42 research outputs found
SG-Net: Syntax-Guided Machine Reading Comprehension
For machine reading comprehension, the capacity of effectively modeling the
linguistic knowledge from the detail-riddled and lengthy passages and getting
ride of the noises is essential to improve its performance. Traditional
attentive models attend to all words without explicit constraint, which results
in inaccurate concentration on some dispensable words. In this work, we propose
using syntax to guide the text modeling by incorporating explicit syntactic
constraints into attention mechanism for better linguistically motivated word
representations. In detail, for self-attention network (SAN) sponsored
Transformer-based encoder, we introduce syntactic dependency of interest (SDOI)
design into the SAN to form an SDOI-SAN with syntax-guided self-attention.
Syntax-guided network (SG-Net) is then composed of this extra SDOI-SAN and the
SAN from the original Transformer encoder through a dual contextual
architecture for better linguistics inspired representation. To verify its
effectiveness, the proposed SG-Net is applied to typical pre-trained language
model BERT which is right based on a Transformer encoder. Extensive experiments
on popular benchmarks including SQuAD 2.0 and RACE show that the proposed
SG-Net design helps achieve substantial performance improvement over strong
baselines.Comment: Thirty-Fourth AAAI Conference on Artificial Intelligence (AAAI-2020
An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease
There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. Targeting drugs selectively to the inflamed intestine may improve therapeutic outcomes and minimize systemic toxicity. We report the development of an inflammation-targeting hydrogel (IT-hydrogel) that acts as a drug delivery system to the inflamed colon. Hydrogel microfibers were generated from ascorbyl palmitate, an amphiphile that is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration. IT-hydrogel microfibers loaded with the anti-inflammatory corticosteroid dexamethasone (Dex) were stable, released drug only upon enzymatic digestion, and demonstrated preferential adhesion to inflamed epithelial surfaces in vitro and in two mouse colitis models in vivo. Dex-loaded IT-hydrogel enemas, but not free Dex enemas, administered every other day to mice with colitis resulted in a significant reduction in inflammation and were associated with lower Dex peak serum concentrations and, thus, less systemic drug exposure. Ex vivo analysis of colon tissue samples from patients with ulcerative colitis demonstrated that IT-hydrogel microfibers adhered preferentially to mucosa from inflamed lesions compared with histologically normal sites. The IT-hydrogel drug delivery platform represents a promising approach for targeted enema-based therapies in patients with colonic IBD
Response to the Letter to the Editor by D. Richardson: Analysis of the Interaction of Dp44mT with Human Serum Albumin and Calf Thymus DNA Using Molecular Docking and Spectroscopic Techniques
This response refers to
Analysis of the Interaction of Dp44mT with Human Serum Albumin and Calf Thymus DNA Using Molecular Docking and Spectroscopic Techniques
Di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) exhibits significant antitumor activity. However, the mechanism of its pharmacological interaction with human serum albumin (HSA) and DNA remains poorly understood. Here, we aimed to elucidate the interactions of Dp44mT with HSA and DNA using MTT assays, spectroscopic methods, and molecular docking analysis. Our results indicated that addition of HSA at a ratio of 1:1 did not alter the cytotoxicity of Dp44mT, but did affect the cytotoxicity of the Dp44mT-Cu complex. Data from fluorescence quenching and UV-VIS absorbance measurements demonstrated that Dp44mT could bind to HSA with a moderate affinity (Ka = approximately 104 M−1). CD spectra revealed that Dp44mT could slightly disrupt the secondary structure of HSA. Dp44mT could also interact with Ct-DNA, but had a moderate binding constant (KEB = approximately 104 M−1). Docking studies indicated that the IB site of HSA, but not the IIA and IIIA sites, could be favorable for Dp44mT and that binding of Dp44mT to HSA involved hydrogen bonds and hydrophobic force, consistent with thermodynamic results from spectral investigations. Thus, the moderate binding affinity of Dp44mT with HSA and DNA partially contributed to its antitumor activity and may be preferable in drug design approaches