10-year Weight Change and Biological Aging in a Random Sample of 3,059 U.S. Adults

Telomeres play a key role in the protection of chromosomes. A good index of biological aging is the length of telomeres. Telomeres gradually shorten over time. Hence, they are strongly related to chronological age. Lifestyle is also an important factor influencing telomere length. PURPOSE: This investigation was designed to study the relationship between 10-yr weight change and leukocyte telomere length (LTL) in a large sample of 3,059 randomly selected U.S. adults, 35-70 years old. METHODS: NHANES (National Health and Nutrition Examination Survey) data were used with a cross-sectional design to determine the relationship between percent weight change and LTL. Percent weight change was calculated by subtracting baseline body weight 10-yrs earlier from current body weight and then dividing by the individual’s baseline body weight. The quantitative polymerase chain reaction method was used to measure LTL relative to standard reference DNA (T/S ratio). Covariates included age, sex, race/ethnicity, year of assessment, economic status, intent to lose weight, BMI, smoking, total physical activity, and disease status, (i.e., having or not having diabetes, cardiovascular disease, and/or cancer). Multiple regression was used to determine the linear relationship between percent weight change and LTL. Potential mediating variables were controlled using partial correlation. Because women and men differed significantly in percent 10-yr weight change and also telomere length, the data were analyzed separately by sex. RESULTS: After adjusting for age, race, year of assessment, and economic status, the association between percent 10-yr weight change and LTL was significant in women (F=8.0, P=0.0085). Controlling for all the covariates weakened the relationship slightly (F=6.5, P=0.0163). With all the covariates controlled, for each 1 percentage point increase in weight over the 10-yrs, telomeres were 3.96 base pairs (bp) shorter, on average. Given each 1-yr increase in age was associated with telomeres that were 14.2 bp shorter in women, each 3.6 percentage point increase in weight over the 10-yrs was predictive of 1 yr greater biological aging. 10-yr weight change was not associated with LTL in men. CONCLUSION: 10-yr weight change is a significant predictor of biological aging in U.S. women, but not in men

Abdominal Adiposity Indexed by the Sagittal Abdominal Diameter and Risk of Mortality in 14,119 U.S. Adults

The body mass index (BMI) is frequently used as a general measure of overweight and obesity. It is a good predictor of disease and premature death. However, research shows that indices of abdominal adiposity tend to be better predictors of disease risk and mortality than BMI. To date, the sagittal abdominal diameter (SAD), an index of abdominal adiposity, has never been evaluated as a predictor of mortality. PURPOSE: The present study was conducted to determine the extent that adults with different levels of SAD vary in their risk of all-cause mortality over an average follow-up of 6 years. METHODS: A total of 14,119 randomly selected adults, ages 20-79, from the National Health and Nutrition Examination Survey (NHANES), were included. SAD was measured by trained technicians during the years 2011-2016. The abdominal height of subjects was assessed in the supine position and a sliding-beam abdominal caliper with a built-in bubble was used to ensure a vertical measurement. Mortality data were acquired from the U.S. public-use linked mortality files (LMF), which are available for NHANES participants through 2018. Adjustments were made for 9 baseline potential confounding variables, including age, sex, race, BMI, cardiovascular disease, cancer, liver disease, smoking, and alcohol use. Subjects were divided into sex-specific quartiles based on their SAD values, and Cox proportional hazard ratios were calculated to determine risk of mortality over the follow-up period using SAS 9.4. RESULTS: With all the covariates controlled, hazard ratios showed a dose response relationship with all-cause mortality. Specifically, adults in Quartile 1 (Q1), those with the lowest sex-specific abdominal adiposity, had 0.45 (95% CI: 0.28-0.73) times the risk of mortality compared to those in Quartile 4 (Q4). Additionally, risk of mortality was 0.63 (95% CI: 0.42-0.95) for adults in Q2 vs Q4, and 0.67 (95% CI: 0.48-0.93) for Q3 vs Q4, each statistically significant. In the Q1 vs Q4 comparison, risk of mortality was 55% lower for those with the leanest SAD values. Overall, SAD was related to risk of all-cause mortality in a dose-response pattern. CONCLUSION: Epidemiologists and health care providers should seriously consider utilizing SAD as a screening tool within their programs. It is an excellent predictor of all-cause mortality

Ribosome Biogenesis Modulates Ty1 Copy Number Control in Saccharomyces cerevisiae.

Transposons can impact the host genome by altering gene expression and participating in chromosome rearrangements. Therefore, organisms evolved different ways to minimize the level of transposition. In Saccharomyces cerevisiae and its close relative S. paradoxus, Ty1 copy number control (CNC) is mediated by the self-encoded restriction factor p22, which is derived from the GAG capsid gene and inhibits virus-like particle (VLP) assembly and function. Based on secondary screens of Ty1 cofactors, we identified LOC1, a RNA localization/ribosome biogenesis gene that affects Ty1 mobility predominantly in strains harboring Ty1 elements. Ribosomal protein mutants rps0bΔ and rpl7aΔ displayed similar CNC-specific phenotypes as loc1Δ, suggesting that ribosome biogenesis is critical for CNC. The level of Ty1 mRNA and Ty1 internal (Ty1i) transcripts encoding p22 was altered in these mutants, and displayed a trend where the level of Ty1i RNA increased relative to full-length Ty1 mRNA. The level of p22 increased in these mutants, and the half-life of p22 also increased in a loc1Δ mutant. Transcriptomic analyses revealed small changes in the level of Ty1 transcripts or efficiency of translation initiation in a loc1Δ mutant. Importantly, a loc1Δ mutant had defects in assembly of Gag complexes and packaging Ty1 RNA. Our results indicate that defective ribosome biogenesis enhances CNC by increasing the level of p22, and raise the possibility for versatile links between VLP assembly, its cytoplasmic environment, and a novel stress response

Computational Topology and the Unique Games Conjecture

Covering spaces of graphs have long been useful for studying expanders (as "graph lifts") and unique games (as the "label-extended graph"). In this paper we advocate for the thesis that there is a much deeper relationship between computational topology and the Unique Games Conjecture. Our starting point is Linial\u27s 2005 observation that the only known problems whose inapproximability is equivalent to the Unique Games Conjecture - Unique Games and Max-2Lin - are instances of Maximum Section of a Covering Space on graphs. We then observe that the reduction between these two problems (Khot-Kindler-Mossel-O\u27Donnell, FOCS \u2704; SICOMP \u2707) gives a well-defined map of covering spaces. We further prove that inapproximability for Maximum Section of a Covering Space on (cell decompositions of) closed 2-manifolds is also equivalent to the Unique Games Conjecture. This gives the first new "Unique Games-complete" problem in over a decade. Our results partially settle an open question of Chen and Freedman (SODA, 2010; Disc. Comput. Geom., 2011) from computational topology, by showing that their question is almost equivalent to the Unique Games Conjecture. (The main difference is that they ask for inapproximability over Z_2, and we show Unique Games-completeness over Z_k for large k.) This equivalence comes from the fact that when the structure group G of the covering space is Abelian - or more generally for principal G-bundles - Maximum Section of a G-Covering Space is the same as the well-studied problem of 1-Homology Localization. Although our most technically demanding result is an application of Unique Games to computational topology, we hope that our observations on the topological nature of the Unique Games Conjecture will lead to applications of algebraic topology to the Unique Games Conjecture in the future

Concept-Guided Chain-of-Thought Prompting for Pairwise Comparison Scaling of Texts with Large Language Models

Existing text scaling methods often require a large corpus, struggle with short texts, or require labeled data. We develop a text scaling method that leverages the pattern recognition capabilities of generative large language models (LLMs). Specifically, we propose concept-guided chain-of-thought (CGCoT), which uses prompts designed to summarize ideas and identify target parties in texts to generate concept-specific breakdowns, in many ways similar to guidance for human coder content analysis. CGCoT effectively shifts pairwise text comparisons from a reasoning problem to a pattern recognition problem. We then pairwise compare concept-specific breakdowns using an LLM. We use the results of these pairwise comparisons to estimate a scale using the Bradley-Terry model. We use this approach to scale affective speech on Twitter. Our measures correlate more strongly with human judgments than alternative approaches like Wordfish. Besides a small set of pilot data to develop the CGCoT prompts, our measures require no additional labeled data and produce binary predictions comparable to a RoBERTa-Large model fine-tuned on thousands of human-labeled tweets. We demonstrate how combining substantive knowledge with LLMs can create state-of-the-art measures of abstract concepts.Comment: 26 pages, 2 figure

Dictionary-Assisted Supervised Contrastive Learning

Text analysis in the social sciences often involves using specialized dictionaries to reason with abstract concepts, such as perceptions about the economy or abuse on social media. These dictionaries allow researchers to impart domain knowledge and note subtle usages of words relating to a concept(s) of interest. We introduce the dictionary-assisted supervised contrastive learning (DASCL) objective, allowing researchers to leverage specialized dictionaries when fine-tuning pretrained language models. The text is first keyword simplified: a common, fixed token replaces any word in the corpus that appears in the dictionary(ies) relevant to the concept of interest. During fine-tuning, a supervised contrastive objective draws closer the embeddings of the original and keyword-simplified texts of the same class while pushing further apart the embeddings of different classes. The keyword-simplified texts of the same class are more textually similar than their original text counterparts, which additionally draws the embeddings of the same class closer together. Combining DASCL and cross-entropy improves classification performance metrics in few-shot learning settings and social science applications compared to using cross-entropy alone and alternative contrastive and data augmentation methods.Comment: 6 pages, 5 figures, EMNLP 202

The 8 o'clock Arc: A Serendipitous Discovery of a Strongly Lensed Lyman Break Galaxy in the SDSS DR4 Imaging Data

We report on the serendipitous discovery of the brightest Lyman Break Galaxy (LBG) currently known, a galaxy at z=2.73 that is being strongly lensed by the z=0.38 Luminous Red Galaxy (LRG) SDSS J002240.91+143110.4. The arc of this gravitational lens system, which we have dubbed the "8 o'clock arc" due to its time of discovery, was initially identified in the imaging data of the Sloan Digital Sky Survey Data Release 4 (SDSS DR4); followup observations on the Astrophysical Research Consortium (ARC) 3.5m telescope at Apache Point Observatory confirmed the lensing nature of this system and led to the identification of the arc's spectrum as that of an LBG. The arc has a spectrum and a redshift remarkably similar to those of the previous record-holder for brightest LBG (MS 1512-cB58, a.k.a "cB58"), but, with an estimated total magnitude of (g,r,i) = (20.0,19.2,19.0) and surface brightness of (mu_g,mu_r,mu_i) = (23.3, 22.5, 22.3) mag/arcsec^2, the 8 o'clock arc is thrice as bright. The 8 o'clock arc, which consists of three lensed images of the LBG, is 162deg (9.6arcsec) long and has a length-to-width ratio of 6:1. A fourth image of the LBG -- a counter-image -- can also be identified in the ARC 3.5m g-band images. A simple lens model for the system assuming a singular isothermal ellipsoid potential yields an Einstein radius of 2.91+/-0.14 arcsec, a total mass for the lensing LRG (within the (10.6+/-0.5)/h kpc enclosed by the lensed images) of 1.04x10^12/h Msun, and a magnification factor for the LBG of 12.3(+15/-3.6). The LBG itself is intrinsically quite luminous (approximately 6L*) and shows indications of massive recent star formation, perhaps as high as 160/h Msun/year.Comment: 4 pages 5 figures, submitted to ApJ Letter