New methods to measure residues coevolution in proteins

<p>Abstract</p> <p>Background</p> <p>The covariation of two sites in a protein is often used as the degree of their coevolution. To quantify the covariation many methods have been developed and most of them are based on residues position-specific frequencies by using the mutual information (MI) model.</p> <p>Results</p> <p>In the paper, we proposed several new measures to incorporate new biological constraints in quantifying the covariation. The first measure is the mutual information with the amino acid background distribution (MIB), which incorporates the amino acid background distribution into the marginal distribution of the MI model. The modification is made to remove the effect of amino acid evolutionary pressure in measuring covariation. The second measure is the mutual information of residues physicochemical properties (MIP), which is used to measure the covariation of physicochemical properties of two sites. The third measure called MIBP is proposed by applying residues physicochemical properties into the MIB model. Moreover, scores of our new measures are applied to a robust indicator <it>conn(k) </it>in finding the covariation signal of each site.</p> <p>Conclusions</p> <p>We find that incorporating amino acid background distribution is effective in removing the effect of evolutionary pressure of amino acids. Thus the MIB measure describes more biological background information for the coevolution of residues. Besides, our analysis also reveals that the covariation of physicochemical properties is a new aspect of coevolution information.</p

Scalable Multi-Robot Collaboration with Large Language Models: Centralized or Decentralized Systems?

A flurry of recent work has demonstrated that pre-trained large language models (LLMs) can be effective task planners for a variety of single-robot tasks. The planning performance of LLMs is significantly improved via prompting techniques, such as in-context learning or re-prompting with state feedback, placing new importance on the token budget for the context window. An under-explored but natural next direction is to investigate LLMs as multi-robot task planners. However, long-horizon, heterogeneous multi-robot planning introduces new challenges of coordination while also pushing up against the limits of context window length. It is therefore critical to find token-efficient LLM planning frameworks that are also able to reason about the complexities of multi-robot coordination. In this work, we compare the task success rate and token efficiency of four multi-agent communication frameworks (centralized, decentralized, and two hybrid) as applied to four coordination-dependent multi-agent 2D task scenarios for increasing numbers of agents. We find that a hybrid framework achieves better task success rates across all four tasks and scales better to more agents. We further demonstrate the hybrid frameworks in 3D simulations where the vision-to-text problem and dynamical errors are considered. See our project website https://yongchao98.github.io/MIT-REALM-Multi-Robot/ for prompts, videos, and code.Comment: 6 pages, 8 figure

Autotaxin upregulated by STAT3 activation contributes to invasion in pancreatic neuroendocrine neoplasms

Although the upregulation of autotaxin (ATX) is associated with many solid tumours, its role in pancreatic neuroendocrine neoplasms (pNEN) has not been well elucidated. The expression of ATX in pNEN tissues and pNEN cell line BON1 was analysed by Western blot, PCR and immunocytochemistry upon exposure to interleukin-6 (IL-6). Additionally, pNEN cell line BON1 was transfected with siRNAs against ATX or signal transducer and activator of transcription 3 (STAT3) and assessed by in vitro invasion assays. The following results were obtained. The expression of ATX in pNEN tissues was significantly increased compared with that in normal pancreatic tissues. High ATX expression was strongly correlated with tumour grade, lymph node metastasis and tumour-node-metastasis stage. Furthermore, ATX downregulation notably inhibited the metastatic capacity of pNEN cells, whereas STAT3 knockdown was found to downregulate the expression of ATX. ATX expression was upregulated in BON1 cells upon stimulation with IL-6, and this was accompanied by activation/phosphorylation of STAT3. Western blot analysis of human pNEN tissue extracts confirmed increased ATX expression and STAT3 phosphorylation with elevated expression levels of IL-6. In conclusion, ATX is upregulated in pNEN and is correlated with the metastatic capacity of pNEN cells, potentially via interaction with STAT3 activation