signals. This work addresses the non-linearity of VCO-based ADC architectures with a mismatch resilient, multi-phase quantizer, a gated-inverted-ring oscillator (GIRO), achieving110-dB SFDR. Leveraging the time-domain encoding of the first integrator, the ADC's power is dynamically scaled with the input amplitude enabling up to 35% power savings in the absence of motion artifacts or interference. An auxiliary input-impedance booster increases the ADC's input impedance to 50 MΩ across the entire bandwidth. Fabricated in a 65-nm CMOS process, this ADC achieves 92.3-dB SNDR in a 1 kHz BW while consuming 5.8 µW for a 174.7 dB Schreier FoM.

A conceptual model for the chemical evolution of near-field water chemistry in the proposed high-level nuclear waste repository at Yucca Mountain, Nevada is presented. This model considers the effects of differential solubility in flowing water that is subject to evaporation or condensation. The results of a simplified numerical implementation of the model are used to predict the aqueous chemistries produced from a variety of source waters under two bounding assumptions of separation. The model predicts that, under some conditions the most soluble ions will not always be present in solution. The more soluble ions may precipitate at different locations than ions of slightly less solubility leading to a highly complex system containing different brine compositions at different locations.

The present study details facile synthesis of hollow Cu2O nanospheres decorated with Ag nanoparticles using a simple surfactant technique for enhanced photocatalytic activity. The morphology and structure is studied via XRD and SEM. Cu2O hollow nanospheres with a diameter of 500-800 nm were synthesized via Ostwald ripening using CuSO4 aqueous solution. The catalytic activity of Cu2O is studied in the presence of UV and visible light using Methyl Orange (MO) as a model pollutant. Ag decorated Cu2O particles showed a 49% increase in photocatalytic activity over the undecorated Cu2O. The improved photocatalytic activity is achieved by surface plasmon resonance effects in the silver nanoparticles, allowing utilization of the lower energy portion of the solar spectrum.

During evaluation for monocular visual loss, a 48-year-old woman was found to have a posttraumatic paraophthalmic internal carotid artery (ICA) pseudoaneurysm. She underwent reconstruction of the ophthalmic segment of the right ICA with a Pipeline embolization device but her vision did not return.

Automated rendezvous and docking (AR&D) is an activity that is vital to NASA's future endeavors. A team of NASA engineers has created a test bed that allows sensor systems to be tested but also incorporates operator interfaces in order to evaluate the information required by an operator to oversee automated systems. Several sensors have been run through the test bed and more are scheduled in the future. The test bed will be described along with the operator interfaces and results of sensor testing.

The Contact Dynamics Simulation Laboratory (CDSL) of the Marshall Space Flight Center provides for refined hardware-in-the-loop real-time simulation of docking and berthing mechanisms and associated control systems. This facility is employed to verify the performance of docking/berthing mechanisms during Earth-orbit operations, determine the capture envelope of dockingherthing devices, measure contact loads at vehicle interfaces, and evaluate visual cues for man-in-the-loop operations. The CDSL has developed test verified analytical models of such systems as the ISS Common Berthing Mechanism and HST Three Point Docking Mechanism. This paper will describe the modeling and test techniques employed at the CDSL and present results from recent programs.

Purpose Patients with continuous-flow left ventricular assist devices (CF-LVAD) may develop heart failure (HF) with predominant right sided HF signs. We aimed to examine the incidence, clinical and echocardiographic predictors of late right ventricular failure (RVF). Methods and Materials Medical records and pre-implant echocardiograms of patients who received CF-LVADs from 2008-2012 at our center were reviewed. Patients who expired within 30 days of implant were excluded. RVF was defined as a syndrome of HF including leg swelling/edema and jugular venous distention requiring in- or out-patient therapy (diuresis and/or pump speed change). Multivariate logistic regression analysis was performed to determine predictors of late RVF episodes. Results A total of 165 patients were implanted with CF-LVADs of whom 140 survived 30 days post-surgery. Mean age 54, 75% men, 60% ischemic. A total of 37 patients developed RVF with a mean time to event of 216 days (range 31-927). 11 (7.8%) patients required inpatient management. Pre-implant echo parameters that predicted these events were right atrial pressure (RAP) (p=0.001) and RAP/(E/e’) ratio (p=0.002). No clinical parameters, including a history of hypertension or baseline pump speed, were predictive of late RVF ( Table ). Conclusions Late RVF after CF-LVAD implantation is not uncommon. The only pre-LVAD predictors of late RVF were echo-derived RAP and the ratio of RAP/(E/e’), surrogates of high right- relative to left-sided filling pressures.

The Segment Alignment Maintenance System (SAMs) was installed on McDonald Observatory's Hobby-Eberly Telescope (HET) in August 2001. The SAMs became fully operational in October 2001. The SAMs uses a system of 480 inductive edge sensors to correct misalignments of the HET's 91 primary mirror segments when the segments are perturbed from their aligned reference positions. A special observer estimated and corrects for the global radius of curvature (GroC) mode, a mode unobservable by the edge sensors. The SAMs edge sensor system and (GroC) estimator are able to maintain HET's primary figure for much longer durations than previously had been observed. Telescope image quality has improved, and the amount of overhead time required from primary mirror alignment has been reduced. This paper gives a functional description of the SAMs control system and presents performance verification data. This paper also describes how the SAMs has improved the operational efficiency of the HET.

A system, which estimates the global radius of curvature (GroC) and corrects for changes in GroC on a segmented primary mirror has been developed for and verified on McDonald Observatory's Hobby Eberly Telescope (HET). The GroC estimation and control system utilizes HET's primary mirror control (PMC) system and the Segment Alignment Maintenance System (SAMS), an inductive edge sensor system. A special set of boundary conditions is applied to the derivation of the optimal edge match control. The special boundary conditions allow the further derivation of an observer, which enables estimation and control of the Groc mode to within HET's specification. The magnitude of the GroC mode can then be controlled despite the inability of the SAMS edge sensor system, by itself, to observe or control the GroC mode. The observer can be extended to any segmented mirror telescope. It will be shown that the observer improves with accuracy as the number of segments increases. This paper presents the mathematical theory of the observer. Simulation results will demonstrate the inherent accuracy and robustness of the system. Performance verification data from the HET will be presented.

The software development for an upgrade to the Hobby-Eberly Telescope (HET) was done in LABView. In order to improve the performance of the HET at the McDonald Observatory, a closed-loop system had to be implemented to keep the mirror segments aligned during periods of observation. The control system, called the Segment Alignment Maintenance System (SAMs), utilized inductive sensors to measure the relative motions of the mirror segments. Software was developed in LABView to tie the sensors, operator interface, and mirror-control motors together. Developing the software in LABView allowed the system to be flexible, understandable, and able to be modified by the end users. Since LABView is built using block diagrams, the software naturally followed the designed control system's block and flow diagrams, and individual software blocks could be easily verified. LABView's many built-in display routines allowed easy visualization of diagnostic and health-monitoring data during testing. Also, since LABView is a multi-platform software package, different programmers could develop the code remotely on various types of machines. LABView s ease of use facilitated rapid prototyping and field testing. There were some unanticipated difficulties in the software development, but the use of LABView as the software "language" for the development of SAMs contributed to the overall success of the project.

NASA's Marshall Space Flight Center, in collaboration with Blue Line Engineering of Colorado Springs, Colorado, is developing a Segment Alignment Maintenance System (SAMS) for McDonald Observatory's Hobby-Eberly Telescope (HET). The SAMS shall sense motions of the 91 primary mirror segments and send corrections to HET's primary mirror controller as the mirror segments misalign due to thermo-elastic deformations of the mirror support structure. The SAMS consists of inductive edge sensors. All measurements are sent to the SAMS computer where mirror motion corrections are calculated. In October 2000, a prototype SAMS was installed on a seven-segment cluster of the HET. Subsequent testing has shown that the SAMS concept and architecture are a viable practical approach to maintaining HET's primary mirror figure, or the figure of any large segmented telescope. This paper gives a functional description of the SAMS sub-array components and presents test data to characterize the performance of the sub-array SAMS.