DoReMi: Grounding Language Model by Detecting and Recovering from Plan-Execution Misalignment

Large language models encode a vast amount of semantic knowledge and possess remarkable understanding and reasoning capabilities. Previous research has explored how to ground language models in robotic tasks to ensure that the sequences generated by the language model are both logically correct and practically executable. However, low-level execution may deviate from the high-level plan due to environmental perturbations or imperfect controller design. In this paper, we propose DoReMi, a novel language model grounding framework that enables immediate Detection and Recovery from Misalignments between plan and execution. Specifically, LLMs are leveraged for both planning and generating constraints for planned steps. These constraints can indicate plan-execution misalignments and we use a vision question answering (VQA) model to check constraints during low-level skill execution. If certain misalignment occurs, our method will call the language model to re-plan in order to recover from misalignments. Experiments on various complex tasks including robot arms and humanoid robots demonstrate that our method can lead to higher task success rates and shorter task completion times. Videos of DoReMi are available at https://sites.google.com/view/doremi-paper.Comment: 21 pages, 13 figure

Association of renin–angiotensin system inhibitors use with short- and long-term mortality in patients with aortic stenosis: A systematic review and meta-analysis

PurposeThe present study aimed to investigate the association of renin–angiotensin system inhibitors (RASi) with short- and long-term mortality in patients with aortic stenosis (AS).MethodsA systematic search was performed in PubMed, Embase, and Cochrane library databases for relevant studies published before March 2022. Studies meeting the inclusion criteria were included to assess the effect of RASi on short-term (≤30 days) and long-term (≥1 year) mortality in patients with AS.ResultsA total of 11 studies were included in the meta-analysis. Our results demonstrated that RASi reduced short-term mortality (OR = 0.76, 95% CI 0.63–0.93, p = 0.008) after aortic valve replacement (AVR). Subgroup analysis revealed that RASi was still associated with lower short-term mortality after transcatheter aortic valve replacement (TAVR); however, the association was relatively weak in patients who underwent surgical aortic valve replacement (SAVR). For long-term mortality, the pooled OR was 1.04 (95% CI 0.88–1.24, p = 0.63) after sensitivity analysis in patients who did not undergo AVR. In addition, our study confirmed that RASi significantly reduced long-term mortality (OR = 0.57, 95% CI 0.44–0.74, p < 0.0001) in patients who underwent AVR. Subgroup analysis showed that both TAVR and SAVR groups treated with RASi had lower long-term mortality.ConclusionRenin–angiotensin system inhibitors did not change long-term mortality in AS patients who did not undergo AVR. However, RASi reduced short- and long-term mortality in patients who underwent AVR

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

Customized Web Search Engine

The first search engine was found in 1990. Now Google is the largest search engine in the Internet. Search engines are used widely by internet users to search information. In this thesis I consider the features of search engines related to architecture, searching, and ranking. Also the history and categories of search engines is covered. I focus on the application of advanced search methods, like proximity searching, clustering searching, wild card searching, and stemming searching. I present a design for a ranking algorithm, which considers ranking comprehensively. I present the design and implementation of a new meta search engine CSEG which uses two major search engines, Google and Yahoo. The search results of CSEG and other search engines are compared and analyzed; the differences will be shown in detail

Nuclear Mass Predictions of the Relativistic Density Functional Theory with the Kernel Ridge Regression and the Application to <i>r</i>-Process Simulations

The kernel ridge regression (KRR) and its updated version taking into account the odd-even effects (KRRoe) are employed to improve the mass predictions of the relativistic density functional theory. Both the KRR and KRRoe approaches can improve the mass predictions to a large extent. In particular, the KRRoe approach can significantly improve the predictions of the one-nucleon separation energies. The extrapolation performances of the KRR and KRRoe approaches to neutron-rich nuclei are examined, and the impacts of the KRRoe mass corrections on the r-process simulations are studied. It is found that the KRRoe mass corrections for the nuclei in the r-process path are remarkable in the light mass region, e.g., A150, and this could influence the corresponding r-process abundances

Nuclear Mass Predictions of the Relativistic Density Functional Theory with the Kernel Ridge Regression and the Application to r-Process Simulations

The kernel ridge regression (KRR) and its updated version taking into account the odd-even effects (KRRoe) are employed to improve the mass predictions of the relativistic density functional theory. Both the KRR and KRRoe approaches can improve the mass predictions to a large extent. In particular, the KRRoe approach can significantly improve the predictions of the one-nucleon separation energies. The extrapolation performances of the KRR and KRRoe approaches to neutron-rich nuclei are examined, and the impacts of the KRRoe mass corrections on the r-process simulations are studied. It is found that the KRRoe mass corrections for the nuclei in the r-process path are remarkable in the light mass region, e.g., A&lt;150, and this could influence the corresponding r-process abundances

Longdan Xiegan Decoction alleviates experimental autoimmune uveitis in rats by inhibiting Notch signaling pathway activation and Th17 cell differentiation

This study aimed to investigate the dynamic effects of the traditional Chinese medicine compound Longdan Xiegan Decoction (LXD) on the inhibition of Notch signaling pathway activation and T helper (Th) cell differentiation in rats with experimental autoimmune uveitis (EAU). Based on a network pharmacology strategy, we conducted protein interaction network analysis to construct an active ingredient-disease treatment network. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were further used to screen out the possible signaling pathways regulated by LXD in the treatment of uveitis. In the subsequent functional studies, we established an EAU rat model and investigated the regulatory role of LXD in the Notch signaling pathway and Th cell differentiation in rats with EAU. Female Lewis rats were randomly divided into a normal control (NC) group, an EAU group, and an LXD group. After the induction of EAU, the ocular inflammation and pathological changes in the rats in each group were observed; for documentation, a scanning laser ophthalmoscope (SLO) was used to observe fundus inflammation on day 12 after immunization. Additionally, quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of Notch1, DLL4, IL-10 and IL-17A in the spleen, lymph nodes and ocular tissues of each group at 0, 6, 9, 12, 15 and 18 days after immunization. In addition, the dynamic frequencies of the CD4+, CD8+, Th17 and Treg cell subsets in the spleen, lymph nodes and ocular tissues were measured by flow cytometry. We found that the Notch signaling pathway was activated and the Th17 frequency was elevated in rats with EAU, leading to disrupted CD4+/CD8+ and Th17/Treg balance. The expression of Notch1, DLL4 and IL-17 mRNA and proteins in the EAU and LXD groups reached a peak on day 12, and then gradually decreased (all P < 0.05), and the ratios of the CD4+/CD8+ and Th17/Treg also peaked on day 12. However, after treatment with LXD, the expression of Notch1, DLL4 and IL-17 mRNA and proteins was significantly decreased (all P < 0.05), and the CD4+/CD8+ and Th17/Treg ratios significantly gradually returns to balance. LXD can efficiently inhibit Th17 cell differentiation, decrease inflammatory cytokine expression, and restore the CD4+/CD8+ and Th17/Treg balance by inhibiting the activation of the Notch signaling pathway in rats with EAU, thus effectively alleviating eye inflammation, protecting eye tissue structures, and positively regulating the immune state of the whole body and the intraocular microenvironment

Engineering of Saccharomyces pastorianus Old Yellow Enzyme 1 for the Synthesis of Pharmacologically Active (S)-Profen Derivatives

2-Arylpropionic acid derivatives, such as ibuprofen, constitute an important group of non-steroidal anti-inflammatory drugs (NSAIDs). Biocatalytic asymmetric reduction of 2-arylacrylic acid derivatives by ene reductases (EREDs) is a valuable approach for synthesis of these derivatives. However, previous bioreduction of 2-arylacrylic acid derivatives by either ERED wild-types or variants resulted solely in nonpharmacological (R)-enantiomers as the products. Here, we present the engineering of Saccharomyces pastorianus old yellow enzyme 1 (OYE1) into (S)-stereoselective enzymes, which afford pharmacologically active (S)-profen derivatives. By structural comparison of substrate recognition in related EREDs and analysis of non-covalent contacts in the pro-S model of OYE1, the key residues of OYE1 that switch its stereoselectivity to an (S)-stereopreference were identified. Systematic site-directed mutagenesis screening at these positions successfully provided the (S)-stereoselective OYE1 variants, which catalyzed stereoselective bioreduction of various profen precursors to afford pharmacologically active (S)-derivatives including (S)-ibuprofen and (S)-naproxen methyl esters with up to >99% ee values. Moreover, the key residues and mutation strategy obtained from OYE1 could be further transferred to OYE 2.6 (from Pichia stipitis) and KnOYE1 (from Kazachstania naganishii) to create the (S)-stereoselective EREDs. Our results may provide a generalizable strategy for stereocontrol of OYEs and set the basis for biocatalytic production of (S)-profens

PDGFRβ is an essential therapeutic target for BRCA1-deficient mammary tumors

Basal-like breast cancers (BLBCs) are a leading cause of cancer death due to their capacity to metastasize and lack of effective therapies. More than half of BLBCs have a dysfunctional BRCA1. Although most BRCA1-deficient cancers respond to DNA-damaging agents, resistance and tumor recurrence remain a challenge to survival outcomes for BLBC patients. Additional therapies targeting the pathways aberrantly activated by BRCA1 deficiency are urgently needed. Most BRCA1-deficient BLBCs carry a dysfunctional INK4-RB pathway. Thus, we created genetically engineered mice with Brca1 loss and deletion of p16 , or separately p18 , to model the deficient INK4-RB signaling in human BLBC. By using these mutant mice and human BRCA1-deficient and proficient breast cancer tissues and cells, we tested if there exists a druggable target in BRCA1-deficient breast cancers. Heterozygous germline or epithelium-specific deletion of Brca1 in p18 - or p16 -deficient mice activated Pdgfrβ signaling, induced epithelial-to-mesenchymal transition, and led to BLBCs. Confirming this role, targeted deletion of Pdgfrβ in Brca1-deficient tumor cells promoted cell death, induced mesenchymal-to-epithelial transition, and suppressed tumorigenesis. Importantly, we also found that pharmaceutical inhibition of Pdgfrβ and its downstream target Pkcα suppressed Brca1-deficient tumor initiation and progression and effectively killed BRCA1-deficient cancer cells. Our work offers the first genetic and biochemical evidence that PDGFRβ-PKCα signaling is repressed by BRCA1, which establishes PDGFRβ-PKCα signaling as a therapeutic target for BRCA1-deficient breast cancers