Metabolically exaggerated cardiac reactions to acute psychological stress: The effects of resting blood pressure status and possible underlying mechanisms

The study aimed to: confirm that acute stress elicits metabolically exaggerated increases in cardiac activity; test whether individuals with elevated resting blood pressure show more exaggerated cardiac reactions to stress than those who are clearly normotensive; and explore the underlying mechanisms. Cardiovascular activity and oxygen consumption were measured pre-, during, and post- mental stress, and during graded submaximal cycling exercise in 11 young men with moderately elevated resting blood pressure and 11 normotensives. Stress provoked increases in cardiac output that were much greater than would be expected from contemporary levels of oxygen consumption. Exaggerated cardiac reactions were larger in the relatively elevated blood pressure group. They also had greater reductions in total peripheral resistance, but not heart rate variability, implying that their more exaggerated cardiac reactions reflected greater β-adrenergic activation

3‘-Phosphoadenosine-5‘-phosphosulfate Reductase in Complex with Thioredoxin: A Structural Snapshot in the Catalytic Cycle

The crystal structure of Escherichia coli 3‘-phosphoadenosine-5‘-phosphosulfate (PAPS) reductase in complex with E. coli thioredoxin 1 (Trx1) has been determined to 3.0 Å resolution. The two proteins are covalently linked via a mixed disulfide that forms during nucleophilic attack of Trx's N-terminal cysteine on the Sγ atom of the PAPS reductase S-sulfocysteine (E-Cys-Sγ-SO_3^-), a central intermediate in the catalytic cycle. For the first time in a crystal structure, residues 235−244 in the PAPS reductase C-terminus are observed, depicting an array of interprotein salt bridges between Trx and the strictly conserved glutathione-like sequence, Glu^(238)Cys^(239)Gly^(240)Leu^(241)His^(242). The structure also reveals a Trx-binding surface adjacent to the active site cleft and regions of PAPS reductase associated with conformational change. Interaction at this site strategically positions Trx to bind the S-sulfated C-terminus and addresses the mechanism for requisite structural rearrangement of this domain. An apparent sulfite-binding pocket at the protein−protein interface explicitly orients the S-sulfocysteine Sγ atom for nucleophilic attack in a subsequent step. Taken together, the structure of PAPS reductase in complex with Trx highlights the large structural rearrangement required to accomplish sulfonucleotide reduction and suggests a role for Trx in catalysis beyond the paradigm of disulfide reduction

The geometry of thermodynamic control

A deeper understanding of nonequilibrium phenomena is needed to reveal the principles governing natural and synthetic molecular machines. Recent work has shown that when a thermodynamic system is driven from equilibrium then, in the linear response regime, the space of controllable parameters has a Riemannian geometry induced by a generalized friction tensor. We exploit this geometric insight to construct closed-form expressions for minimal-dissipation protocols for a particle diffusing in a one dimensional harmonic potential, where the spring constant, inverse temperature, and trap location are adjusted simultaneously. These optimal protocols are geodesics on the Riemannian manifold, and reveal that this simple model has a surprisingly rich geometry. We test these optimal protocols via a numerical implementation of the Fokker-Planck equation and demonstrate that the friction tensor arises naturally from a first order expansion in temporal derivatives of the control parameters, without appealing directly to linear response theory

Statistical Comparison of the Baseline Mechanical Properties of NBG-18 and PCEA Graphite

High-purity graphite is the core structural material of choice in the Very High Temperature Reactor (VHTR), a graphite-moderated, helium-cooled design that is capable of producing process heat for power generation and for industrial process that require temperatures higher than the outlet temperatures of present nuclear reactors. The Baseline Graphite Characterization Program is endeavoring to minimize the conservative estimates of as-manufactured mechanical and physical properties by providing comprehensive data that captures the level of variation in measured values. In addition to providing a comprehensive comparison between these values in different nuclear grades, the program is also carefully tracking individual specimen source, position, and orientation information in order to provide comparisons and variations between different lots, different billets, and different positions from within a single billet. This report is a preliminary comparison between the two grades of graphite that were initially favored in the two main VHTR designs. NBG-18, a medium-grain pitch coke graphite from SGL formed via vibration molding, was the favored structural material in the pebble-bed configuration, while PCEA, a smaller grain, petroleum coke, extruded graphite from GrafTech was favored for the prismatic configuration. An analysis of the comparison between these two grades will include not only the differences in fundamental and statistically-significant individual strength levels, but also the differences in variability in properties within each of the grades that will ultimately provide the basis for the prediction of in-service performance. The comparative performance of the different types of nuclear grade graphites will continue to evolve as thousands more specimens are fully characterized from the numerous grades of graphite being evaluated

Benchmarking Quantum Processor Performance at Scale

As quantum processors grow, new performance benchmarks are required to capture the full quality of the devices at scale. While quantum volume is an excellent benchmark, it focuses on the highest quality subset of the device and so is unable to indicate the average performance over a large number of connected qubits. Furthermore, it is a discrete pass/fail and so is not reflective of continuous improvements in hardware nor does it provide quantitative direction to large-scale algorithms. For example, there may be value in error mitigated Hamiltonian simulation at scale with devices unable to pass strict quantum volume tests. Here we discuss a scalable benchmark which measures the fidelity of a connecting set of two-qubit gates over $N$ qubits by measuring gate errors using simultaneous direct randomized benchmarking in disjoint layers. Our layer fidelity can be easily related to algorithmic run time, via $\gamma$ defined in Ref.\cite{berg2022probabilistic} that can be used to estimate the number of circuits required for error mitigation. The protocol is efficient and obtains all the pair rates in the layered structure. Compared to regular (isolated) RB this approach is sensitive to crosstalk. As an example we measure a $N=80~(100)$ qubit layer fidelity on a 127 qubit fixed-coupling "Eagle" processor (ibm\_sherbrooke) of 0.26(0.19) and on the 133 qubit tunable-coupling "Heron" processor (ibm\_montecarlo) of 0.61(0.26). This can easily be expressed as a layer size independent quantity, error per layered gate (EPLG), which is here $1.7\times10^{-2}(1.7\times10^{-2})$ for ibm\_sherbrooke and $6.2\times10^{-3}(1.2\times10^{-2})$ for ibm\_montecarlo.Comment: 15 pages, 8 figures (including appendices

The Mechanical Properties of Individual, Electrospun Fibrinogen Fibers

We used a combined atomic force microscope (AFM)/fluorescence microscope technique to study the mechanical properties of individual, electrospun fibrinogen fibers in aqueous buffer. Fibers (average diameter 208 nm) were suspended over 12 μm-wide grooves in a striated, transparent substrate. The AFM, situated above the sample, was used to laterally stretch the fibers and to measure the applied force. The fluorescence microscope, situated below the sample, was used to visualize the stretching process. The fibers could be stretched to 2.3 times their original length before breaking; the breaking stress was 22·106 Pa. We collected incremental stress-strain curves to determine the viscoelastic behavior of these fibers. The total stretch modulus was 16·106 Pa and the relaxed, elastic modulus was 6.7·106 Pa. When held at constant strain, electrospun fibrinogen fibers showed a fast and slow stress relaxation time of 3 and 56 seconds. Our fibers were spun from the typically used 90% 1,1,1,3,3,3-hexafluoro-2-propanol (90-HFP) electrospinning solution and resuspended in aqueous buffer. Circular dichroism spectra indicate that alpha-helical content of fibrinogen is ~70% higher in 90-HFP than in aqueous solution. These data are needed to understand the mechanical behavior of electrospun fibrinogen structures. Our technique is also applicable to study other, nanoscopic fibers

Baseline Graphite Characterization: First Billet

The Next Generation Nuclear Plant Project Graphite Research and Development program is currently establishing the safe operating envelope of graphite core components for a very high temperature reactor design. To meet this goal, the program is generating the extensive amount of quantitative data necessary for predicting the behavior and operating performance of the available nuclear graphite grades. In order determine the in-service behavior of the graphite for the latest proposed designs, two main programs are underway. The first, the Advanced Graphite Creep (AGC) program, is a set of experiments that are designed to evaluate the irradiated properties and behavior of nuclear grade graphite over a large spectrum of temperatures, neutron fluences, and compressive loads. Despite the aggressive experimental matrix that comprises the set of AGC test runs, a limited amount of data can be generated based upon the availability of space within the Advanced Test Reactor and the geometric constraints placed on the AGC specimens that will be inserted. In order to supplement the AGC data set, the Baseline Graphite Characterization program will endeavor to provide supplemental data that will characterize the inherent property variability in nuclear-grade graphite without the testing constraints of the AGC program. This variability in properties is a natural artifact of graphite due to the geologic raw materials that are utilized in its production. This variability will be quantified not only within a single billet of as-produced graphite, but also from billets within a single lot, billets from different lots of the same grade, and across different billets of the numerous grades of nuclear graphite that are presently available. The thorough understanding of this variability will provide added detail to the irradiated property data, and provide a more thorough understanding of the behavior of graphite that will be used in reactor design and licensing. This report covers the development of the Baseline Graphite Characterization program from a testing and data collection standpoint through the completion of characterization on the first billet of nuclear-grade graphite. This data set is the starting point for all future evaluations and comparisons of material properties

Asymptomatic Seroconversion of Immunoglobulins to SARS-CoV-2 in a Pediatric Dialysis Unit

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Dialysis units are at especially high risk of infectious disease transmission, and concern exists about spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Dialysis units in Wuhan, China, have reported high coronavirus disease 2019 (COVID-19) prevalence, due in part to unique exposure challenges that limit social distancing efforts, including open bay formats and rotating/multiple nursing assignments. This study describes SARS-CoV-2 seroconversion in patients and health care workers in a pediatric dialysis unit.The study was supported by the Lilly Endowment Inc. Physician Scientist Initiative to Drs. Hains and Schwaderer. Dr. Krammer was supported by institutional seed funding

The metabolic syndrome adds utility to the prediction of mortality over its components: The Vietnam Experience Study

Background\ud The metabolic syndrome increases mortality risk. However, as “non-affected” individuals may still have up to two risk factors, the utility of using three or more components to identify the syndrome, and its predictive advantage over individual components have yet to be determined.\ud \ud Methods\ud Participants, male Vietnam-era veterans (n = 4265) from the USA, were followed-up from 1985/1986 for 14.7 years (61,498 person-years), and all-cause and cardiovascular disease deaths collated. Cox's proportional-hazards regression was used to assess the effect of the metabolic syndrome and its components on mortality adjusting for a wide range of potential confounders.\ud \ud Results\ud At baseline, 752 participants (17.9%) were identified as having metabolic syndrome. There were 231 (5.5%) deaths from all-causes, with 60 from cardiovascular disease. After adjustment for a range of covariates, the metabolic syndrome increased the risk of all-cause, HR 2.03, 95%CI 1.52, 2.71, and cardiovascular disease mortality, HR 1.92, 95%CI 1.10, 3.36. Risk increased dose-dependently with increasing numbers of components. The increased risk from possessing only one or two components was not statistically significant. The adjusted risk for four or more components was greater than for only three components for both all-cause, HR 2.30, 95%CI 1.45, 3.66 vs. HR 1.70, 95%CI 1.11, 2.61, and cardiovascular disease mortality, HR 3.34, 95%CI 1.19, 9.37 vs. HR 2.81, 95%CI 1.07, 7.35. The syndrome was more informative than the individual components for all-cause mortality, but could not be assessed for cardiovascular disease mortality due to multicollinearity. Hyperglycaemia was the individual strongest parameter associated with mortality.\ud \u