How to Reduce Tire-Pavement Noise: Interim Better Practices for Constructing and Texturing Concrete Pavement Surfaces

This report describes better practices for constructing and texturing quieter concrete pavements; better practices that answer the question of how we can reduce tire-pavement noise; and better practices that don\u27t compromise the other things about the pavement that are of equal or greater importance, including safety, cost, and durability. In developing this document, the National Concrete Pavement Technology Center at Iowa State University draws from its decades of combined experience working for and alongside concrete paving contractors. This document also includes the collective experience of various contractors and equipment manufacturers with a reputation for quality. These guidelines further address the challenges that are faced in consistently producing a high-quality product in a low-bid environment. This document is intended to serve as interim guidelines and better practices for texturing. Work under the pooled fund study that sponsored the development of this document is ongoing. Additional data are being collected on both existing and new concrete paving projects that will validate the practices described herein. Given the importance of this issue, however, it is believed that many of these practices can be implemented immediately without adverse consequences. Refinements to these practices can then be implemented as necessary as changes to these better practices are made in the near future

Acute vs. Chronic Citrulline Malate Supplementation on Muscle Fatigue

Citrulline malate has been proposed to aid in reducing fatigue by increasing blood flow through promoting an increase in the nitric oxide synthase pathway along with the ability to remove ammonia and lactate accumulations. Results on the effectiveness of an acute supplementation are mixed, but it is proposed that regular consumption may help to attenuate the onset of fatigue during exercise. PURPOSE: To investigate the effects of acute and chronic citrulline malate supplementation on fatigue rate of the quadriceps. METHODS: Recreationally trained males (n=18, 24±5 yr, 83±14 kg, 174±6 cm) participated in seven testing sessions. The familiarization session consisted of participants performing a graded exercise test to determine max power output. In a randomized, counterbalanced order, participants consumed a placebo (PL) and citrulline malate (CM) treatment for two separate dosing periods. For each dosing period, participants reported on three separate days with seven days between each visit. The first experimental testing session for each dosing period was considered the baseline day (BL), the second session the acute day (D1), and the third session the chronic day (D2). For chronic supplementation, all participants consumed each treatment for seven consecutive days. The exercise protocol all testing sessions and the four supplemental testing sessions included exercising on a cycle ergometer at 50-60% of their max power output for 30 min. Following the bout, all participants performed the Thorstensson test on an isokinetic dynamometer for torque, power, and fatigue rate of the dominate leg quadriceps. RESULTS: The acute supplement x time interactions were not significant (p\u3e0.05) for peak power (PL BL 469+81 W, PL D1 490+97 W vs. CM BL 465+85 W, CM D1 480+103 W), peak torque (PL BL 150+26 Nm, PL D1 157+32 Nm vs. CM BL 149+26 Nm, CM D1 156+33 Nm), fatigue rate (PL BL 57+9%, PL D1 57+10% vs. CM BL 57+10%, CM D1 56+9%), and heart rate (PL BL 156+17 bpm, PL D1 146+13 bpm vs. CM BL 155+11 bpm, CM D1 146+11 bpm). The chronic supplement x time interactions were not significant (p\u3e0.05) for peak power (PL BL 469+81 W, PL D2 501+99 W vs. CM BL 464+85 W, CM D2 501+81 W), peak torque (PL BL 150+26 Nm, PL D2 161+31 Nm vs. CM BL 149+27 Nm, CM D2 161+26 Nm), fatigue rate (PL BL 57+9%, PL D2 58+9% vs. CM BL 57+10%, CM D2 58+9%), and heart rate (PL BL 156+17 bpm, PL D2 146+9 bpm vs. CM BL 155+11 bpm, CM D2 146+9 bpm). CONCLUSION: The results of this study suggest that neither acute or chronic supplementation of CM had an effect on recovery or fatigue rate of the quadriceps. Based on the data collected there were no significant differences between the recorded values for torque and power for each participant

Water-Mediated Carbon–Oxygen Hydrogen Bonding Facilitates S-Adenosylmethionine Recognition in the Reactivation Domain of Cobalamin-Dependent Methionine Synthase

The C-terminal domain of cobalamin-dependent methionine synthase (MetH) has an essential role in catalyzing the reactivation of the enzyme following the oxidation of its cobalamin cofactor. This reactivation occurs through reductive methylation of the cobalamin using S-adenosylmethionine (AdoMet) as the methyl donor. Herein, we examine the molecular recognition of AdoMet by the MetH reactivation domain utilizing structural, biochemical, and computational approaches. Crystal structures of the Escherichia coli MetH reactivation domain in complex with AdoMet, the methyl transfer product S-adenosylhomocysteine (AdoHcy), and the AdoMet analogue inhibitor sinefungin illustrate that the ligands exhibit an analogous conformation within the solvent-exposed substrate binding cleft of the enzyme. AdoMet binding is stabilized by an intramolecular sulfur–oxygen chalcogen bond between the sulfonium and carboxylate groups of the substrate and by water-mediated carbon–oxygen hydrogen bonding between the sulfonium cation and the side chains of Glu1097 and Glu1128 that bracket the substrate binding cleft. AdoMet and sinefungin exhibited similar binding affinities for the MetH reactivation domain, whereas AdoHcy displayed an affinity for the enzyme that was an order of magnitude lower. Mutations of Glu1097 and Glu1128 diminished the AdoMet/AdoHcy binding selectivity ratio to approximately 2-fold, underscoring the role of these residues in enabling the enzyme to discriminate between the substrate and product. Together, these findings indicate that Glu1097 and Glu1128 in MetH promote high-affinity recognition of AdoMet and that sinefungin and potentially other AdoMet-based methyltransferase inhibitors can abrogate MetH reactivation, which would result in off-target effects associated with alterations in methionine homeostasis and one-carbon metabolism

Structural and Functional Characterization of Sulfonium Carbon-Oxygen Hydrogen Bonding in the Deoxyamino Sugar Methyltransferase TyIM1

The N-methyltransferase TylM1 from Streptomyces fradiae catalyzes the final step in the biosynthesis of the deoxyamino sugar mycaminose, a substituent of the antibiotic tylosin. The high-resolution crystal structure of TylM1 bound to the methyl donor S-adenosylmethionine (AdoMet) illustrates a network of carbon-oxygen (CH•••O) hydrogen bonds between the substrate’s sulfonium cation and residues within the active site. These interactions include hydrogen bonds between the methyl and methylene groups of the AdoMet sulfonium cation and the hydroxyl groups of Tyr14 and Ser120 in the enzyme. To examine the functions of these interactions, we generated Tyr14 to phenylalanine (Y14F) and Ser120 to alanine (S120A)mutations to selectively ablate the CH•••O hydrogen bonding to AdoMet. The TylM1 S120A mutant exhibited a modest decrease in the catalytic efficiency relative to wild type (WT) enzyme, whereas the Y14F mutation resulted in an approximately 30-fold decrease in catalytic efficiency. In contrast, site-specific substitution of Tyr14 by the noncanonical amino acid p-aminophenylalanine partially restored activity comparable to the WT enzyme. Correlatively, quantum mechanical calculations of the activation barrier energies of WT TylM1 and the Tyr14 mutants suggest that substitutions which abrogate hydrogen bonding with the AdoMet methyl group impair methyl transfer. Together, these results offer insights into roles of CH•••O hydrogen bonding in modulating the catalytic efficiency of TylM1

A High Statistics Search for Ultra-High Energy Gamma-Ray Emission from Cygnus X-3 and Hercules X-1

We have carried out a high statistics (2 Billion events) search for ultra-high energy gamma-ray emission from the X-ray binary sources Cygnus X-3 and Hercules X-1. Using data taken with the CASA-MIA detector over a five year period (1990-1995), we find no evidence for steady emission from either source at energies above 115 TeV. The derived upper limits on such emission are more than two orders of magnitude lower than earlier claimed detections. We also find no evidence for neutral particle or gamma-ray emission from either source on time scales of one day and 0.5 hr. For Cygnus X-3, there is no evidence for emission correlated with the 4.8 hr X-ray periodicity or with the occurrence of large radio flares. Unless one postulates that these sources were very active earlier and are now dormant, the limits presented here put into question the earlier results, and highlight the difficulties that possible future experiments will have in detecting gamma-ray signals at ultra-high energies.Comment: 26 LaTeX pages, 16 PostScript figures, uses psfig.sty to be published in Physical Review

Mitosis domain generalization in histopathology images -- The MIDOG challenge

The density of mitotic figures within tumor tissue is known to be highly correlated with tumor proliferation and thus is an important marker in tumor grading. Recognition of mitotic figures by pathologists is known to be subject to a strong inter-rater bias, which limits the prognostic value. State-of-the-art deep learning methods can support the expert in this assessment but are known to strongly deteriorate when applied in a different clinical environment than was used for training. One decisive component in the underlying domain shift has been identified as the variability caused by using different whole slide scanners. The goal of the MICCAI MIDOG 2021 challenge has been to propose and evaluate methods that counter this domain shift and derive scanner-agnostic mitosis detection algorithms. The challenge used a training set of 200 cases, split across four scanning systems. As a test set, an additional 100 cases split across four scanning systems, including two previously unseen scanners, were given. The best approaches performed on an expert level, with the winning algorithm yielding an F_1 score of 0.748 (CI95: 0.704-0.781). In this paper, we evaluate and compare the approaches that were submitted to the challenge and identify methodological factors contributing to better performance.Comment: 19 pages, 9 figures, summary paper of the 2021 MICCAI MIDOG challeng

Financing U.S. Graduate Medical Education: A Policy Position Paper of the Alliance for Academic Internal Medicine and the American College of Physicians

In this position paper, the Alliance for Academic Internal Medicine and the American College of Physicians examine the state of graduate medical education (GME) financing in the United States and recent proposals to reform GME funding. They make a series of recommendations to reform the current funding system to better align GME with the needs of the nation's health care workforce. These recommendations include using Medicare GME funds to meet policy goals and to ensure an adequate supply of physicians, a proper specialty mix, and appropriate training sites; spreading the costs of financing GME across the health care system; evaluating the true cost of training a resident and establishing a single per-resident amount; increasing transparency and innovation; and ensuring that primary care residents receive training in well-functioning ambulatory settings that are financially supported for their training roles

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

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