Acarbose: A New Option in the Treatment of Ulcerative Colitis by Increasing Hydrogen Production

Acarbose，which is clinically widely used to treat Type 2 Diabetes，is thought to act at the small intestine by competitively inhibiting enzymes that delay the release of glucose from complex carbohydrates, thereby specifically reducing post prandial glucose excursion. The major side-effect of treatment with acarbose, flatulence, occurs when undigested carbohydrates are fermented by colonic bacteria, resulting in considerable amount of hydrogen. We propose that enteric benefits of acarbose is partly attributable to be their ability to neutralise oxidative stress via increased production of H2 in the gastrointestinal tract. Therefore, symptoms of ulcerative colitis in human beings can be ameliorated by acarbose

Broadband gradient impedance matching using an acoustic metamaterial for ultrasonic transducers

2016-2017 > Academic research: refereed > Publication in refereed journal201804_a bcmaVersion of RecordPublishe

Wide Area Measuring System Signals Based Nonlinear Robust Adaptive DC Power Modulation Controller in AC/DC Interconnected Power System

The robust adaptive control law is proposed for a HVDC power modulation controller of the interconnected AC/DC power system. Based on the design idea of driving the center of inertia (COI) of different areas to a stable equilibrium point, the proposed controller is applied to damp inter-area oscillation of interconnected AC/ DC system using global signals of a wide area measuring system (WAMS). Designed by the back-stepping method, the robust adaptive control law is adaptive to the unknown parameters and is robust to model error, disturbances and different equilibrium points. Computer results show that the controller proposed is obviously superior to the conventional DC power modulation controller in damping inter-area oscillation and enhancing the power transfer limit. In addition, its performance can well adapt to the change of the equilibrium point. 設計了應用于交直流互聯電力系統的直流功率調制的非線性魯棒自適應控制器。該控制器基于驅動各互聯區域電網的慣量中心至統一平衡點的設計思想,采用廣域測量系統的全局信號,用以阻尼交直流互聯系統的區域間功率振蕩。采用反步法設計的自適應魯棒控制規律使控制器對未知參數具有自適應性,對模型誤差、擾動和平衡點變化具有較強的魯棒性。仿真結果表明,與傳統的線性直流功率調制控制器相比,該控制器對聯絡線的功率振蕩具有優良的阻尼性能,可顯著提高輸電極限,而且能很好地適應運行點的變化。link_to_OA_fulltex

Three geographically separate domestications of Asian rice

Domesticated rice (Oryza sativa L.) accompanied the dawn of Asian civilization(1) and has become one of world's staple crops. From archaeological and genetic evidence various contradictory scenarios for the origin of different varieties of cultivated rice have been proposed, the most recent based on a single domestication(2,3). By examining the footprints of selection in the genomes of different cultivated rice types, we show that there were three independent domestications in different parts of Asia. We identify wild populations in southern China and the Yangtze valley as the source of the japonica gene pool, and populations in Indochina and the Brahmaputra valley as the source of the indica gene pool. We reveal a hitherto unrecognized origin for the aus variety in central India or Bangladesh. We also conclude that aromatic rice is a result of a hybridization between japonica and aus, and that the tropical and temperate versions of japonica are later adaptations of one crop. Our conclusions are in accord with archaeological evidence that suggests widespread origins of rice cultivation(1,4). We therefore anticipate that our results will stimulate a more productive collaboration between genetic and archaeological studies of rice domestication, and guide utilization of genetic resources in breeding programmes aimed at crop improvement.European Research Council [339941]info:eu-repo/semantics/publishedVersio

Cancer genomics and biology 2015 - Meeting report

published_or_final_versio

Theories of behaviour change synthesised into a set of theoretical groupings: Introducing a thematic series on the Theoretical Domains Framework

Behaviour change is key to increasing the uptake of evidence into healthcare practice. Designing behaviour-change interventions first requires problem analysis, ideally informed by theory. Yet the large number of partly overlapping theories of behaviour makes it difficult to select the most appropriate theory. The need for an overarching theoretical framework of behaviour change was addressed in research in which 128 explanatory constructs from 33 theories of behaviour were identified and grouped. The resulting Theoretical Domains Framework (TDF) appears to be a helpful basis for investigating implementation problems. Research groups in several countries have conducted TDF-based studies. It seems timely to bring together the experience of these teams in a thematic series to demonstrate further applications and to report key developments. This overview article describes the TDF, provides a brief critique of the framework, and introduces this thematic series. In a brief review to assess the extent of TDF-based research, we identified 133 papers that cite the framework. Of these, 17 used the TDF as the basis for empirical studies to explore health professionals’ behaviour. The identified papers provide evidence of the impact of the TDF on implementation research. Two major strengths of the framework are its theoretical coverage and its capacity to elicit beliefs that could signify key mediators of behaviour change. The TDF provides a useful conceptual basis for assessing implementation problems, designing interventions to enhance healthcare practice, and understanding behaviour-change processes. We discuss limitations and research challenges and introduce papers in this series

Radiotherapy-induced cell death activates paracrine HMGB1-TLR2 signaling and accelerates pancreatic carcinoma metastasis

Background: Dying cells after irradiation could promote the repopulation of surviving cancer cells leading to tumor recurrence. We aim to define the role of dying cells in promoting pancreatic cancer cells metastasis following radiotherapy.Methods: Using the transwell system as the in vitro co-culture model, a small number of untreated pancreatic cancer cells were seeded in the upper chamber, while a larger number of lethally treated pancreatic cancer cells were seeded in the lower chamber. A series of experiments were conducted to investigate the role of dying-cell-derived HMGB1 on the invasion of pancreatic cancer in vitro and cancer metastasis in vivo. We then designed shRNA knockdown and Western blot assays to detect signaling activity.Results: We found that dying pancreatic cancer cells significantly promote the invasion of pancreatic cancer cells in vitro and cancer metastasis in vivo. HMGB1 gene knockdown attenuated the migration-stimulating effect of irradiated, dying cells on living pancreatic cancer cells. Finally, we showed that dying-cell-derived HMGB1 functions in a paracrine manner to affect cancer-cell migration dependent on acquiring an epithelial-mesenchymal transition (EMT) phenotype and PI3K/pAkt activation. This process is mediated by the receptor for TLR2.Conclusion: Our study indicates that, during radiotherapy, dying pancreatic cancer cells activate paracrine signaling events that promote the mobility of surviving tumor cells. We suggest a strategy to inhibit HMGB1 for preventing pancreatic carcinoma relapse and metastasis

Improved gradient descent algorithms for time-delay rational state-space systems: Intelligent search method and momentum method

This study proposes two improved gradient descent parameter estimation algorithms for rational state-space models with time-delay. These two algorithms, based on intelligent search method and momentum method, can simultaneously estimate the time-delay and parameters without the matrix eigenvalue calculation in each iteration. Compared with the traditional gradient descent algorithm, the improved algorithms come with two advantages: having quicker convergence rates and less computational efforts, particularly meaningful for those large scale systems. A simulated example is selected to illustrate the efficiency of the proposed algorithms

New Mouse Lines for the Analysis of Neuronal Morphology Using CreER(T)/loxP-Directed Sparse Labeling

BACKGROUND: Pharmacologic control of Cre-mediated recombination using tamoxifen-dependent activation of a Cre-estrogen receptor ligand binding domain fusion protein [CreER(T)] is widely used to modify and/or visualize cells in the mouse. METHODS AND FINDINGS: We describe here two new mouse lines, constructed by gene targeting to the Rosa26 locus to facilitate Cre-mediated cell modification. These lines should prove particularly useful in the context of sparse labeling experiments. The R26rtTACreER line provides ubiquitous expression of CreER under transcriptional control by the tetracycline reverse transactivator (rtTA); dual control by doxycycline and tamoxifen provides an extended dynamic range of Cre-mediated recombination activity. The R26IAP line provides high efficiency Cre-mediated activation of human placental alkaline phosphatase (hPLAP), complementing the widely used, but low efficiency, Z/AP line. By crossing with mouse lines that direct cell-type specific CreER expression, the R26IAP line has been used to produce atlases of labeled cholinergic and catecholaminergic neurons in the mouse brain. The R26IAP line has also been used to visualize the full morphologies of retinal dopaminergic amacrine cells, among the largest neurons in the mammalian retina. CONCLUSIONS: The two new mouse lines described here expand the repertoire of genetically engineered mice available for controlled in vivo recombination and cell labeling using the Cre-lox system

Branched-chain amino acid aminotransferase 2 regulates ferroptotic cell death in cancer cells

Ferroptosis, a form of iron-dependent cell death driven by cellular metabolism and iron-dependent lipid peroxidation, has been implicated as a tumor-suppressor function for cancer therapy. Recent advance revealed that the sensitivity to ferroptosis is tightly linked to numerous biological processes, including metabolism of amino acid and the biosynthesis of glutathione. Here, by using a high-throughput CRISPR/Cas9-based genetic screen in HepG2 hepatocellular carcinoma cells to search for metabolic proteins inhibiting ferroptosis, we identified a branched-chain amino acid aminotransferase 2 (BCAT2) as a novel suppressor of ferroptosis. Mechanistically, ferroptosis inducers (erastin, sorafenib, and sulfasalazine) activated AMPK/SREBP1 signaling pathway through iron-dependent ferritinophagy, which in turn inhibited BCAT2 transcription. We further confirmed that BCAT2 as the key enzyme mediating the metabolism of sulfur amino acid, regulated intracellular glutamate level, whose activation by ectopic expression specifically antagonize system Xc(-) inhibition and protected liver and pancreatic cancer cells from ferroptosis in vitro and in vivo. On the contrary, direct inhibition of BCAT2 by RNA interference, or indirect inhibition by blocking system Xc(-) activity, triggers ferroptosis. Finally, our results demonstrate the synergistic effect of sorafenib and sulfasalazine in downregulating BCAT2 expression and dictating ferroptotic death, where BCAT2 can also be used to predict the responsiveness of cancer cells to ferroptosis-inducing therapies. Collectively, these findings identify a novel role of BCAT2 in ferroptosis, suggesting a potential therapeutic strategy for overcoming sorafenib resistance