The Dynamic Structure of Thrombin in Solution

AbstractThe backbone dynamics of human α-thrombin inhibited at the active site serine were analyzed using R1, R2, and heteronuclear NOE experiments, variable temperature TROSY 2D [1H-15N] correlation spectra, and Rex measurements. The N-terminus of the heavy chain, which is formed upon zymogen activation and inserts into the protein core, is highly ordered, as is much of the double beta-barrel core. Some of the surface loops, by contrast, remain very dynamic with order parameters as low as 0.5 indicating significant motions on the ps-ns timescale. Regions of the protein that were thought to be dynamic in the zymogen and to become rigid upon activation, in particular the γ-loop, the 180s loop, and the Na+ binding site have order parameters below 0.8. Significant Rex was observed in most of the γ-loop, in regions proximal to the light chain, and in the β-sheet core. Accelerated molecular dynamics simulations yielded a molecular ensemble consistent with measured residual dipolar couplings that revealed dynamic motions up to milliseconds. Several regions, including the light chain and two proximal loops, did not appear highly dynamic on the ps-ns timescale, but had significant motions on slower timescales

"Knees" in lithium-ion battery aging trajectories

Lithium-ion batteries can last many years but sometimes exhibit rapid, nonlinear degradation that severely limits battery lifetime. In this work, we review prior work on "knees" in lithium-ion battery aging trajectories. We first review definitions for knees and three classes of "internal state trajectories" (termed snowball, hidden, and threshold trajectories) that can cause a knee. We then discuss six knee "pathways", including lithium plating, electrode saturation, resistance growth, electrolyte and additive depletion, percolation-limited connectivity, and mechanical deformation -- some of which have internal state trajectories with signals that are electrochemically undetectable. We also identify key design and usage sensitivities for knees. Finally, we discuss challenges and opportunities for knee modeling and prediction. Our findings illustrate the complexity and subtlety of lithium-ion battery degradation and can aid both academic and industrial efforts to improve battery lifetime.Comment: Submitted to the Journal of the Electrochemical Societ

Probing the Interstellar Medium in Early type galaxies with ISO observations

Four IRAS-detected early type galaxies were observed with ISO. With the exception of the 15 micron image of NGC1052, the mid-IR emission from NGC1052, NGC1155, NGC5866 and NGC6958 at 4.5, 7 and 15 microns show extended emission. Mid-IR emission from NGC1052, NGC1155, and NGC6958 follows a de Vaucouleurs profile. The ratio of 15/7 micron flux decreases with radius in these galaxies, approaching the values empirically observed for purely stellar systems. In NGC5866, the 7 and 15 micron emission is concentrated in the edge-on dust lane. All the galaxies are detected in the [CII] line, and the S0s NGC1155 and NGC5866 are detected in the [OI] line as well. The ISO-LWS observations of the [CII] line are more sensitive measures of cool, neutral ISM than HI and CO by about a factor of 10-100. Three of four early type galaxies, namely NGC1052, NGC6958 and NGC5866, have low ratio FIR/Blue and show a lower [CII]/FIR, which is due to a softer radiation field from old stellar populations. The low [CII]/CO ratio in NGC5866 ([CII]/CO(1-0) < 570) confirms this scenario. We estimate the UV radiation expected from the old stellar populations in these galaxies and compare it to that needed to heat the gas to account for the cooling observed [CII] and [OI] lines. In three out of four galaxies, NGC1052, NGC5866 and NGC6958, the predicted UV radiation falls short by a factor of 2-3. In view of the observed intrinsic scatter in the "UV-upturn" in elliptical galaxies and its great sensitivity to age and metallicity effects, this is not significant. However, the much larger difference (about a factor of 20) between the UV radiation from old stars and that needed to produce the FIR lines for NGC 1155 is strong evidence for the presence of young stars, in NGC1155.Comment: To appear in the Astrophysical Journal. Figure 1 appears as a separate jpg figur

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Cruciferous vegetable supplementation in a controlled diet study alters the serum peptidome in a GSTM1-genotype dependent manner

<p>Abstract</p> <p>Background</p> <p>Cruciferous vegetable intake is inversely associated with the risk of several cancers. Isothiocyanates (ITC) are hypothesized to be the major bioactive constituents contributing to these cancer-preventive effects. The polymorphic glutathione-<it>S</it>-transferase (GST) gene family encodes several enzymes which catalyze ITC degradation <it>in vivo</it>.</p> <p>Methods</p> <p>We utilized high throughput proteomics methods to examine how human serum peptides (the "peptidome") change in response to cruciferous vegetable feeding in individuals of different <it>GSTM1 </it>genotypes. In two randomized, crossover, controlled feeding studies (EAT and 2EAT) participants consumed a fruit- and vegetable-free basal diet and the basal diet supplemented with cruciferous vegetables. Serum samples collected at the end of the feeding period were fractionated and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry spectra were obtained. Peak identification/alignment computer algorithms and mixed effects models were used to analyze the data.</p> <p>Results</p> <p>After analysis of spectra from EAT participants, 24 distinct peaks showed statistically significant differences associated with cruciferous vegetable intake. Twenty of these peaks were driven by their <it>GSTM1 </it>genotype (i.e., <it>GSTM1+ </it>or <it>GSTM1- </it>null). When data from EAT and 2EAT participants were compared by joint processing of spectra to align a common set, 6 peaks showed consistent changes in both studies in a genotype-dependent manner. The peaks at 6700 <it>m/z </it>and 9565 <it>m/z </it>were identified as an isoform of transthyretin (TTR) and a fragment of zinc α2-glycoprotein (ZAG), respectively.</p> <p>Conclusions</p> <p>Cruciferous vegetable intake in <it>GSTM1+ </it>individuals led to changes in circulating levels of several peptides/proteins, including TTR and a fragment of ZAG. TTR is a known marker of nutritional status and ZAG is an adipokine that plays a role in lipid mobilization. The results of this study present evidence that the <it>GSTM1</it>-genotype modulates the physiological response to cruciferous vegetable intake.</p

Frequency drift in MR spectroscopy at 3T

Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B-0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.Method: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC).Results: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p &lt; 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI.Discussion: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.</p

The re-discovery of contemplation through science : with Tom McLeish, “The Re-Discovery of Contemplation through Science: Boyle Lecture 2021”; Rowan Williams, “The Re-Discovery of Contemplation through Science: A Response to Tom McLeish”; Fraser Watts, “Discussion of the Boyle Lecture 2021”; and Tom McLeish, “Response to Boyle Lecture 2021 Panel and Participant Discussion.”

Some of the early-modern changes in the social framing of science, while often believed to be essential, are shown to be contingent. They contribute to the flawed public narrative around science today, and especially to the misconceptions around science and religion. Four are examined in detail, each of which contributes to the demise of the contemplative stance that science both requires and offers. They are: (1) a turn from an immersed subject to the pretense of a pure objectivity, (2) a turn from imagination as a legitimate pathway to knowledge, (3) a turn from shared and participative science to a restricted professionalism, and (4) an overprosaic reading of the metaphor of the “Book of Nature.” All four, but especially the imperative to consider reading nature as poetry, and a deeper examination of the entanglements between poetry and theoretical science, draw unavoidably on theological ideas, and contribute to a developing “theology of science.”