Transfer RNA genes experience exceptionally elevated mutation rates.

Transfer RNAs (tRNAs) are a central component for the biological synthesis of proteins, and they are among the most highly conserved and frequently transcribed genes in all living things. Despite their clear significance for fundamental cellular processes, the forces governing tRNA evolution are poorly understood. We present evidence that transcription-associated mutagenesis and strong purifying selection are key determinants of patterns of sequence variation within and surrounding tRNA genes in humans and diverse model organisms. Remarkably, the mutation rate at broadly expressed cytosolic tRNA loci is likely between 7 and 10 times greater than the nuclear genome average. Furthermore, evolutionary analyses provide strong evidence that tRNA genes, but not their flanking sequences, experience strong purifying selection acting against this elevated mutation rate. We also find a strong correlation between tRNA expression levels and the mutation rates in their immediate flanking regions, suggesting a simple method for estimating individual tRNA gene activity. Collectively, this study illuminates the extreme competing forces in tRNA gene evolution and indicates that mutations at tRNA loci contribute disproportionately to mutational load and have unexplored fitness consequences in human populations

Pharmacokinetic Analysis of a Phenobarbital Overdose Treated With Urinary Alkalinization Alone

Phenobarbital is a long-acting barbiturate used to treat alcohol withdrawal and epilepsy. Acute overdoses present with varying levels of central nervous system depression and large overdoses can be life threatening. Phenobarbital is an attractive candidate for enhanced elimination using urinary alkalinization given it is a weak acid with a long half-life and extensive urinary elimination. Limited human data exist regarding use of urine alkalinization for the treatment of phenobarbital overdose. We present a fourteen-year-old female who was treated with urinary alkalinization alone following an intentional ingestion of 3800 mg (84.4 mg/kg) of phenobarbital tablets. Urine drugs of abuse screening was preliminary positive for barbiturates and confirmed to be phenobarbital only. The initial serum phenobarbital concentration, drawn nine hours post-ingestion, was 97.4 mcg/ml (normal range 15-40 mcg/ml). Urinary alkalinization with sodium bicarbonate was started approximately 12 h post-ingestion and stopped at 72 h post-ingestion; clinical toxicity resolved by hospital day 5. The infusion was titrated to a urinary pH of greater than 7.5. Serial serum and urine phenobarbital measurements were obtained to determine elimination half-life and urinary excretion. The elimination half-life while undergoing urinary alkalinization was 81.3 h. Prior to initiation of urinary alkalinization, the urine phenobarbital concentration was 37 mcg/ml. Approximately 8.75 h after initiation, it was greater than 200 mcg/ml at a urine pH of 8.5. Urinary alkalinization appeared to augment urinary phenobarbital excretion, though with no discernible effect on elimination half-life and unclear clinical benefit. Further research is needed to better characterize the clinical effects of urinary alkalinization for phenobarbital overdose

Low work function material development for the microminiature thermionic converter.

Thermionic energy conversion in a miniature format shows potential as a viable, high efficiency, micro to macro-scale power source. A microminiature thermionic converter (MTC) with inter-electrode spacings on the order of microns has been prototyped and evaluated at Sandia. The remaining enabling technology is the development of low work function materials and processes that can be integrated into these converters to increase power production at modest temperatures (800 - 1300 K). The electrode materials are not well understood and the electrode thermionic properties are highly sensitive to manufacturing processes. Advanced theoretical, modeling, and fabrication capabilities are required to achieve optimum performance for MTC diodes. This report describes the modeling and fabrication efforts performed to develop micro dispenser cathodes for use in the MTC

The Vehicle, Spring 1994

Table of Contents Thoughts in the IGASue Songerpage 6 The Cries of an Innocent Tea BagWojnarowski Yvonnepage 7 Proud HarpySusan Eisenhourpage 8 Bus Number TwoMindy Glazepage 9 My Home TownScott Langenpage 10 MemoriesMaggie Willpage 11 Vase (Artwork)Gail Valkerpage 12 The Last HuntMark Kannmacherpage 13 Corn DanceJulia A. Canhampage 14 Untitled (Photography)Rachel Corbettpage 14 Paradise (Artwork)Gail Valkerpage 15 Holding Back A ScreamElise Kirarpage 16 poetry isJonathan W. Iwanskipage 17 loveCatherine DeGraafpage 18 The OneTim Rileypage 18 Reading His Words on a Frosty EveningTom McGrathpage 19 UntitledBob Newellpage 19 The Ice StormMindy Glazepage 20 UntitledJonathan W. Iwanskipage 21 Untitled (Photography)Rachel Corbettpage 23 cityscapeChris Pomeroypage 24 Untitled (Photography)Rachel Corbettpage 25 Quarter Pound TemptationBryan Levekpage 26 Photograph (Artwork)Gail Valkerpage 29 Don\u27t Talk to StrangersJon Montgomerypage 30 Untitled (Photography)Rachel Corbettpage 33 Charleston, U.S.A. (Artwork)Gail Valkerpage 34 Fun With Nature (Artwork)Gail Valkerpage 34https://thekeep.eiu.edu/vehicle/1064/thumbnail.jp

Total Daily Pill Burden in HIV-Infected Patients in the Southern United States

The need for antiretroviral therapy coupled with treatment of chronic co-morbidities places HIV-infected patients at risk for polypharmacy. However, few studies have described overall pill burden among HIV-infected patients. HIV-infected outpatients of the UNC Infectious Diseases Clinic were enrolled in this cross-sectional study. Subjects were contacted prior to a scheduled appointment and asked to bring all their medications to the visit. Daily total pill burden and medication type were recorded. 151 subjects were recruited: 76% male, 58% African American, 97% receiving antiretrovirals (ARVs). Median age was 48 (IRQ: 42–54) years. The median number of medications per subject was 8 (IQR: 6–11), and the median individual daily pill burden was 8 pills (IQR: 5–15): 3 pills (range: 2–5) for ARVs and 6 (range: 3–12.5) pills for non-ARVs. Duration of ART (per 2 years increase) and more than 3 co-morbidities was significantly associated with high pill burden (over 10 pills per day) with adjusted OR of 2.09 (95% CI, 1.14–3.84) and 8.04 (95% CI, 2.30–28.15), respectively. As patients with HIV age, strategies to reduce pill burden and number of medications will become increasingly critical to maintaining adherence, preventing medication errors, and serious drug–drug interactions

Stability of SARS-CoV-2 phylogenies.

Funder: Alfred P. Sloan Foundation; funder-id: http://dx.doi.org/10.13039/100000879Funder: European Molecular Biology Laboratory (EMBL)The SARS-CoV-2 pandemic has led to unprecedented, nearly real-time genetic tracing due to the rapid community sequencing response. Researchers immediately leveraged these data to infer the evolutionary relationships among viral samples and to study key biological questions, including whether host viral genome editing and recombination are features of SARS-CoV-2 evolution. This global sequencing effort is inherently decentralized and must rely on data collected by many labs using a wide variety of molecular and bioinformatic techniques. There is thus a strong possibility that systematic errors associated with lab-or protocol-specific practices affect some sequences in the repositories. We find that some recurrent mutations in reported SARS-CoV-2 genome sequences have been observed predominantly or exclusively by single labs, co-localize with commonly used primer binding sites and are more likely to affect the protein-coding sequences than other similarly recurrent mutations. We show that their inclusion can affect phylogenetic inference on scales relevant to local lineage tracing, and make it appear as though there has been an excess of recurrent mutation or recombination among viral lineages. We suggest how samples can be screened and problematic variants removed, and we plan to regularly inform the scientific community with our updated results as more SARS-CoV-2 genome sequences are shared (https://virological.org/t/issues-with-sars-cov-2-sequencing-data/473 and https://virological.org/t/masking-strategies-for-sars-cov-2-alignments/480). We also develop tools for comparing and visualizing differences among very large phylogenies and we show that consistent clade- and tree-based comparisons can be made between phylogenies produced by different groups. These will facilitate evolutionary inferences and comparisons among phylogenies produced for a wide array of purposes. Building on the SARS-CoV-2 Genome Browser at UCSC, we present a toolkit to compare, analyze and combine SARS-CoV-2 phylogenies, find and remove potential sequencing errors and establish a widely shared, stable clade structure for a more accurate scientific inference and discourse

Bringing People Back into Public Health Data: Community Feedback on a Set of Visualization Tools - Summary Report

This course-based study is a product of the University of Denver’s Spring 2022 The Social Determination of Health (ANTH 2424) class. The study aimed to understand how well a set of public health visualization tools tells the data stories about people in Colorado, and about important public health problems. For this, a team of almost sixty undergraduate students taking the class, coordinated by three graduate teaching assistants, and directed by the course instructor interviewed a total of fifty-six people from Colorado, qualitatively analyzed those interviews, and wrote reports that draw conclusions and recommendations