Evaluating the Ripple Effects of Knowledge Editing in Language Models

Modern language models capture a large body of factual knowledge. However, some facts can be incorrectly induced or become obsolete over time, resulting in factually incorrect generations. This has led to the development of various editing methods that allow updating facts encoded by the model. Evaluation of these methods has primarily focused on testing whether an individual fact has been successfully injected, and if similar predictions for other subjects have not changed. Here we argue that such evaluation is limited, since injecting one fact (e.g. ``Jack Depp is the son of Johnny Depp'') introduces a ``ripple effect'' in the form of additional facts that the model needs to update (e.g.``Jack Depp is the sibling of Lily-Rose Depp''). To address this issue, we propose a novel set of evaluation criteria that consider the implications of an edit on related facts. Using these criteria, we then construct \ripple{}, a diagnostic benchmark of 5K factual edits, capturing a variety of types of ripple effects. We evaluate prominent editing methods on \ripple{}, showing that current methods fail to introduce consistent changes in the model's knowledge. In addition, we find that a simple in-context editing baseline obtains the best scores on our benchmark, suggesting a promising research direction for model editing

Detecting cell-of-origin and cancer-specific methylation features of cell-free DNA from Nanopore sequencing

: The Oxford Nanopore (ONT) platform provides portable and rapid genome sequencing, and its ability to natively profile DNA methylation without complex sample processing is attractive for point-of-care real-time sequencing. We recently demonstrated ONT shallow whole-genome sequencing to detect copy number alterations (CNAs) from the circulating tumor DNA (ctDNA) of cancer patients. Here, we show that cell type and cancer-specific methylation changes can also be detected, as well as cancer-associated fragmentation signatures. This feasibility study suggests that ONT shallow WGS could be a powerful tool for liquid biopsy

First Results for Solar Soft X-ray Irradiance Measurements from the Third Generation Miniature X-Ray Solar Spectrometer

Three generations of the Miniature X-ray Solar Spectrometer (MinXSS) have flown on small satellites with the goal "to explore the energy distribution of soft X-ray (SXR) emissions from the quiescent Sun, active regions, and during solar flares, and to model the impact on Earth's ionosphere and thermosphere". The primary science instrument is the Amptek X123 X-ray spectrometer that has improved with each generation of the MinXSS experiment. This third generation MinXSS-3 has higher energy resolution and larger effective area than its predecessors and is also known as the Dual-zone Aperture X-ray Solar Spectrometer (DAXSS). It was launched on the INSPIRESat-1 satellite on 2022 February 14, and INSPIRESat-1 has successfully completed its 6-month prime mission. The INSPIRESat-1 is in a dawn-dusk, Sun-Synchronous Orbit (SSO) and therefore has 24-hour coverage of the Sun during most of its mission so far. The rise of Solar Cycle 25 (SC-25) has been observed by DAXSS. This paper introduces the INSPIRESat-1 DAXSS solar SXR observations, and we focus the science results here on a solar occultation experiment and multiple flares on 2022 April 24. One key flare result is that the reduction of elemental abundances is greatest during the flare impulsive phase and thus highlighting the important role of chromospheric evaporation during flares to inject warmer plasma into the coronal loops. Furthermore, these results are suggestive that the amount of chromospheric evaporation is related to flare temperature and intensity.Comment: 43 pages including 19-page Appendix A, 8 figures, 7 table

In sickness and in health: the role of methyl-CpG binding protein 2 in the central nervous system

The array of specialized neuronal and glial cell types that characterize the adult central nervous system originates from neuroepithelial proliferating precursor cells. The transition from proliferating neuroepithelial precursor cells to neuronal lineages is accompanied by rapid global changes in gene expression in coordination with epigenetic modifications at the level of the chromatin structure. A number of genetic studies have begun to reveal how epigenetic deregulation results in neurodevelopmental disorders such as mental retardation, autism, Rubinstein–Taybi syndrome and Rett syndrome. In this review we focus on the role of the methyl-CpG binding protein 2 (MeCP2) during development of the central nervous system and its involvement in Rett syndrome. First, we present recent findings that indicate a previously unconsidered role of glial cells in the development of Rett syndrome. Next, we discuss evidence of how MeCP2 deficiency or loss of function results in aberrant gene expression leading to Rett syndrome. We also discuss MeCP2's function as a repressor and activator of gene expression and the role of its different target genes, including microRNAs, during neuronal development. Finally, we address different signaling pathways that regulate MeCP2 expression at both the post-transcriptional and post-translational level, and discuss how mutations in MeCP2 may result in lack of responsiveness to environmental signals

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data