Geometrically Aligned Transfer Encoder for Inductive Transfer in Regression Tasks

Transfer learning is a crucial technique for handling a small amount of data that is potentially related to other abundant data. However, most of the existing methods are focused on classification tasks using images and language datasets. Therefore, in order to expand the transfer learning scheme to regression tasks, we propose a novel transfer technique based on differential geometry, namely the Geometrically Aligned Transfer Encoder (GATE). In this method, we interpret the latent vectors from the model to exist on a Riemannian curved manifold. We find a proper diffeomorphism between pairs of tasks to ensure that every arbitrary point maps to a locally flat coordinate in the overlapping region, allowing the transfer of knowledge from the source to the target data. This also serves as an effective regularizer for the model to behave in extrapolation regions. In this article, we demonstrate that GATE outperforms conventional methods and exhibits stable behavior in both the latent space and extrapolation regions for various molecular graph datasets.Comment: 12+11 pages, 6+1 figures, 0+7 table

Grouping-matrix based Graph Pooling with Adaptive Number of Clusters

Graph pooling is a crucial operation for encoding hierarchical structures within graphs. Most existing graph pooling approaches formulate the problem as a node clustering task which effectively captures the graph topology. Conventional methods ask users to specify an appropriate number of clusters as a hyperparameter, then assume that all input graphs share the same number of clusters. In inductive settings where the number of clusters can vary, however, the model should be able to represent this variation in its pooling layers in order to learn suitable clusters. Thus we propose GMPool, a novel differentiable graph pooling architecture that automatically determines the appropriate number of clusters based on the input data. The main intuition involves a grouping matrix defined as a quadratic form of the pooling operator, which induces use of binary classification probabilities of pairwise combinations of nodes. GMPool obtains the pooling operator by first computing the grouping matrix, then decomposing it. Extensive evaluations on molecular property prediction tasks demonstrate that our method outperforms conventional methods.Comment: 10 pages, 3 figure

3D Denoisers are Good 2D Teachers: Molecular Pretraining via Denoising and Cross-Modal Distillation

Pretraining molecular representations from large unlabeled data is essential for molecular property prediction due to the high cost of obtaining ground-truth labels. While there exist various 2D graph-based molecular pretraining approaches, these methods struggle to show statistically significant gains in predictive performance. Recent work have thus instead proposed 3D conformer-based pretraining under the task of denoising, which led to promising results. During downstream finetuning, however, models trained with 3D conformers require accurate atom-coordinates of previously unseen molecules, which are computationally expensive to acquire at scale. In light of this limitation, we propose D&D, a self-supervised molecular representation learning framework that pretrains a 2D graph encoder by distilling representations from a 3D denoiser. With denoising followed by cross-modal knowledge distillation, our approach enjoys use of knowledge obtained from denoising as well as painless application to downstream tasks with no access to accurate conformers. Experiments on real-world molecular property prediction datasets show that the graph encoder trained via D&D can infer 3D information based on the 2D graph and shows superior performance and label-efficiency against other baselines.Comment: 16 pages, 5 figure

Sensitivity to tumor development by TALEN-mediated Trp53 mutant genes in the susceptible FVB/N mice and the resistance C57BL/6 mice

Abstract Background This study was undertaken to compare the sensitivities of mice strains during tumor induction by transcription activator-like effector nucleases (TALEN)-mediated Trp53 mutant gene. Alterations of their tumorigenic phenotypes including survival rate, tumor formation and tumor spectrum, were assessed in FVB/N-Trp53em2Hwl/Korl and C57BL/6-Trp53em1Hwl/Korl knockout (KO) mice over 16weeks. Results Most of the physiological phenotypes factors were observed to be higher in FVB/N-Trp53em2Hwl/Korl KO mice than C57BL/6-Trp53em1Hwl/Korl KO mice, although there were significant differences in the body weight, immune organ weight, number of red blood cells, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count (PLT), total bilirubin (Bil-T) and glucose (Glu) levels in the KO mice relative to the wild type (WT) mice. Furthermore, numerous solid tumors were also observed in various regions of the surface skin of FVB/N-Trp53em2Hwl/Korl KO mice, but were not detected in C57BL/6-Trp53em1Hwl/Korl KO mice. The most frequently observed tumor in both the Trp53 KO mice was malignant lymphoma, while soft tissue teratomas and hemangiosarcomas were only detected in the FVB/N-Trp53em2Hwl/Korl KO mice. Conclusions Our results indicate that the spectrum and incidence of tumors induced by the TALEN-mediated Trp53 mutant gene is greater in FVB/N-Trp53em2Hwl/Korl KO mice than C57BL/6-Trp53em1Hwl/Korl KO mice over 16weeks

Second-Line Irinotecan, Leucovorin, and 5-Fluorouracil for Gastric Cancer Patients after Failed Docetaxel and S-1

Background. This retrospective study aimed to assess the efficacy and toxicities of second-line chemotherapy with irinotecan, leucovorin, and 5-fluorouracil (5-FU) in metastatic gastric cancer (MGC) patients previously treated with docetaxel and S-1 with or without oxaliplatin (DS/DOS). Patients and Methods. We reviewed the data of patients who had previously been treated with first-line DS/DOS and received biweekly irinotecan-based chemotherapy (FOLFIRI/IFL) between October 2004 and November 2011. Results. A total of 209 cycles were administered to 35 patients, with a median of 4 (range, 1–22) cycles each. The overall response rate in 29 response-assessable patients was 17.2%, including 2 complete and 3 partial responses. The median progression-free and overall survivals were 3.81 (95% confidence interval [CI], 1.82–5.80) months and 6.24 (95% CI, 1.44–11.04) months, respectively. The major grade 3/4 toxicity was neutropenia (8.6%). Conclusion. FOLFIRI/IFL chemotherapy showed modest antitumour activity and tolerable toxicities in DS/DOS-treated MGC patients

Second-Line Irinotecan, Leucovorin, and 5-Fluorouracil for Gastric Cancer Patients after Failed Docetaxel and S-1

Background. This retrospective study aimed to assess the efficacy and toxicities of second-line chemotherapy with irinotecan, leucovorin, and 5-fluorouracil (5-FU) in metastatic gastric cancer (MGC) patients previously treated with docetaxel and S-1 with or without oxaliplatin (DS/DOS). Patients and Methods. We reviewed the data of patients who had previously been treated with firstline DS/DOS and received biweekly irinotecan-based chemotherapy (FOLFIRI/IFL) between October 2004 and November 2011. Results. A total of 209 cycles were administered to 35 patients, with a median of 4 (range, 1-22) cycles each. The overall response rate in 29 response-assessable patients was 17.2%, including 2 complete and 3 partial responses. The median progression-free and overall survivals were 3.81 (95% confidence interval [CI], 1.82-5.80) months and 6.24 (95% CI, 1.44-11.04) months, respectively. The major grade 3/4 toxicity was neutropenia (8.6%). Conclusion. FOLFIRI/IFL chemotherapy showed modest antitumour activity and tolerable toxicities in DS/DOS-treated MGC patients

Estrogen receptor independent neurotoxic mechanism of bisphenol A, an environmental estrogen

Bisphenol A (BPA), a ubiquitous environmental contaminant, has been shown to cause developmental toxicity and carcinogenic effects. BPA may have physiological activity through estrogen receptor (ER) -α and -β, which are expressed in the central nervous system. We previously found that exposure of BPA to immature mice resulted in behavioral alternation, suggesting that overexposure of BPA could be neurotoxic. In this study, we further investigated the molecular neurotoxic mechanisms of BPA. BPA increased vulnerability (decrease of cell viability and differentiation, and increase of apoptotic cell death) of undifferentiated PC12 cells and cortical neuronal cells isolated from gestation 18 day rat embryos in a concentration-dependent manner (more than 50 µM). The ER antagonists, ICI 182,780, and tamoxifen, did not block these effects. The cell vulnerability against BPA was not significantly different in the PC12 cells overexpressing ER-α and ER-β compared with PC12 cells expressing vector alone. In addition, there was no difference observed between BPA and 17-β estradiol, a well-known agonist of ER receptor in the induction of neurotoxic responses. Further study of the mechanism showed that BPA significantly activated extracellular signal-regulated kinase (ERK) but inhibited anti-apoptotic nuclear factor kappa B (NF-κB) activation. In addition, ERK-specific inhibitor, PD 98,059, reversed BPA-induced cell death and restored NF-κB activity. This study demonstrated that exposure to BPA can cause neuronal cell death which may eventually be related with behavioral alternation in vivo. However, this neurotoxic effect may not be directly mediated through an ER receptor, as an ERK/NF-κB pathway may be more closely involved in BPA-induced neuronal toxicity