1,626 research outputs found
Recommended from our members
Force-induced recruitment of cten along keratin network in epithelial cells.
The cytoskeleton provides structural integrity to cells and serves as a key component in mechanotransduction. Tensins are thought to provide a force-bearing linkage between integrins and the actin cytoskeleton; yet, direct evidence of tensin's role in mechanotransduction is lacking. We here report that local force application to epithelial cells using a micrometer-sized needle leads to rapid accumulation of cten (tensin 4), but not tensin 1, along a fibrous intracellular network. Surprisingly, cten-positive fibers are not actin fibers; instead, these fibers are keratin intermediate filaments. The dissociation of cten from tension-free keratin fibers depends on the duration of cell stretch, demonstrating that the external force favors maturation of cten-keratin network interactions over time and that keratin fibers retain remarkable structural memory of a cell's force-bearing state. These results establish the keratin network as an integral part of force-sensing elements recruiting distinct proteins like cten and suggest the existence of a mechanotransduction pathway via keratin network
BooookScore: A systematic exploration of book-length summarization in the era of LLMs
Summarizing book-length documents (>100K tokens) that exceed the context
window size of large language models (LLMs) requires first breaking the input
document into smaller chunks and then prompting an LLM to merge, update, and
compress chunk-level summaries. Despite the complexity and importance of this
task, it has yet to be meaningfully studied due to the challenges of
evaluation: existing book-length summarization datasets (e.g., BookSum) are in
the pretraining data of most public LLMs, and existing evaluation methods
struggle to capture errors made by modern LLM summarizers. In this paper, we
present the first study of the coherence of LLM-based book-length summarizers
implemented via two prompting workflows: (1) hierarchically merging chunk-level
summaries, and (2) incrementally updating a running summary. We obtain 1193
fine-grained human annotations on GPT-4 generated summaries of 100
recently-published books and identify eight common types of coherence errors
made by LLMs. Because human evaluation is expensive and time-consuming, we
develop an automatic metric, BooookScore, that measures the proportion of
sentences in a summary that do not contain any of the identified error types.
BooookScore has high agreement with human annotations and allows us to
systematically evaluate the impact of many other critical parameters (e.g.,
chunk size, base LLM) while saving $15K and 500 hours in human evaluation
costs. We find that closed-source LLMs such as GPT-4 and Claude 2 produce
summaries with higher BooookScore than the oft-repetitive ones generated by
LLaMA 2. Incremental updating yields lower BooookScore but higher level of
detail than hierarchical merging, a trade-off sometimes preferred by human
annotators. We release code and annotations after blind review to spur more
principled research on book-length summarization
Recommended from our members
Chromatin Modification by PSC Occurs at One PSC per Nucleosome and Does Not Require the Acidic Patch of Histone H2A
Chromatin architecture is regulated through both enzymatic and non-enzymatic activities. For example, the Polycomb Group (PcG) proteins maintain developmental gene silencing using an array of chromatin-based mechanisms. The essential Drosophila PcG protein, Posterior Sex Combs (PSC), compacts chromatin and inhibits chromatin remodeling and transcription through a non-enzymatic mechanism involving nucleosome bridging. Nucleosome bridging is achieved through a combination of nucleosome binding and self-interaction. Precisely how PSC interacts with chromatin to bridge nucleosomes is not known and is the subject of this work. We determine the stoichiometry of PSC-chromatin interactions in compact chromatin (in which nucleosomes are bridged) using Scanning Transmission Electron Microscopy (STEM). We find that full compaction occurs with one PSC per nucleosome. In addition to compacting chromatin, we show that PSC oligomerizes nucleosome arrays. PSC-mediated oligomerization of chromatin occurs at similar stoichiometry as compaction suggesting it may also involve nucleosome bridging. Interactions between the tail of histone H4 and the acidic patch of histone H2A are important for chromatin folding and oligomerization, and several chromatin proteins bind the histone H2A acidic patch. However, mutation of the acidic patch of histone H2A does not affect PSC’s ability to inhibit chromatin remodeling or bridge nucleosomes. In fact, PSC does not require nucleosomes for bridging activity but can bridge naked DNA segments. PSC clusters nucleosomes on sparsely assembled templates, suggesting it interacts preferentially with nucleosomes over bare DNA. This may be due to the ability of PSC to bind free histones. Our data are consistent with a model in which each PSC binds a nucleosome and at least one other PSC to directly bridge nucleosomes and compact chromatin, but also suggest that naked DNA can be included in compacted structures. We discuss how our data highlight the diversity of mechanisms used to modify chromatin architecture.Molecular and Cellular Biolog
Decomposing Complex Queries for Tip-of-the-tongue Retrieval
When re-finding items, users who forget or are uncertain about identifying
details often rely on creative strategies for expressing their information
needs -- complex queries that describe content elements (e.g., book characters
or events), information beyond the document text (e.g., descriptions of book
covers), or personal context (e.g., when they read a book). This retrieval
setting, called tip of the tongue (TOT), is especially challenging for models
heavily reliant on lexical and semantic overlap between query and document
text. In this work, we introduce a simple yet effective framework for handling
such complex queries by decomposing the query into individual clues, routing
those as sub-queries to specialized retrievers, and ensembling the results.
This approach allows us to take advantage of off-the-shelf retrievers (e.g.,
CLIP for retrieving images of book covers) or incorporate retriever-specific
logic (e.g., date constraints). We show that our framework incorportating query
decompositions into retrievers can improve gold book recall up to 7% relative
again for Recall@5 on a new collection of 14,441 real-world query-book pairs
from an online community for resolving TOT inquiries
LIMEADE: A General Framework for Explanation-Based Human Tuning of Opaque Machine Learners
Research in human-centered AI has shown the benefits of systems that can
explain their predictions. Methods that allow humans to tune a model in
response to the explanations are similarly useful. While both capabilities are
well-developed for transparent learning models (e.g., linear models and GA2Ms),
and recent techniques (e.g., LIME and SHAP) can generate explanations for
opaque models, no method for tuning opaque models in response to explanations
has been user-tested to date. This paper introduces LIMEADE, a general
framework for tuning an arbitrary machine learning model based on an
explanation of the model's prediction. We demonstrate the generality of our
approach with two case studies. First, we successfully utilize LIMEADE for the
human tuning of opaque image classifiers. Second, we apply our framework to a
neural recommender system for scientific papers on a public website and report
on a user study showing that our framework leads to significantly higher
perceived user control, trust, and satisfaction. Analyzing 300 user logs from
our publicly-deployed website, we uncover a tradeoff between canonical greedy
explanations and diverse explanations that better facilitate human tuning.Comment: 16 pages, 7 figure
- …