An Image Dataset for Benchmarking Recommender Systems with Raw Pixels

Recommender systems (RS) have achieved significant success by leveraging explicit identification (ID) features. However, the full potential of content features, especially the pure image pixel features, remains relatively unexplored. The limited availability of large, diverse, and content-driven image recommendation datasets has hindered the use of raw images as item representations. In this regard, we present PixelRec, a massive image-centric recommendation dataset that includes approximately 200 million user-image interactions, 30 million users, and 400,000 high-quality cover images. By providing direct access to raw image pixels, PixelRec enables recommendation models to learn item representation directly from them. To demonstrate its utility, we begin by presenting the results of several classical pure ID-based baseline models, termed IDNet, trained on PixelRec. Then, to show the effectiveness of the dataset's image features, we substitute the itemID embeddings (from IDNet) with a powerful vision encoder that represents items using their raw image pixels. This new model is dubbed PixelNet.Our findings indicate that even in standard, non-cold start recommendation settings where IDNet is recognized as highly effective, PixelNet can already perform equally well or even better than IDNet. Moreover, PixelNet has several other notable advantages over IDNet, such as being more effective in cold-start and cross-domain recommendation scenarios. These results underscore the importance of visual features in PixelRec. We believe that PixelRec can serve as a critical resource and testing ground for research on recommendation models that emphasize image pixel content. The dataset, code, and leaderboard will be available at https://github.com/westlake-repl/PixelRec

Yes-associated protein 1 is required for proliferation and function of bovine granulosa cells in vitro

Yes-associated protein 1 (YAP1) is a major component of the Hippo signaling pathway. Although the exact extracellular signals that control the Hippo pathway are currently unknown, increasing evidence supports a critical role for the Hippo pathway in embryonic development, regulation of organ size, and carcinogenesis. Granulosa cells (GCs) within the ovarian follicle proliferate and produce steroids and growth factors, which facilitate the growth of follicle and maturation of the oocyte.We hypothesize that YAP1 plays a role in proliferation and estrogen secretion of GCs. In the current study, we examined the expression of the Hippo signaling pathway in bovine ovaries and determined whether it was important for GC proliferation and estrogen production. Mammalian STE20-like protein kinase 1 (MST1) and large tumor suppressor kinase 2 (LATS2) were identified as prominent upstream components of the Hippo pathway expressed in granulosa and theca cells of the follicle and large and small cells of the corpus luteum. Immunohistochemistry revealed that YAP1 was localized to the nucleus of growing follicles. In vitro, nuclear localization of the downstream Hippo signaling effector proteins YAP1 and transcriptional co-activator with PDZbinding motif (TAZ) was inversely correlated with GC density, with greater nuclear localization under conditions of low cell density. Treatment with verteporfin and siRNA targeting YAP1 or TAZ revealed a critical role for these transcriptional co-activators in GC proliferation. Furthermore, knockdown of YAP1 in GCs inhibited follicle-stimulating hormone (FSH)-induced estradiol biosynthesis. The data indicate that Hippo pathway transcription co-activators YAP1/TAZ play an important role in GC proliferation and estradiol synthesis, two processes necessary for maintaining normal follicle development

Pluripotent Stem Cells Cartilage Repair Using Human Embryonic Stem Cell-Derived Chondroprogenitors

ABSTRACT In initial work, we developed a 14-day culture protocol under potential GMP, chemically defined conditions to generate chondroprogenitors from human embryonic stem cells (hESCs). The present study was undertaken to investigate the cartilage repair capacity of these cells. The chondrogenic protocol was optimized and validated with gene expression profiling. The protocol was also applied successfully to two lines of induced pluripotent stem cells (iPSCs). Chondrogenic cells derived from hESCs were encapsulated in fibrin gel and implanted in osteochondral defects in the patella groove of nude rats, and cartilage repair was evaluated by histomorphology and immunocytochemistry. Genes associated with chondrogenesis were upregulated during the protocol, and pluripotency-related genes were downregulated. Aggregation of chondrogenic cells was accompanied by high expression of SOX9 and strong staining with Safranin O. Culture with PluriSln1 was lethal for hESCs but was tolerated by hESC chondrogenic cells, and no OCT4-positive cells were detected in hESC chondrogenic cells. iPSCs were also shown to generate chondroprogenitors in this protocol. Repaired tissue in the defect area implanted with hESC-derived chondrogenic cells was stained for collagen II with little collagen I, but negligible collagen II was observed in the fibrin-only controls. Viable human cells were detected in the repair tissue at 12 weeks. The results show that chondrogenic cells derived from hESCs, using a chemically defined culture system, when implanted in focal defects were able to promote cartilage repair. This is a first step in evaluating these cells for clinical application for the treatment of cartilage lesions. STEM CELL

Learning Travel Time Distributions with Deep Generative Model

Travel time estimation of a given route with respect to real-time traffic condition is extremely useful for many applications like route planning. We argue that it is even more useful to estimate the travel time distribution, from which we can derive the expected travel time as well as the uncertainty. In this paper, we develop a deep generative model - DeepGTT - to learn the travel time distribution for any route by conditioning on the real-time traffic. DeepGTT interprets the generation of travel time using a three-layer hierarchical probabilistic model. In the first layer, we present two techniques, amortization and spatial smoothness embeddings, to share statistical strength among different road segments; a convolutional neural net based representation learning component is also proposed to capture the dynamically changing real-time traffic condition. In the middle layer, a nonlinear factorization model is developed to generate auxiliary random variable i.e., speed. The introduction of this middle layer separates the statical spatial features from the dynamically changing real-time traffic conditions, allowing us to incorporate the heterogeneous influencing factors into a single model. In the last layer, an attention mechanism based function is proposed to collectively generate the observed travel time. DeepGTT describes the generation process in a reasonable manner, and thus it not only produces more accurate results but also is more efficient. On a real-world large-scale data set, we show that DeepGTT produces substantially better results than state-of-the-art alternatives in two tasks: travel time estimation and route recovery from sparse trajectory data

Functional nicotinic and muscarinic receptors on mesenchymal stem cells

Mesenchymal stem cells (MSCs) are under the control of a large number of signaling systems. In this study, the presence and functionality of the acetylcholine (ACh) signaling system in MSCs was examined. We detected the expression of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and the presence of ACh in MSCs. MSCs also expressed the nicotinic acetylcholine receptor subunits α3, α5, α7, and the muscarinic acetylcholine receptor 2 (M2-receptor). The M2-receptor and the nicotinic α7 receptor subunits were expressed on distinct subpopulations of cells, indicating differential regulation of cholinergic signaling between MSCs. Stimulation of MSCs with the nicotinic receptor agonist nicotine and the muscarinic receptor agonist muscarine induced immediate and transient increases in intracellular Ca2+ concentration. Furthermore, muscarine had an inhibiting effect on the production of the intracellular signaling molecule cyclic adenosine 3′,5′-monophosphate (cAMP). The AChE inhibitor chlorpyrifos, which is widely used as an agricultural insecticide, had similar effects on intracellular Ca2+ and cAMP in MSCs. Nicotine, muscarine, and chlorpyrifos induced the phosphorylation of extracellular signal-regulated kinases 1 and 2. This study demonstrates that several components of a cholinergic signaling system are present and functional in MSCs. Environmental compounds such as nicotine and agricultural insecticides can interfere with this system and may affect cellular processes in the MSC

IL-2R Signaling Is Essential for Functional Maturation of Regulatory T Cells during Thymic Development

CD4(+) Foxp3(+) Tregs are an independent cell lineage and their developmental progression during thymic development depends on IL-2R signaling. However, the role of IL-2R signaling during thymic Treg development remains only partially understood. The current study assessed the contribution of IL-2 in the expansion and functional programming of developing Tregs. In the absence of IL-2Rβ signaling, predominately CD4(+) CD25(-) Foxp3(lo) T cells were found and these cells exhibited somewhat lower expression of the proliferative marker Ki67. These immature Tregs, which represent products of failed development, were also found in normal mice and characterized by markedly lower expression of several Treg functional molecules. IL-2R signaling, therefore, is required for the progression, functional programming, and expansion of Tregs during thymic development. An IL-2R signaling mutant that lowers STAT5 activation readily supported Treg functional programming but Treg proliferation remained somewhat impaired. The requirement for IL-2 during thymic Treg expansion was best illustrated in mixed chimeras where the Tregs with mutant IL-2Rs were forced to compete with WT Tregs during their development. Tregs with impaired IL-2R signaling were more prevalent in the thymus than spleen in these competitive experiments. The general effectiveness of mutant IL-2Rs to support thymic Treg development is partially accounted for by a heighten capacity of thymic Tregs to respond to IL-2. Overall our data support a model where limiting IL-2R signaling is amplified by thymic Tregs to readily support their development and functional programming whereas these same conditions are not sufficient to support peripheral Treg homeostasis

Yes-associated protein 1 is required for proliferation and function of bovine granulosa cells in vitro

Yes-associated protein 1 (YAP1) is a major component of the Hippo signaling pathway. Although the exact extracellular signals that control the Hippo pathway are currently unknown, increasing evidence supports a critical role for the Hippo pathway in embryonic development, regulation of organ size, and carcinogenesis. Granulosa cells (GCs) within the ovarian follicle proliferate and produce steroids and growth factors, which facilitate the growth of follicle and maturation of the oocyte.We hypothesize that YAP1 plays a role in proliferation and estrogen secretion of GCs. In the current study, we examined the expression of the Hippo signaling pathway in bovine ovaries and determined whether it was important for GC proliferation and estrogen production. Mammalian STE20-like protein kinase 1 (MST1) and large tumor suppressor kinase 2 (LATS2) were identified as prominent upstream components of the Hippo pathway expressed in granulosa and theca cells of the follicle and large and small cells of the corpus luteum. Immunohistochemistry revealed that YAP1 was localized to the nucleus of growing follicles. In vitro, nuclear localization of the downstream Hippo signaling effector proteins YAP1 and transcriptional co-activator with PDZbinding motif (TAZ) was inversely correlated with GC density, with greater nuclear localization under conditions of low cell density. Treatment with verteporfin and siRNA targeting YAP1 or TAZ revealed a critical role for these transcriptional co-activators in GC proliferation. Furthermore, knockdown of YAP1 in GCs inhibited follicle-stimulating hormone (FSH)-induced estradiol biosynthesis. The data indicate that Hippo pathway transcription co-activators YAP1/TAZ play an important role in GC proliferation and estradiol synthesis, two processes necessary for maintaining normal follicle development