Remifentanil post-conditioning attenuates cardiac ischemia-reperfusion injury via κ or δ opioid receptor activation

Background: Ischemic pre- or post-conditioning of the heart has been shown to involve opioid receptors. Remifentanil, an ultra-short-acting selective μ opioid receptor agonist in clinical use, pre-conditions the rat heart against ischemia-reperfusion injury. This study investigates whether remifentanil post-conditioning is also cardioprotective. Methods: Remifentanil post-conditioning (5-min infusion at 1, 5, 10 or 20 μg/kg/min) or ischemic post-conditioning (three cycles of a 10 s reperfusion interspersed with a 10 s ischemia) was induced in an open-chest rat heart model of ischemia and reperfusion injury, in the presence or absence of nor-binaltorphimine, naltrindole or CTOP, specific κ, δ and μ opioid receptor antagonists, respectively. The same sequence of experiments was repeated in the isolated heart model using the maximal protective dose of remifentanil from the dose-response studies. Results: Both ischemic and remifentanil post-conditioning reduced the myocardial infarct size relative to the control group in both models. This cardioprotective effect for both post-conditioning regimes was prevented by the prior administration of nor-binaltorphimine and naltrindole but not CTOP. The sole administration of the antagonists had no effect on the size of myocardial infarction. Conclusions: These results indicate that remifentanil post-conditioning protects the heart from ischemia-reperfusion injury to a similar extent as of ischemic post-conditioning. This protection involves κ and δ but not μ opioid receptor activation. This drug has great potential as a clinical post-conditioning modality as it can be given in large doses without prolonged opioid-related side effects. © 2009 The Acta Anaesthesiologica Scandinavica Foundation.postprin

E2F1 Downregulation by Arsenic Trioxide in Lung Adenocarcinoma

Lung cancer is one of the most common cancers worldwide. Arsenic trioxide (ATO) has been approved by the U.S. Food and Drug Administration for the treatment of acute promyelocytic leukemia. Nonetheless preliminary data have suggested potential activity of ATO in solid tumors including lung cancer. This study aimed to examine the underlying mechanisms of ATO in the treatment of lung adenocarcinoma. Using a panel of 7 lung adenocarcinoma cell lines, the effects of ATO treatment on cell viability, expression of E2F1 and its downstream targets, phosphatidylserine externalization, mitochondrial membrane depolarization and alteration of apoptotic/anti-apoptotic factors were studied. Tumor growth inhibition in vivo was investigated using a nude mouse xenograft model. ATO decreased cell viability with clinically achievable concentrations (8 uM) in all cell lines investigated. This was accompanied by reduced expression of E2F1, cyclin A2, skp2, c-myc, thymidine kinase and ribonucleotide reductase M1, while p-c-Jun was upregulated. Cell viability was significantly decreased with E2F1 knockdown. Treatment with ATO resulted in phosphatidylserine externalization in H23 cells and mitochondrial membrane depolarization in all cell lines, associated with truncation of Bid, downregulation of Bcl-2, upregulation of Bax and Bak, caspase-9 and caspase-3 activation and PARP cleavage. Using a H358 xenograft model, the tumor growth was suppressed in the ATO treatment group during 8 days of treatment, associated with downregulation of E2F1 and upregulation of truncated Bid and cleaved caspase-3. In conclusion, ATO has potent in vitro and in vivo activity in lung adenocarcinoma, partially mediated through E2F1 downregulation and apoptosis.published_or_final_versio

Modelling the unfolding pathway of biomolecules: theoretical approach and experimental prospect

We analyse the unfolding pathway of biomolecules comprising several independent modules in pulling experiments. In a recently proposed model, a critical velocity $v_{c}$ has been predicted, such that for pulling speeds $v>v_{c}$ it is the module at the pulled end that opens first, whereas for $v<v_{c}$ it is the weakest. Here, we introduce a variant of the model that is closer to the experimental setup, and discuss the robustness of the emergence of the critical velocity and of its dependence on the model parameters. We also propose a possible experiment to test the theoretical predictions of the model, which seems feasible with state-of-art molecular engineering techniques.Comment: Accepted contribution for the Springer Book "Coupled Mathematical Models for Physical and Biological Nanoscale Systems and Their Applications" (proceedings of the BIRS CMM16 Workshop held in Banff, Canada, August 2016), 16 pages, 6 figure

Asymmetric hydroformylation of styrene catalyzed by pyranoside diphosphite-rh(Ⅰ) complexes

2006-2007 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

The ubiquitin ligase TRIM27 functions as a host restriction factor antagonized by Mycobacterium tuberculosis PtpA during mycobacterial infection

published_or_final_versio

The Influence of Accumulated Precipitation on Debris Flow Hazard

Debris flow warning system in Taiwan uses effective accumulated precipitation as the warning criteria. Little research has studied the affected area associated with different levels of accumulated precipitation. The Taipei DF024 potential debris flow torrent is used as an example to study the relation between an affected area and accumulated precipitation. Three different amount of accumulated precipitation 300, 500 (official warning criteria) and 700 mm in 24 hours are chosen for comparison. Average rainfall intensity per hour is calculated from accumulated rainfall through the Monobe formula. Total water flow rate is estimated using the Rational formula and a discharge hydrograph. Maximum debris flow volume is determined by the equilibrium concentration formula. All sources of debris are distributed on landslide areas and river bed from field investigation. DEBRIS-2D is used to simulate debris flows. The results show that the hazard area is proportional to precipitation, and the thickness of maximum debris flow accumulation is between 3 and 3.5 m for all three cases. The relation between accumulated precipitation and hazard area can provide officials with additional information related to resident evacuation.土石流預警在台灣是以有效累積雨量為基準，但在不同累積雨量下的土石流災害範圍，卻少有學者討論。針對這個問題，本文以北市DF024 為例，用其警戒雨量500 毫米做為基準，再選300 和700 毫米的累積雨量做影響範圍的比較。透過物部公式 (Monobe formula) 將累積雨量轉換為降雨強度，並搭配合理化公式和流量歷線去估算集水區產生的總水量，再以土石流平衡濃度公式推估土石流體積量。並經過現場調查，將料源分佈於崩坍地與河床崩積層，最後採用DEBRIS-2D 去模擬土石流影響範圍。在北市DF024 的案例中發現，土石流影響範圍會隨著累積雨量的增加而擴大，但最大土石堆積深度皆在3~3.5 公尺之間。透過此方法得到的土石流影響範圍不只可以連結與累積雨量的關係，並且可提供相關單位一個修正警戒雨量或疏散 範圍決策的參考

Inference of population splits and mixtures from genome-wide allele frequency data

Many aspects of the historical relationships between populations in a species are reflected in genetic data. Inferring these relationships from genetic data, however, remains a challenging task. In this paper, we present a statistical model for inferring the patterns of population splits and mixtures in multiple populations. In this model, the sampled populations in a species are related to their common ancestor through a graph of ancestral populations. Using genome-wide allele frequency data and a Gaussian approximation to genetic drift, we infer the structure of this graph. We applied this method to a set of 55 human populations and a set of 82 dog breeds and wild canids. In both species, we show that a simple bifurcating tree does not fully describe the data; in contrast, we infer many migration events. While some of the migration events that we find have been detected previously, many have not. For example, in the human data we infer that Cambodians trace approximately 16% of their ancestry to a population ancestral to other extant East Asian populations. In the dog data, we infer that both the boxer and basenji trace a considerable fraction of their ancestry (9% and 25%, respectively) to wolves subsequent to domestication, and that East Asian toy breeds (the Shih Tzu and the Pekingese) result from admixture between modern toy breeds and "ancient" Asian breeds. Software implementing the model described here, called TreeMix, is available at http://treemix.googlecode.comComment: 28 pages, 6 figures in main text. Attached supplement is 22 pages, 15 figures. This is an updated version of the preprint available at http://precedings.nature.com/documents/6956/version/

The radial dimension of a supersonic jet expansion from conical nozzle

In a laser-cluster interaction experiment, the radial dimension of a supersonic gas jet is an important parameter for the characterization of interaction volume. It is noted that due to the lateral gas expansion, the diameter of a supersonic gas jet is larger than the idealized diameter of a gas jet from a conical nozzle. In this work the effect of the lateral expansion on the radial dimension of gas jet was investigated by simulations. Based on the simulation results, the diameter of gas jet l was compared in detail with the corresponding diameter l(T) in the idealized straight streamline model and the diameter l(H) at a half of maximum atom density of gas jet. The results reveal how the deviation of l from l(T) (l(H)) changes with respect to the opening angles of conical nozzles, the heights above the nozzle, the nozzle lengths and the gas backing pressures. It is found that the diameter of gas jet l is close to the idealized diameter l(T) and l(H) in the case where a long conical nozzle with a large opening angle is used under a low gas backing pressure. In this case, the effect of the lateral expansion is so weak that the edge of gas jet becomes sharp and the radial distribution of atom density in gas jet tends to be uniform. The results could be useful for the characterization of a supersonic gas jet. (C) 2016 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).110Ysciescopu