A New Benchmark and Reverse Validation Method for Passage-level Hallucination Detection

Large Language Models (LLMs) have shown their ability to collaborate effectively with humans in real-world scenarios. However, LLMs are apt to generate hallucinations, i.e., makeup incorrect text and unverified information, which can cause significant damage when deployed for mission-critical tasks. In this paper, we propose a self-check approach based on reverse validation to detect factual errors automatically in a zero-resource fashion. To facilitate future studies and assess different methods, we construct a hallucination detection benchmark named PHD, which is generated by ChatGPT and annotated by human annotators. Contrasting previous studies of zero-resource hallucination detection, our method and benchmark concentrate on passage-level detection instead of sentence-level. We empirically evaluate our method and existing zero-resource detection methods on two datasets. The experimental results demonstrate that the proposed method considerably outperforms the baselines while costing fewer tokens and less time. Furthermore, we manually analyze some hallucination cases that LLM failed to capture, revealing the shared limitation of zero-resource methods.Comment: EMNLP2023 Finding

Exploiting Summarization Data to Help Text Simplification

One of the major problems with text simplification is the lack of high-quality data. The sources of simplification datasets are limited to Wikipedia and Newsela, restricting further development of this field. In this paper, we analyzed the similarity between text summarization and text simplification and exploited summarization data to help simplify. First, we proposed an alignment algorithm to extract sentence pairs from summarization datasets. Then, we designed four attributes to characterize the degree of simplification and proposed a method to filter suitable pairs. We named these pairs Sum4Simp (S4S). Next, we conducted human evaluations to show that S4S is high-quality and compared it with a real simplification dataset. Finally, we conducted experiments to illustrate that the S4S can improve the performance of several mainstream simplification models, especially in low-resource scenarios.Comment: 13 pages, 4 figures, EACL 202

ISWI Remodelling of Physiological Chromatin Fibres Acetylated at Lysine 16 of Histone H4

ISWI is the catalytic subunit of several ATP-dependent chromatin remodelling factors that catalyse the sliding of nucleosomes along DNA and thereby endow chromatin with structural flexibility. Full activity of ISWI requires residues of a basic patch of amino acids in the N-terminal 'tail' of histone H4. Previous studies employing oligopeptides and mononucleosomes suggested that acetylation of the H4 tail at lysine 16 (H4K16) within the basic patch may inhibit the activity of ISWI. On the other hand, the acetylation of H4K16 is known to decompact chromatin fibres. Conceivably, decompaction may enhance the accessibility of nucleosomal DNA and the H4 tail for ISWI interactions. Such an effect can only be evaluated at the level of nucleosome arrays. We probed the influence of H4K16 acetylation on the ATPase and nucleosome sliding activity of Drosophila ISWI in the context of defined, in vitro reconstituted chromatin fibres with physiological nucleosome spacing and linker histone content. Contrary to widespread expectations, the acetylation did not inhibit ISWI activity, but rather stimulated ISWI remodelling under certain conditions. Therefore, the effect of H4K16 acetylation on ISWI remodelling depends on the precise nature of the substrate

Combination Therapy Strategy of Quorum Quenching Enzyme and Quorum Sensing Inhibitor in Suppressing Multiple Quorum Sensing Pathways of P. <i>aeruginosa</i>

Abstract The threat of antibiotic resistant bacteria has called for alternative antimicrobial strategies that would mitigate the increase of classical resistance mechanism. Many bacteria employ quorum sensing (QS) to govern the production of virulence factors and formation of drug-resistant biofilms. Targeting the mechanism of QS has proven to be a functional alternative to conventional antibiotic control of infections. However, the presence of multiple QS systems in individual bacterial species poses a challenge to this approach. Quorum sensing inhibitors (QSI) and quorum quenching enzymes (QQE) have been both investigated for their QS interfering capabilities. Here, we first simulated the combination effect of QQE and QSI in blocking bacterial QS. The effect was next validated by experiments using AiiA as QQE and G1 as QSI on Pseudomonas aeruginosa LasR/I and RhlR/I QS circuits. Combination of QQE and QSI almost completely blocked the P. aeruginosa las and rhl QS systems. Our findings provide a potential chemical biology application strategy for bacterial QS disruption

The effect of socioeconomic status on three-year mortality after first-ever ischemic stroke in Nanjing, China

BACKGROUND: Low socioeconomic status (SES) is associated with increased mortality after stroke in developed countries. This study was performed to determine whether a similar association also exists in China. METHODS: A total of 806 patients with first-ever ischemic stroke were enrolled in our study. From August 1999 to August 2005, the three-year all-cause mortality following the stroke was determined. Level of education, occupation, taxable income and housing space were used as indicators for SES. Stepwise univariate and multivariate COX proportional hazards models were used to study the association between the SES measures and the three-year mortality. RESULTS: Our analyses confirmed that occupation, taxable income and housing space were significantly associated with three-year mortality after first-ever stroke. Manual workers had a significant hazard ratio of 5.44 (95% CI 2.75 to 10.77) for death within three years when compared with non-manual workers. Those in the zero income group had a significant hazard ratio of 5.35 (95% CI 2.95 to 9.70) and those in the intermediate income group 2.10 (95% CI 1.24 to 3.58) when compared with those in the highest income group. Those in two of the three groups with the smallest housing space also had significant hazard ratios of 2.06 (95% CI 1.16 to 3.65) and 1.68 (95% CI 1.12 to 2.52) when compared with those in group with the largest housing space. These hazard ratios remained largely unchanged after multivariate adjustment for age, gender, baseline cardiovascular disease risk factors, and stroke severity. The analyses did not confirm an association with educational level. CONCLUSION: Lower SES has a negative impact on the outcome of first-ever stroke in Nanjing, China. This confirms the need to improve preventive and secondary care for stroke among low SES groups

The effects of histone H4 tail acetylations on cation-induced chromatin folding and self-association

Understanding the molecular mechanisms behind regulation of chromatin folding through covalent modifications of the histone N-terminal tails is hampered by a lack of accessible chromatin containing precisely modified histones. We study the internal folding and intermolecular self-association of a chromatin system consisting of saturated 12-mer nucleosome arrays containing various combinations of completely acetylated lysines at positions 5, 8, 12 and 16 of histone H4, induced by the cations Na+, K+, Mg2+, Ca2+, cobalt-hexammine3+, spermidine3+ and spermine4+. Histones were prepared using a novel semi-synthetic approach with native chemical ligation. Acetylation of H4-K16, but not its glutamine mutation, drastically reduces cation-induced folding of the array. Neither acetylations nor mutations of all the sites K5, K8 and K12 can induce a similar degree of array unfolding. The ubiquitous K+, (as well as Rb+ and Cs+) showed an unfolding effect on unmodified arrays almost similar to that of H4-K16 acetylation. We propose that K+ (and Rb+/Cs+) binding to a site on the H2B histone (R96-L99) disrupts H4K16 ε-amino group binding to this specific site, thereby deranging H4 tail-mediated nucleosome–nucleosome stacking and that a similar mechanism operates in the case of H4-K16 acetylation. Inter-array self-association follows electrostatic behavior and is largely insensitive to the position or nature of the H4 tail charge modification

Development of novel chemical ligation methods for the synthesis of posttranslationally modified proteins

Proteins are the central molecules of life. They play important functional roles in vitually every biological process. Peptide and protein chemical synthesis is an enabling tool for the study of the structure and function of proteins, especially those with posttranslational modifications (PTMs), which are difficult to access by the traditional recombinant techniques. Since the development of solid-phase peptide synthesis (SPPS) and many chemical ligation methods, such as thioester-mediated native chemical ligation, the chemical synthesis of peptides and proteins are revolutionized. Proteins with PTMs remain challenging for biochemists to synthesize utilizing currently available approaches. During my Ph.D study, my work focused on the development of novel chemical methods to overcome these challenges. In this thesis, I am going to present some of my achievements in methodology development for the synthesis of some typical protein PTMs. In chapter 1, a brief introduction to the background of PTMs, the development of modern peptide chemistry and the methods for the preparation of proteins with PTMs were given. In chapter 2, we present the ligation/S-alkylation approach which we successfully applied to the synthesis N-terminal tail acetylated histone H4. Three different H4 variants with combinations of acetylation(s) at lysine 5, 8, 12 and 16 were synthesized using the ligation/S-alkylation approach. In chapter 3 and 4, we focus on the development of methods for the site-specific chemical ubiquitination of peptides and proteins. In chapter 3, we introduce a novel chemical ligation method named dual native chemical ligation at lysine. The dual ligation refers to the ligation at both α- and ε-amine of lysine mediated by the thiol group of 4-thiolysine. This dual ligation approach does not only expand the scope of chemical ligation to lysine residue but also provides an efficient chemical approach for site-specific ubiquitination. In chapter 4, we modify and improve our dual chemical ligation approach and apply it in the synthesis of a K48-linked diubiquitin. This demonstrated the feasibility of our methodology in synthesizing ubiquitinated proteins. In chapter 5, we developed a novel N- to C-terminus sequential chemical ligation approach for protein synthesis. This approach works through the combination of native chemical ligation and peptidyl N,N-bis(2-mercaptoethyl)-amide (BMEA) mediated ligation. We first demonstrated the feasibility of the approach using small model peptides and then applied the approach to the chemical synthesis of ubiquitin. In the concluding chapter, I review and discuss the current achievements in chemical synthesis of acetylated and ubiquitinated proteins since these two PTMs are important but challenging to be accessed by chemical approaches.DOCTOR OF PHILOSOPHY (SBS