2,132 research outputs found

    Regulation of nuclear-cytoplasmic shuttling and function of Family with sequence similarity 13, member A (Fam13a), by B56-containing PP2As and Akt

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    Recent genome-wide association studies reveal that the FAM13A gene is associated with human lung function and a variety of lung diseases, including chronic obstructive pulmonary disease, asthma, lung cancer, and pulmonary fibrosis. The biological functions of Fam13a, however, have not been studied. In an effort to identify novel substrates of B56-containing PP2As, we found that B56-containing PP2As and Akt act antagonistically to control reversible phosphorylation of Fam13a on Ser-322. We show that Ser-322 phosphorylation acts as a molecular switch to control the subcellular distribution of Fam13a. Fam13a shuttles between the nucleus and cytoplasm. When Ser-322 is phosphorylated by Akt, the binding between Fam13a and 14-3-3 is enhanced, leading to cytoplasmic sequestration of Fam13a. B56-containing PP2As dephosphorylate phospho-Ser-322 and promote nuclear localization of Fam13a. We generated Fam13a-knockout mice. Fam13a-mutant mice are viable and healthy, indicating that Fam13a is dispensable for embryonic development and physiological functions in adult animals. Intriguingly, Fam13a has the ability to activate the Wnt pathway. Although Wnt signaling remains largely normal in Fam13a-knockout lungs, depletion of Fam13a in human lung cancer cells causes an obvious reduction in Wnt signaling activity. Our work provides important clues to elucidating the mechanism by which Fam13a may contribute to human lung diseases

    Context-lumpable stochastic bandits

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    We consider a contextual bandit problem with SS contexts and AA actions. In each round t=1,2,t=1,2,\dots the learner observes a random context and chooses an action based on its past experience. The learner then observes a random reward whose mean is a function of the context and the action for the round. Under the assumption that the contexts can be lumped into rmin{S,A}r\le \min\{S ,A \} groups such that the mean reward for the various actions is the same for any two contexts that are in the same group, we give an algorithm that outputs an ϵ\epsilon-optimal policy after using at most O~(r(S+A)/ϵ2)\widetilde O(r (S +A )/\epsilon^2) samples with high probability and provide a matching Ω~(r(S+A)/ϵ2)\widetilde\Omega(r (S +A )/\epsilon^2) lower bound. In the regret minimization setting, we give an algorithm whose cumulative regret up to time TT is bounded by O~(r3(S+A)T)\widetilde O(\sqrt{r^3(S +A )T}). To the best of our knowledge, we are the first to show the near-optimal sample complexity in the PAC setting and O~(poly(r)(S+K)T)\widetilde O(\sqrt{{poly}(r)(S+K)T}) minimax regret in the online setting for this problem. We also show our algorithms can be applied to more general low-rank bandits and get improved regret bounds in some scenarios

    A Comparative Study of Wireless Protocols: Bluetooth, UWB, ZigBee, and Wi-Fi

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    (UWB, over IEEE 802.15.3), ZigBee (over IEEE 802.15.4), and Wi-Fi (over IEEE 802.11) are four protocol standards for short-range wireless communications with low power consumption. From an application point of view, Bluetooth is intended for a cordless mouse, keyboard, and hands-free headset, UWB is oriented to high-bandwidth multimedia links, ZigBee is designed for reliable wirelessly networked monitoring and control networks, while Wi-Fi is directed at computer-to-computer connections as an extension or substitution of cabled networks. In this paper, we provide a study of these popular wireless communication standards, evaluating their main features and behaviors in terms of various metrics, including the transmission time, data coding efficiency, complexity, and power consumption. It is believed that the comparison presented in this paper would benefit application engineers in selecting an appropriate protocol

    Reliability of 95% confidence interval revealed by expected quality-of-life scores: an example of nasopharyngeal carcinoma patients after radiotherapy using EORTC QLQ-C 30

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    <p>Abstract</p> <p>Background</p> <p>Many researchers use observed questionnaire scores to evaluate score reliability and to make conclusions and inferences regarding quality-of-life outcomes. The amount of false alarms from medical diagnoses that would be avoided if observed scores were substituted with expected scores is interesting, and understanding these differences is important for the care of cancer patients. Using expected scores to estimate the reliability of 95% confidence intervals (CIs) is rarely reported in published papers. We investigated the reliability of patient responses to a quality-of-life questionnaire and made recommendations for future studies of the quality of life of patients.</p> <p>Methods</p> <p>A total of 115 patients completed the EORTC core questionnaire QLQ-C30 (version 3) after radiotherapy. The observed response scores, assumed to be one-dimensional, were summed and transformed into expected scores using the Rasch rating scale model with WINSTEPS software. A series of simulations was performed using a unified bootstrap procedure after manipulating scenarios with different questionnaire lengths and patient numbers to estimate the reliability at 95% confidence intervals. Skewness analyses of the 95% CIs were compared to detect different effects between groups according to the two data sets of observed and expected response scores.</p> <p>Results</p> <p>We found that (1) it is necessary to report CIs for reliability and skewness coefficients in papers; (2) data derived from expected response scores are preferable to making inferences; and (3) visual representations displaying the 95% CIs of skewness values applied to item-by-item analyses can provide a useful interpretation of quality-of-life outcomes.</p> <p>Conclusion</p> <p>Reliability coefficients can be reported with 95% CIs by statistical software to evaluate the internal consistency of respondent scores on questionnaire items. The SPSS syntax procedures for estimating the reliability of the 95% CI, expected score generation and visual skewness analyses are demonstrated in this study. We recommend that effect sizes such as a 95% CI be reported along with <it>p </it>values reporting significant differences in quality-of-life studies.</p

    JNK suppression is essential for 17β-Estradiol inhibits prostaglandin E2-Induced uPA and MMP-9 expressions and cell migration in human LoVo colon cancer cells

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    <p>Abstract</p> <p>Background</p> <p>Epidemiological studies demonstrate that the incidence and mortality rates of colorectal cancer in women are lower than in men. However, it is unknown if 17β-estradiol treatment is sufficient to inhibit prostaglandin E2 (PGE2)-induced cellular motility in human colon cancer cells.</p> <p>Methods</p> <p>We analyzed the protein expression of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), matrix metallopeptidases (MMPs), plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteinases (TIMPs), and the cellular motility in PGE2-stimulated human LoVo cells. 17β-Estradiol and the inhibitors including LY294002 (Akt activation inhibitor), U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), QNZ (NFκB inhibitor) and ICI 182 780 were further used to explore the inhibitory effects of 17β-estradiol on PGE2-induced LoVo cell motility. Student's t-test was used to analyze the difference between the two groups.</p> <p>Results</p> <p>Upregulation of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) and matrix metallopeptidases (MMPs) is reported to associate with the development of cancer cell mobility, metastasis, and subsequent malignant tumor. After administration of inhibitors including LY294002, U0126, SB203580, SP600125 or QNZ, we found that PGE2 treatment up-regulated uPA and MMP-9 expression via JNK1/2 signaling pathway, thus promoting cellular motility in human LoVo cancer cells. However, PGE2 treatment showed no effects on regulating expression of tPA, MMP-2, plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinase-1, -2, -3 and -4 (TIMP-1, -2, -3 and -4). We further observed that 17β-estradiol treatment inhibited PGE2-induced uPA, MMP-9 and cellular motility by suppressing activation of JNK1/2 in human LoVo cancer cells.</p> <p>Conclusions</p> <p>Collectively, these results suggest that 17β-estradiol treatment significantly inhibits PGE2-induced motility of human LoVo colon cancer cells.</p

    Ultrasound-assisted degradation of a new bacterial exopolysaccharide WL-26 from Sphingomonas sp.

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    Ultrasonic degradation of a new exopolysaccharide WL-26 from Sphingomonas sp. was made over the frequency range 200 to 1200 Hz and polymer concentrations of 3, 5, 10 and 20 g/L using high performance anion exchange pulsed-amperometric detection chromatography (HPAEC–PAD) and infrared spectroscopy. Sonication was more efficient with less concentrated polysaccharide solutions, high ultrasonic frequency, long duration of ultrasonic irradiation and degradation continued until a limiting molecular weight was attained. Results show that HPAEC–PAD revealed WL-26 to be an acidic polysaccharide composed of rhamnose, glucose, mannose, galactose and glucuronic acid in the molar ratio of 10:9:3:1:3 distinctly different from welan gum which does not contain galactose.Key words: Exopolysaccharide WL-26, ultrasonic degradation, infrared spectroscopy
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