Towards Explainable Conversational Recommender Systems

Explanations in conventional recommender systems have demonstrated benefits in helping the user understand the rationality of the recommendations and improving the system's efficiency, transparency, and trustworthiness. In the conversational environment, multiple contextualized explanations need to be generated, which poses further challenges for explanations. To better measure explainability in conversational recommender systems (CRS), we propose ten evaluation perspectives based on concepts from conventional recommender systems together with the characteristics of CRS. We assess five existing CRS benchmark datasets using these metrics and observe the necessity of improving the explanation quality of CRS. To achieve this, we conduct manual and automatic approaches to extend these dialogues and construct a new CRS dataset, namely Explainable Recommendation Dialogues (E-ReDial). It includes 756 dialogues with over 2,000 high-quality rewritten explanations. We compare two baseline approaches to perform explanation generation based on E-ReDial. Experimental results suggest that models trained on E-ReDial can significantly improve explainability while introducing knowledge into the models can further improve the performance. GPT-3 in the in-context learning setting can generate more realistic and diverse movie descriptions. In contrast, T5 training on E-ReDial can better generate clear reasons for recommendations based on user preferences. E-ReDial is available at https://github.com/Superbooming/E-ReDial

Sphingosine kinase 1 and 2 regulate the capacity of mesangial cells to resist apoptotic stimuli in an opposing manner

Sphingosine kinases (SKs) are key enzymes regulating the production of sphingosine-1-phosphate (S1P), which determines important cell responses including cell growth and death. Here we show that renal mesangial cells isolated from wild-type, SK-1-/-, and SK-2-/- mice show a differential response to apoptotic stimuli. Wild-type mesangial cells responded to staurosporine with increased DNA fragmentation and caspase-3 processing, which was enhanced in SK-1-/- cells. In contrast, SK-2-/- cells were highly resistant to staurosporine-induced apoptosis. Furthermore, the basal phosphorylation and activity of the anti-apoptotic protein kinase B (PKB) and of its substrate Bad were decreased in SK-1-/- but not in SK-2-/- cells. Upon staurosporine treatment, phosphorylation of PKB and Bad decreased in wild-type and SK-1-/- cells, but remained high in SK-2-/- cells. In addition, the anti-apoptotic Bcl-XL was significantly upregulated in SK-2-/- cells, which may further contribute to the protective state of these cells. In summary, our data show that SK-1 and SK-2 have opposite effects on the capacity of mesangial cells to resist apoptotic stimuli. This is due to differential modulation of the PKB/Bad pathway and of Bcl-XL expression. Thus, subtype-selective targeting of SKs will be critical when considering these enzymes as therapeutic targets for the treatment of inflammation or cance

Glucose-fueled Micromotors with Highly Efficient Visible Light Photocatalytic Propulsion

Synthetic micro/nanomotors fueled by glucose are highly desired for numerous practical applications because of the biocompatibility of their required fuel. However, currently all of the glucose-fueled micro/nanomotors are based on enzyme-catalytic-driven mechanisms, which usually suffer from strict operation conditions and weak propulsion characteristics that greatly limit their applications. Here, we report a highly efficient glucose-fueled cuprous oxide@N-doped carbon nanotube (Cu_2O@N-CNT) micromotor, which can be activated by environment-friendly visible-light photocatalysis. The speeds of such Cu_2O@N-CNT micromotors can reach up to 18.71 μm/s, which is comparable to conventional Pt-based catalytic Janus micromotors usually fueled by toxic H_2O_2 fuel. In addition, the velocities of such motors can be efficiently regulated by multiple approaches, such as adjusting the N-CNT content within the micromotors, glucose concentrations, or light intensities. Furthermore, the Cu_2O@N-CNT micromotors exhibit a highly controllable negative phototaxis behavior (moving away from light sources). Such motors with outstanding propulsion in biological environments and wireless, repeatable, and light-modulated three-dimensional motion control are extremely attractive for future practical applications

Correction to: Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits

Erratum for Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits. [BMC Med Genomics. 2019

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

LRP-6 is a coreceptor for multiple fibrogenic signaling pathways in pericytes and myofibroblasts that are inhibited by DKK-1

Fibrosis of vital organs is a major public health problem with limited therapeutic options. Mesenchymal cells including microvascular mural cells (pericytes) are major progenitors of scar-forming myofibroblasts in kidney and other organs. Here we show pericytes in healthy kidneys have active WNT/beta-catenin signaling responses that are markedly up-regulated following kidney injury. Dickkopf-related protein 1 (DKK-1), a ligand for the WNT coreceptors low-density lipoprotein receptor-related proteins 5 and 6 (LRP-5 and LRP-6) and an inhibitor of WNT/beta-catenin signaling, effectively inhibits pericyte activation, detachment, and transition to myofibroblasts in vivo in response to kidney injury, resulting in attenuated fibrogenesis, capillary rarefaction, and inflammation. DKK-1 blocks activation and proliferation of established myofibroblasts in vitro and blocks pericyte proliferation to PDGF, pericyte migration, gene activation, and cytoskeletal reorganization to TGF-beta or connective tissue growth factor. These effects are largely independent of inhibition of downstream beta-catenin signaling. DKK-1 acts predominantly by inhibiting PDGF-, TGF-beta-, and connective tissue growth factor-activated MAPK and JNK signaling cascades, acting via LRP-6 with associated WNT ligand. Biochemically, LRP-6 interacts closely with PDGF receptor beta and TGF-beta receptor 1 at the cell membrane, suggesting that it may have roles in pathways other than WNT/beta-catenin. In summary, DKK-1 blocks many of the changes in pericytes required for myofibroblast transition and attenuates established myofibroblast proliferation/activation by mechanisms dependent on LRP-6 and WNT ligands but not the downstream beta-catenin pathway

A novel mode of action of the putative sphingosine kinase inhibitor 2-(p-hydroxyanilino)-4-(p-chlorophenyl) thiazole (SKI II): induction of lysosomal sphingosine kinase 1 degradation

Sphingosine kinase 1 (SK1) is a key enzyme in the generation of sphingosine 1-phosphate (S1P) which critically regulates a variety of important cell responses such as proliferation and migration. Therefore, inhibition of SK-1 has been suggested to be an attractive approach to treat tumor growth and metastasis formation