Unlock the Potential of Counterfactually-Augmented Data in Out-Of-Distribution Generalization

Counterfactually-Augmented Data (CAD) -- minimal editing of sentences to flip the corresponding labels -- has the potential to improve the Out-Of-Distribution (OOD) generalization capability of language models, as CAD induces language models to exploit domain-independent causal features and exclude spurious correlations. However, the empirical results of CAD's OOD generalization are not as efficient as anticipated. In this study, we attribute the inefficiency to the myopia phenomenon caused by CAD: language models only focus on causal features that are edited in the augmentation operation and exclude other non-edited causal features. Therefore, the potential of CAD is not fully exploited. To address this issue, we analyze the myopia phenomenon in feature space from the perspective of Fisher's Linear Discriminant, then we introduce two additional constraints based on CAD's structural properties (dataset-level and sentence-level) to help language models extract more complete causal features in CAD, thereby mitigating the myopia phenomenon and improving OOD generalization capability. We evaluate our method on two tasks: Sentiment Analysis and Natural Language Inference, and the experimental results demonstrate that our method could unlock the potential of CAD and improve the OOD generalization performance of language models by 1.0% to 5.9%.Comment: Expert Systems With Applications 2023. arXiv admin note: text overlap with arXiv:2302.0934

Missing call bias in high-throughput genotyping

© 2009 Fu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Oceanic response to typhoons in the Northwest Pacific using Aquarius and SMAP data (2011–2020)

Typhoons, such as tropical cyclones, can produce a variety of ocean responses through drastic changes in atmospheric and oceanic environments. However, the uncertainty in satellite salinity data increases during the passage of a typhoon and may limit its potential application. To investigate whether the satellite salinity data can explain oceanic responses to typhoons in the Northwest Pacific, we validated the satellite salinity using Argo float data for the past decade (2011–2020). The Soil Moisture Active Passive (SMAP) and Aquarius salinity were relatively accurate in subtropical regions at low latitudes under high sea surface temperature conditions in summer. This demonstrates the validity of the satellite salinity data in typhoon studies. We analyzed the oceanic responses to 20 representative typhoons over the past decade. Both the Aquarius and SMAP satellites observed a decrease in the SSS on the left side of the typhoon in contrast to the high salinity on the right side of the typhoon. The locations of SSS freshening coincided with those of higher precipitation to the left of the typhoon centers. We also observed that the higher the precipitation rate, the lower the satellite salinity. The ratio of the salinity freshening to the precipitation rate was significant at approximately –0.0401 psu mm-1 h-1. Changes in the vertical profiles of the Argo data supported this partial freshening of salinity as well as the characteristic surface cooling and deepening of the mixed layer after the passage of the typhoon. We further demonstrated that the atmospheric environments in a rotated coordinate system along the typhoon paths showed clear salinity freshening in the forward and slightly left sides of the typhoon center. The spatial distinction of the wind and precipitation fields along the typhoon paths induced the characteristic synoptic response of salinity prior to the arrival of each typhoon. Our results provide reasonable observational evidence of oceanic responses to typhoons in the Northwest Pacific and contribute to the understanding of atmospheric and oceanic processes related to tropical storms

The effect of hamstring donor-site block for functional outcomes and rehabilitation after anterior cruciate ligament reconstruction

PurposeTo determine the effect of local infiltration anesthesia (LIA) at the donor site combined with a femoral nerve block (FNB) on short-term postoperative pain, functional outcomes, and rehabilitation after arthroscopic hamstring tendon autograft anterior cruciate ligament reconstruction (ACLR).MethodsThis study was a single center, randomized controlled trial. Seventy-three subjects with ACL rupture were enrolled. Participants were randomly allocated to two groups, 47 in the experimental group (Group A) and 26 in the control group (Group B). All operations were performed under FNB. In Group A, 10 ml of 1% ropivacaine was injected precisely at the hamstring donor site. Patients in Group B were treated with the same amount of saline. Preoperatively and postoperatively, pain scores based on the numerical rating scale (NRS) and consumption of opioids were recorded. In addition, knee functions were assessed by the International Knee Documentation Committee Subjective Knee Form (IKDC), the Lysholm score, and the Knee injury and Osteoarthritis Outcome Score (KOOS) preoperatively and postoperatively at 1 and 3 months. In addition, we applied the KNEELAX3 arthrometer to evaluate the stability of the knee preoperatively and postoperatively so that subjective and objective knee conditions were obtained to help us assess knee recovery in a comprehensive manner.ResultsThe hamstring donor-site block reduced pain within the first 12 postoperative hours. There were no significant differences between two groups in pain intensity preoperatively and equal to or greater than 24 hours postoperatively. Furthermore, there were no differences between the groups concerning knee functions preoperatively or in the short-term follow-up at 1 and 3 months.ConclusionLIA at the donor site can effectively improve the early postoperative pain of patients after ACLR and reduce the use of opioids without affecting the functional outcomes of the surgery

Structure-Based Rational Design of a Toll-like Receptor 4 (TLR4) Decoy Receptor with High Binding Affinity for a Target Protein

Repeat proteins are increasingly attracting much attention as alternative scaffolds to immunoglobulin antibodies due to their unique structural features. Nonetheless, engineering interaction interface and understanding molecular basis for affinity maturation of repeat proteins still remain a challenge. Here, we present a structure-based rational design of a repeat protein with high binding affinity for a target protein. As a model repeat protein, a Toll-like receptor4 (TLR4) decoy receptor composed of leucine-rich repeat (LRR) modules was used, and its interaction interface was rationally engineered to increase the binding affinity for myeloid differentiation protein 2 (MD2). Based on the complex crystal structure of the decoy receptor with MD2, we first designed single amino acid substitutions in the decoy receptor, and obtained three variants showing a binding affinity (KD) one-order of magnitude higher than the wild-type decoy receptor. The interacting modes and contributions of individual residues were elucidated by analyzing the crystal structures of the single variants. To further increase the binding affinity, single positive mutations were combined, and two double mutants were shown to have about 3000- and 565-fold higher binding affinities than the wild-type decoy receptor. Molecular dynamics simulations and energetic analysis indicate that an additive effect by two mutations occurring at nearby modules was the major contributor to the remarkable increase in the binding affinities

Direct Inhibition of GSK3β by the Phosphorylated Cytoplasmic Domain of LRP6 in Wnt/β-Catenin Signaling

Wnt/β-catenin signaling plays a central role in development and is also involved in a diverse array of diseases. Binding of Wnts to the coreceptors Frizzled and LRP6/5 leads to phosphorylation of PPPSPxS motifs in the LRP6/5 intracellular region and the inhibition of GSK3β bound to the scaffold protein Axin. However, it remains unknown how GSK3β is specifically inhibited upon Wnt stimulation. Here, we show that overexpression of the intracellular region of LRP6 containing a Ser/Thr rich cluster and a PPPSPxS motif impairs the activity of GSK3β in cells. Synthetic peptides containing the PPPSPxS motif strongly inhibit GSK3β in vitro only when they are phosphorylated. Microinjection of these peptides into Xenopus embryos confirms that the phosphorylated PPPSPxS motif potentiates Wnt-induced second body axis formation. In addition, we show that the Ser/Thr rich cluster of LRP6 plays an important role in LRP6 binding to GSK3β. These observations demonstrate that phosphorylated LRP6/5 both recruits and directly inhibits GSK3β using two distinct portions of its cytoplasmic sequence, and suggest a novel mechanism of activation in this signaling pathway