3,330 research outputs found

    Identification and evolutionary analysis of novel exons and alternative splicing events using cross-species EST-to-genome comparisons in human, mouse and rat

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    BACKGROUND: Alternative splicing (AS) is important for evolution and major biological functions in complex organisms. However, the extent of AS in mammals other than human and mouse is largely unknown, making it difficult to study AS evolution in mammals and its biomedical implications. RESULTS: Here we describe a cross-species EST-to-genome comparison algorithm (ENACE) that can identify novel exons for EST-scanty species and distinguish conserved and lineage-specific exons. The identified exons represent not only novel exons but also evolutionarily meaningful AS events that are not previously annotated. A genome-wide AS analysis in human, mouse and rat using ENACE reveals a total of 758 novel cassette-on exons and 167 novel retained introns that have no EST evidence from the same species. RT-PCR-sequencing experiments validated ~50 ~80% of the tested exons, indicating high presence of exons predicted by ENACE. ENACE is particularly powerful when applied to closely related species. In addition, our analysis shows that the ENACE-identified AS exons tend not to pass the nonsynonymous-to-synonymous substitution ratio test and not to contain protein domain, implying that such exons may be under positive selection or relaxed negative selection. These AS exons may contribute to considerable inter-species functional divergence. Our analysis further indicates that a large number of exons may have been gained or lost during mammalian evolution. Moreover, a functional analysis shows that inter-species divergence of AS events may be substantial in protein carriers and receptor proteins in mammals. These exons may be of interest to studies of AS evolution. The ENACE programs and sequences of the ENACE-identified AS events are available for download. CONCLUSION: ENACE can identify potential novel cassette exons and retained introns between closely related species using a comparative approach. It can also provide information regarding lineage- or species-specificity in transcript isoforms, which are important for evolutionary and functional studies

    An Integrated Multiechelon Logistics Model with Uncertain Delivery Lead Time and Quality Unreliability

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    Nowadays, in order to achieve advantages in supply chain management, how to keep inventory in adequate level and how to enhance customer service level are two critical practices for decision makers. Generally, uncertain lead time and defective products have much to do with inventory and service level. Therefore, this study mainly aims at developing a multiechelon integrated just-in-time inventory model with uncertain lead time and imperfect quality to enhance the benefits of the logistics model. In addition, the Ant Colony Algorithm (ACA) is established to determine the optimal solutions. Moreover, based on our proposed model and analysis, the ACA is more efficient than Particle Swarm Optimization (PSO) and Lingo in SMEIJI model. An example is provided in this study to illustrate how production run and defective rate have an effect on system costs. Finally, the results of our research could provide some managerial insights which support decision makers in real-world operations

    Dish Discovery via Word Embeddings on Restaurant Reviews

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    ABSTRACT This paper proposes a novel framework for automatic dish discovery via word embeddings on restaurant reviews. We collect a dataset of user reviews from Yelp and parse the reviews to extract dish words. Then, we utilize the processed reviews as training texts to learn the embedding vectors of words via the skip-gram model. In the paper, a nearestneighbor like score function is proposed to rank the dishes based on their learned representations. We brief some analyses on the preliminary experiments and present a web-based visualization at http://clip.csie.org/yelp/. Keywords dish discovery, word embeddings, dish-word extraction BACKGROUND With the growth of social media, corporations, such as Yelp, have accumulated a great number of user generated content (UGC). In the literature, some studies have been conducted with a perspective of finding critical information hidden in the content METHODOLOGY Copyright held by the author(s). RecSys 2016 Poster Proceedings, September 15-19, 2016, USA, Boston. Our methodology mainly consists of three parts: 1) dishword recognition, 2) word embedding learning, and 3) dish score calculation. As alluded to earlier, UGC usually incorporates a degree of noise and different language usages; therefore, extracting dish names from user reviews is a complicated task. For example, observed from the dataset, users tend not to write the full name of a dish in their reviews; instead, the last word or the last two words are often written in the reviews. To grapple with this issue, we use regular expressions (regexps) to extract dish names from the user reviews. However, this also give rise to an issue that a certain dish in a restaurant may be of the same name in other restaurants, which may induce the problem of ambiguity and lower the accuracy of matching the correct dish name. So, we attach a dish name with its restaurant name to solve the ambiguity problem. We then utilize the collection of processed reviews as training texts to learn embeddings of each word in the reviews via a continuous space language model, the skip-gram model. After the training phase, each word (including every dish) is represented by an n-dimensional vector (called the embedding of this word). Inspired by the k-nearest neighbors algorithm, we define the score for every dish d as: where , m is the total number of positive sentiment words considered, λi (i = 1, · · · , m) is a weighting parameter. In addition, si denotes the i-nearest positive sentiment words of the given dish d, and w d , ws i ∈ R n are the vector representations of the dish d and the sentiment word si, respectively. In an extreme case (1) of λm = 1 and λi = 0 for i = 1, · · · , m − 1, this score function implements the concept of the average Euclidean distance between a dish and all the positive sentiment words; while in the case (2) λ1 = 1 and λi = 0 for i = 2, · · · , m, the scored is obtained with the closest positive sentiment words to the dish. EXPERIMENTS Our preliminary experiments involve a real-world restaurant review dataset collected from Yelp Data Challenge

    Thermal evolution of spin excitations in honeycomb Ising antiferromagnetic FePSe3

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    We use elastic and inelastic neutron scattering (INS) to study the antiferromagnetic (AF) phase transitions and spin excitations in the two-dimensional (2D) zig-zag antiferromagnet FePSe3_3. By determining the magnetic order parameter across the AF phase transition, we conclude that the AF phase transition in FePSe3_3 is first-order in nature. In addition, our INS measurements reveal that the spin waves in the AF ordered state have a large easy-axis magnetic anisotropy gap, consistent with an Ising Hamiltonian, and possible biquadratic magnetic exchange interactions. On warming across TNT_N, we find that dispersive spin excitations associated with three-fold rotational symmetric AF fluctuations change into FM spin fluctuations above TNT_N. These results suggest that the first-order AF phase transition in FePSe3_3 may arise from the competition between C3C_3 symmetric AF and C1C_1 symmetric FM spin fluctuations around TNT_N, in place of a conventional second-order AF phase transition

    15,16-Dihydrotanshinone I, a Compound of Salvia miltiorrhiza Bunge, Induces Apoptosis through Inducing Endoplasmic Reticular Stress in Human Prostate Carcinoma Cells

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    5,16-dihydrotanshinone I (DHTS) is extracted from Salvia miltiorrhiza Bunge (tanshen root) and was found to be the most effective compound of tanshen extracts against breast cancer cells in our previous studies. However, whether DHTS can induce apoptosis through an endoplasmic reticular (ER) stress pathway was examined herein. In this study, we found that DHTS significantly inhibited the proliferation of human prostate DU145 carcinoma cells and induced apoptosis. DHTS was able to induce ER stress as evidenced by the upregulation of glucose regulation protein 78 (GRP78/Bip) and CAAT/enhancer binding protein homologous protein/growth arrest- and DNA damage-inducible gene 153 (CHOP/GADD153), as well as increases in phosphorylated eukaryotic initiation factor 2α (eIF2α), c-jun N-terminal kinase (JNK), and X-box-binding protein 1 (XBP1) mRNA splicing forms. DHTS treatment also caused significant accumulation of polyubiquitinated proteins and hypoxia-inducible factor (HIF)-1α, indicating that DHTS might be a proteasome inhibitor that is known to induce ER stress or enhance apoptosis caused by the classic ER stress-dependent mechanism. Moreover, DHTS-induced apoptosis was reversed by salubrinal, an ER stress inhibitor. Results suggest that DHTS can induce apoptosis of prostate carcinoma cells via induction of ER stress and/or inhibition of proteasome activity, and may have therapeutic potential for prostate cancer patients

    Switch activation of PI-PLC downstream signals in activated macrophages with wortmannin

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    AbstractPhosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2) has been known to serve as a substrate for phosphatidylinositol 3-kinase (PI3K) and phosphoinositide-specific phospholipase C (PI-PLC), which can produce PtdIns(3,4,5)P3 and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and diacylglycerol (DAG), respectively. In this study, we elucidated the role of PI-PLC during the LPS-activated mouse macrophages RAW264.7 treated with PI3K inhibitor wortmannin. First, wortmannin treatment enhanced Ins(1,4,5)P3 production and iNOS expression in LPS-activated macrophages. Inhibition of PI3K by p85 siRNA also showed an enhancement of iNOS expression. On the other hand, overexpression of PI3K by ras-p110 expression plasmid significantly decreased iNOS expression in LPS-activated macrophages. In addition, overexpression of wild-type or dominant-negative Akt expression plasmid did not affect the iNOS expression in LPS-activated macrophages. Second, treatment of PI-PLC inhibitor U73122 reversed the enhancement of iNOS expression, the increase of phosphorylation level of ERK, JNK and p38, and the increase of AP-1-dependent gene expression in wortmannin-treated and LPS-activated macrophages. However, NF-κB activity determined by EMSA assay and reporter plasmid assay did not change during LPS-activated macrophages with or without wortmannin. We propose that the inhibition of PI3K by wortmannin in mouse macrophages enhances the PI-PLC downstream signals, and subsequently increases the LPS induction of iNOS expression independently of Akt pathway

    SDSS J013127.34-032100.1: A newly discovered radio-loud quasar at z=5.18z=5.18 with extremely high luminosity

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    Only very few z>5 quasars discovered to date are radio-loud, with a radio-to-optical flux ratio (radio-loudness parameter) higher than 10. Here we report the discovery of an optically luminous radio-loud quasar, SDSS J013127.34-032100.1 (J0131-0321 in short), at z=5.18+-0.01 using the Lijiang 2.4m and Magellan telescopes. J0131-0321 has a spectral energy distribution consistent with that of radio-loud quasars. With an i-band magnitude of 18.47 and radio flux density of 33 mJy, its radio-loudness parameter is ~100. The optical and near-infrared spectra taken by Magellan enable us to estimate its bolometric luminosity to be L_bol ~ 1.1E48 erg/s, approximately 4.5 times greater than that of the most distant quasar known to date. The black hole mass of J0131-0321 is estimated to be 2.7E9 solar masses, with an uncertainty up to 0.4 dex. Detailed physical properties of this high-redshift, radio-loud, potentially super-Eddington quasar can be probed in the future with more dedicated and intensive follow-up observations using multi-wavelength facilities.Comment: 5 pages, 3 figures, accepted to ApJ

    An Epidemiological Study of Concomitant Use of Chinese Medicine and Antipsychotics in Schizophrenic Patients: Implication for Herb-Drug Interaction

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    Background: Herb-drug interactions are an important issue in drug safety and clinical practice. The aim of this epidemiological study was to characterize associations of clinical outcomes with concomitant herbal and antipsychotic use in patients with schizophrenia. Methods and Findings: In this retrospective, cross-sectional study, 1795 patients with schizophrenia who were randomly selected from 17 psychiatric hospitals in China were interviewed face-to-face using a structured questionnaire. Association analyses were conducted to examine correlates between Chinese medicine (CM) use and demographic, clinical variables, antipsychotic medication mode, and clinical outcomes. The prevalence of concomitant CM and antipsychotic treatment was 36.4% [95% confidence interval (95% CI) 34.2%-38.6%]. Patients using concomitant CM had a significantly greater chance of improved outcomes than non-CM use (61.1% vs. 34.3%, OR = 3.44, 95% CI 2.80-4.24). However, a small but significant number of patients treated concomitantly with CM had a greater risk of developing worse outcomes (7.2% vs. 4.4%, OR = 2.06, 95% CI 2.06-4.83). Significant predictors for concomitant CM treatment-associated outcomes were residence in urban areas, paranoid psychosis, and exceeding 3 months of CM use. Herbal medicine regimens containing Radix Bupleuri, Fructus Gardenia, Fructus Schisandrae, Radix Rehmanniae, Akebia Caulis, and Semen Plantaginis in concomitant use with quetiapine, clozapine, and olanzepine were associated with nearly 60% of the risk of adverse outcomes. Conclusions: Concomitant herbal and antipsychotic treatment could produce either beneficial or adverse clinical effects in schizophrenic population. Potential herb-drug pharmacokinetic interactions need to be further evaluated. © 2011 Zhang et al.published_or_final_versio
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