Descreening of Field Effect in Electrically Gated Nanopores

This modeling work investigates the electrical modulation characteristics of field-effect gated nanopores. Highly nonlinear current modulations are observed in nanopores with non-overlapping electric double layers, including those with pore diameters 100 times the Debye screening length. We attribute this extended field-effect gating to a descreening effect, i.e. the counter-ions do not fully relax to screen the gating potential due to the presence of strong ionic transport

A Simple Regularization-based Algorithm for Learning Cross-Domain Word Embeddings

Learning word embeddings has received a significant amount of attention recently. Often, word embeddings are learned in an unsupervised manner from a large collection of text. The genre of the text typically plays an important role in the effectiveness of the resulting embeddings. How to effectively train word embedding models using data from different domains remains a problem that is underexplored. In this paper, we present a simple yet effective method for learning word embeddings based on text from different domains. We demonstrate the effectiveness of our approach through extensive experiments on various down-stream NLP tasks.Comment: 7 pages, accepted by EMNLP 201

All-trans retinoic acid inhibits proliferation of intestinal epithelial cells by inhibiting expression of the gene encoding Krüppel-like factor 5

AbstractRetinoids are known inhibitors of epithelial cell proliferation. Previous studies indicate that Krüppel-like factor 5 (KLF5) is a pro-proliferative transcription factor. Here, we examined the effect of all-trans retinoid acid (ATRA) on proliferation of the intestinal epithelial cell line, IEC6. Treatment of IEC6 cells with ATRA inhibited their proliferation due to G1 cell cycle arrest. This inhibition was correlated with a decrease in the levels of KLF5 mRNA and promoter activity. In contrast, constitutive expression of KLF5 in stably transfected IEC6 cells with a KLF5-expressing plasmid driven by a viral promoter abrogated the growth inhibitory effect of ATRA. Moreover, ATRA inhibited proliferation of several human colon cancer cell lines with high levels of KLF5 expression but not those with low levels of KLF5 expression. Our results indicate that KLF5 is a potential mediator for the inhibitory effect of ATRA on intestinal epithelial cell proliferation

GEANN: Scalable Graph Augmentations for Multi-Horizon Time Series Forecasting

Encoder-decoder deep neural networks have been increasingly studied for multi-horizon time series forecasting, especially in real-world applications. However, to forecast accurately, these sophisticated models typically rely on a large number of time series examples with substantial history. A rapidly growing topic of interest is forecasting time series which lack sufficient historical data -- often referred to as the ``cold start'' problem. In this paper, we introduce a novel yet simple method to address this problem by leveraging graph neural networks (GNNs) as a data augmentation for enhancing the encoder used by such forecasters. These GNN-based features can capture complex inter-series relationships, and their generation process can be optimized end-to-end with the forecasting task. We show that our architecture can use either data-driven or domain knowledge-defined graphs, scaling to incorporate information from multiple very large graphs with millions of nodes. In our target application of demand forecasting for a large e-commerce retailer, we demonstrate on both a small dataset of 100K products and a large dataset with over 2 million products that our method improves overall performance over competitive baseline models. More importantly, we show that it brings substantially more gains to ``cold start'' products such as those newly launched or recently out-of-stock

Expression of the gut-enriched Krüppel-like factor gene during development and intestinal tumorigenesis

AbstractWe examined the expression of GKLF (gut-enriched Krüppel-like factor), a recently identified zinc finger-containing transcription factor, in mice during development using the ribonuclease protection assay. In the adult, the level of GKLF transcript is abundant throughout the gastrointestinal tract. Between embryonic days 10 and 19 (E10 and E19) of development, the initial level of whole embryo GKLF transcript is low but begins to rise on E13 and peaks on E17. In the newborn, GKLF transcript level is higher in the colon than in the small intestine although the levels in both organs rise with increasing age. Expression of GKLF was also examined in the intestinal tract of the Min mouse, a model of intestinal tumorigenesis. The level of GKLF transcript is significantly decreased in the intestine of Min mice during a period of tumor formation when compared to age-matched control littermates. Our findings indicate that GKLF expression correlates with certain periods of gut development and is down-regulated during intestinal tumorigenesis, suggesting that GKLF may play a role in gut development and/or tumor formation

Krüppel-like factor 5 is a crucial mediator of intestinal tumorigenesis in mice harboring combined ApcMin and KRASV12 mutations

<p>Abstract</p> <p>Background</p> <p>Both mutational inactivation of the adenomatous polyposis coli (<it>APC</it>) tumor suppressor gene and activation of the <it>KRAS </it>oncogene are implicated in the pathogenesis of colorectal cancer. Mice harboring a germline <it>Apc</it>^{<it>Min </it>}mutation or intestine-specific expression of the <it>KRAS</it>^<it>V</it>12gene have been developed. Both mouse strains develop spontaneous intestinal tumors, including adenoma and carcinoma, though at a different age. The zinc finger transcription factor Krüppel-like factor 5 (KLF5) has previously been shown to promote proliferation of intestinal epithelial cells and modulate intestinal tumorigenesis. Here we investigated the <it>in vivo </it>effect of <it>Klf5 </it>heterozygosity on the propensity of <it>Apc</it>^<it>Min</it>/<it>KRAS</it>^<it>V</it>12double transgenic mice to develop intestinal tumors.</p> <p>Results</p> <p>At 12 weeks of age, <it>Apc</it>^<it>Min</it>/<it>KRAS</it>^<it>V</it>12mice had three times as many intestinal tumors as <it>Apc</it>^{<it>Min </it>}mice. This increase in tumor number was reduced by 92% in triple transgenic <it>Apc</it>^<it>Min</it>/<it>KRAS</it>^<it>V</it>12/<it>Klf5</it>^+/-mice. The reduction in tumor number in <it>Apc</it>^<it>Min</it>/<it>KRAS</it>^<it>V</it>12/<it>Klf5</it>^+/-mice was also statistically significant compared to <it>Apc</it>^{<it>Min </it>}mice alone, with a 75% decrease. Compared with <it>Apc</it>^<it>Min</it>/<it>KRAS</it>^<it>V</it>12, tumors from both <it>Apc</it>^<it>Min</it>/<it>KRAS</it>^<it>V</it>12/<it>Klf5</it>^+/-and <it>Apc</it>^{<it>Min </it>}mice were smaller. In addition, tumors from <it>Apc</it>^{<it>Min </it>}mice were more distally distributed in the intestine as contrasted by the more proximal distribution in <it>Apc</it>^<it>Min</it>/<it>KRAS</it>^<it>V</it>12and <it>Apc</it>^<it>Min</it>/<it>KRAS</it>^<it>V</it>12/<it>Klf5</it>^+/-mice. Klf5 levels in the normal-appearing intestinal mucosa were higher in both <it>Apc</it>^{<it>Min </it>}and <it>Apc</it>^<it>Min</it>/<it>KRAS</it>^<it>V</it>12mice but were attenuated in <it>Apc</it>^<it>Min</it>/<it>KRAS</it>^<it>V</it>12/<it>Klf5</it>^+/-mice. The levels of β-catenin, cyclin D1 and Ki-67 were also reduced in the normal-appearing intestinal mucosa of <it>Apc</it>^<it>Min</it>/<it>KRAS</it>^<it>V</it>12/<it>Klf5</it>^+/-mice when compared to <it>Apc</it>^<it>Min</it>/<it>KRAS</it>^<it>V</it>12mice. Levels of pMek and pErk1/2 were elevated in the normal-appearing mucosa of <it>Apc</it>^<it>Min</it>/<it>KRAS</it>^<it>V</it>12mice and modestly reduced in Apc^Min/<it>KRAS</it>^<it>V</it>12/<it>Klf5</it>^+/-mice. Tumor tissues displayed higher levels of both Klf5 and β-catenin, irrespective of the mouse genotype from which tumors were derived.</p> <p>Conclusions</p> <p>Results of the current study confirm the cumulative effect of <it>Apc </it>loss and oncogenic <it>KRAS </it>activation on intestinal tumorigenesis. The drastic reduction in tumor number and size due to <it>Klf5 </it>heterozygosity in <it>Apc</it>^<it>Min</it>/<it>KRAS</it>^<it>V</it>12mice indicate a critical function of KLF5 in modulating intestinal tumor initiation and progression.</p

Krüppel-like factor 5 is an important mediator for lipopolysaccharide-induced proinflammatory response in intestinal epithelial cells

Lipopolysaccharide (LPS) is a bacterially-derived endotoxin that elicits a strong proinflammatory response in intestinal epithelial cells. It is well established that LPS activates this response through NF-κB. In addition, LPS signals through the mitogen-activated protein kinase (MAPK) pathway. We previously demonstrated that the Krüppel-like factor 5 [KLF5; also known as intestine-enriched Krüppel-like factor (IKLF)] is activated by the MAPK. In the current study, we examined whether KLF5 mediates the signaling cascade elicited by LPS. Treatment of the intestinal epithelial cell line, IEC6, with LPS resulted in a dose- and time-dependent increase in KLF5 messenger RNA (mRNA) and protein levels. Concurrently, mRNA levels of the p50 and p65 subunits of NF-κB were increased by LPS treatment. Pretreatment with the MAPK inhibitor, U0126, or the LPS antagonist, polymyxin B, resulted in an attenuation of KLF5, p50 and p65 NF-κB subunit mRNA levels from LPS treatment. Importantly, suppression of KLF5 by small interfering RNA (siRNA) resulted in a reduction in p50 and p65 subunit mRNA levels and NF-κB DNA binding activity in response to LPS. LPS treatment also led to an increase in secretion of TNF-α and IL-6 from IEC6, both of which were reduced by siRNA inhibition of KLF5. In addition, intercellular adhesion molecule-1 (ICAM-1) levels were increased in LPS-treated IEC6 cells and this increase was associated with increased adhesion of Jurkat lymphocytes to IEC6. The induction of ICAM-1 expression and T cell adhesion to IEC6 by LPS were both abrogated by siRNA inhibition of KLF5. These results indicate that KLF5 is an important mediator for the proinflammatory response elicited by LPS in intestinal epithelial cells