Inhibition of c-Jun NH2-terminal kinase stimulates mu opioid receptor expression via p38 MAPK-mediated nuclear NF-κB activation in neuronal and non-neuronal cells

AbstractDespite its potential side effects of addiction, tolerance and withdrawal symptoms, morphine is widely used for reducing moderate and severe pain. Previous studies have shown that the analgesic effect of morphine depends on mu opioid receptor (MOR) expression levels, but the regulatory mechanism of MOR is not yet fully understood. Several in vivo and in vitro studies have shown that the c-Jun NH2-terminal kinase (JNK) pathway is closely associated with neuropathic hyperalgesia, which closely resembles the neuroplastic changes observed with morphine antinociceptive tolerance. In this study, we show that inhibition of JNK by SP600125, its inhibitory peptide, or JNK-1 siRNA induced MOR at both mRNA and protein levels in neuronal cells. This increase in MOR expression was reversed by inhibition of the p38 mitogen-activated protein kinase (MAPK) pathway, but not by inhibition of the mitogen-activated protein/extracellular signal-regulated kinase (MEK) pathway. Further experiments using cell signaling inhibitors showed that MOR upregulation by JNK inhibition involved nuclear factor-kappa B (NF-κB). The p38 MAPK dependent phosphorylation of p65 NF-κB subunit in the nucleus was increased by SP600125 treatment. We also observed by chromatin immunoprecipitation (ChIP) analysis that JNK inhibition led to increased bindings of CBP and histone-3 dimethyl K4, and decreased bindings of HDAC-2, MeCP2, and histone-3 trimethyl K9 to the MOR promoter indicating a transcriptional regulation of MOR by JNK inhibition. All these results suggest a regulatory role of the p38 MAPK and NF-κB pathways in MOR gene expression and aid to our better understanding of the MOR gene regulation

A full vectorial model for pulse propagation in emerging waveguides with subwavelength structures part II: Stimulated Raman Scattering

The significance of full vectorial pulse propagation through emerging waveguides has not been investigated. Here we report the development of a generalised vectorial model of nonlinear pulse propagation due to the effects of Stimulated Raman Scattering (SRS) in optical waveguides. Unlike standard models, this model does not use the weak guidance approximation, and thus accurately models the modal Raman gain of optical waveguides in the strong guidance regime. Here we develop a vectorial-based nonlinear Schrödinger Eq. (VNSE) to demonstrate how the standard model fails in certain regimes, with up to factors of 2.5 enhancement in Raman gain between the VNSE and the standard model. Using the VNSE we are able to explore opportunities for tailoring of the modal Raman gain spectrum to achieve effects such as gain flattening through design of the optical fiber.Mark D. Turner, Tanya M. Monro, and Shahraam Afshar V

The extreme European summer 2012

The European summer of 2012 was marked by strongly contrasting rainfall anomalies, which led to flooding in northern Europe and droughts and wildfires in southern Europe. This season was not an isolated event, rather the latest in a string of summers characterized by a southward shifted Atlantic storm track as described by the negative phase of the SNAO. The degree of decadal variability in these features suggests a role for forcing from outside the dynamical atmosphere, and preliminary numerical experiments suggest that the global SST and low Arctic sea ice extent anomalies are likely to have played a role and that warm North Atlantic SSTs were a particular contributing factor. The direct effects of changes in radiative forcing from greenhouse gas and aerosol forcing are not included in these experiments, but both anthropogenic forcing and natural variability may have influenced the SST and sea ice changes

Attribution of 2012 extreme climate events: does air-sea interaction matter?

In 2012, extreme anomalous climate conditions occurred around the globe. Large areas of North America experienced an anomalously hot summer, with large precipitation deficits inducing severe drought. Over Europe, the summer of 2012 was marked by strong precipitation anomalies with the UK experiencing its wettest summer since 1912 while Spain suffered severe drought. What caused these extreme climate conditions in various regions in 2012? This study compares attribution conclusions for 2012 climate anomalies relative to a baseline period (1964–1981) based on two sets of parallel experiments with different model configurations (with coupling to an ocean mixed layer model or with prescribed sea surface temperatures) to assess whether attribution conclusions concerning the climate anomalies in 2012 are sensitive to the representation of air-sea interaction. Modelling results indicate that attribution conclusions for large scale surface air temperature (SAT) changes in both boreal winter and summer are generally robust and not very sensitive to air-sea interaction. This is especially true over southern Europe, Eurasia, North America, South America, and North Africa. Some other responses also appear to be insensitive to air-sea interaction: for example, forced increases in precipitation over northern Europe and Sahel, and reduced precipitation over North America and the Amazon in boreal summer. However, the attribution of circulation and precipitation changes for some other regions exhibits a sensitivity to air-sea interaction. Results from the experiments including coupling to an ocean mixed layer model show a positive NAO-like circulation response in the Atlantic sector in boreal winter and weak changes in the East Asian summer monsoon and precipitation over East Asia. With prescribed sea surface temperatures, some different responses arise over these two regions. Comparison with observed changes indicates that the coupled simulations generally agree better with observations, demonstrating that attribution methods based on atmospheric general circulation models have limitations and may lead to erroneous attribution conclusions for regional anomalies in circulation, precipitation and surface air temperature

Calibration of the 14C time scale to >40 ka by 234U–230Th dating of Lake Lisan sediments (last glacial Dead Sea)

A new comparison of 14C dates with 234U-230Th ages is presented of aragonites from Lake Lisan, the last Glacial Dead Sea, between ∼20–52 cal-ka-BP. The Lisan data are coincident with the coral based 14C-calendar age calibration through the continuous portion of the curve to 23.5 cal-ka-BP, and with the additional ‘checkpoints’ at ∼30 and ∼40 cal-ka-BP. The agreement with the corals provides evidence for the accuracy of the U-Th and 14C ages, and indicates that Lisan aragonites can potentially be used to generate a nearly continuous record of the atmospheric 14C variations through this crucial time interval. The Lisan data are compared with other records older than 25 cal-ka-BP from Lake Suigetsu, Japan, North Atlantic foraminifera, South African cave deposits and tufa from Spain. Over some age intervals the records show broad agreement, over other intervals they diverge. All agree that 14C ages were ∼2.5±0.5 ka younger than calendar ages between 20–32 cal-ka-BP. For ages >32 cal-ka-BP, the Lake Suigetsu data indicate small differences between 14C ages and calendar ages of less than 1.5 ka. The other records broadly agree that 14C ages are too young by ∼3±1 ka from 32–39 cal-ka-BP. At ∼40 cal-ka-BP, the foraminifera show equal 14C and calendar ages, while the corals, Lisan aragonites and the Spanish tufa indicate a large age difference of 4–5 ka. A recent paleomagnetic study of the Lisan Formation indicates that the high calendar-14C age difference at ∼40 cal-ka-BP may be associated with the Laschamp paleomagnetic excursion

Explaining Extreme Events of 2012 from a Climate Perspective

Attribution of extreme events is a challenging science and one that is currently undergoing considerable evolution. In this paper are 19 analyses by 18 different research groups, often using quite different methodologies, of 12 extreme events that occurred in 2012. In addition to investigating the causes of these extreme events, the multiple analyses of four of the events, the high temperatures in the United States, the record low levels of Arctic sea ice, and the heavy rain in northern Europe and eastern Australia, provide an opportunity to compare and contrast the strengths and weaknesses of the various methodologies. The differences also provide insights into the structural uncertainty of event attribution, that is, the uncertainty that arises directly from the differences in analysis methodology. In these cases, there was considerable agreement between the different assessments of the same event. However, different events had very different causes. Approximately half the analyses found some evidence that anthropogenically caused climate change was a contributing factor to the extreme event examined, though the effects of natural fluctuations of weather and climate on the evolution of many of the extreme events played key roles as well.Peer Reviewe

連續滯洪池滯洪效應之研究

在坡地開發中所需設置的滯洪池因經濟成本以及土地利用等因素可以單一式滯洪池以及連續式滯洪池來因應。 本研究初步建立單一式滯洪池與連續式滯洪池之水文分析理論，同時配合渠槽試驗。將單一式滯洪池與連續式滯洪池之入流量及出流量固定，來探討滯洪體積、體積比值與稽延時間等變因之變化關係。 結果發現連續式滯洪池之滯洪體積比單一式來的大，渠槽坡度較陡，則滯洪體積大的比例會小一些。另外，在坡度較陡的區域設置連續式滯洪池，其安全性將優於在同一區域設置單一式滯洪池。體積比值當中，當上池出流量 O1=(I1*O1)^0.5 時，最大滯洪體積之比例為5：5。在相同之洪峰削減量下，連續式滯洪池洪峰稽延時間比單一式滯洪池長。The detention ponds, which are required in the development of the slopeland, can be divided into single flood detention pond and consecutive flood detention ponds by the reasons of cost and land use. In this study, we establish the hydrology theory for the single flood detention pond and the consecutive flood detention ponds. We also made a flume experiment. We compared detention volume with the single flood detention pond and the consecutive flood detention ponds. Also, with the same outflow and inflow, we discussed the detention effect for different flume slope and proportion of detention volume. In the result, we found out that for the same detention effect, the volume of the consecutive flood detention ponds is larger than the single flood detention pond. The excessive detention volume rate will decrease while the flume slope increases. In addition, it will be safer to construct consecutive detention ponds at steeper land than to construct single flood detention. With the ratio of volume, When a outflow of the up pond, equals to another, , the proportion of the greatest volume of the flood detention ponds is 5:5.With the same peak attenuation, consecutive flood pond is longer than the single flood in the variation of peak lags.目錄 一.前言---------------------------------------------------1 1.1研究緣起-----------------------------------------------1 1.2研究動機-----------------------------------------------1 1.3研究目的-----------------------------------------------2 二.前人研究-----------------------------------------------3 2.1滯洪設施之相關研究-------------------------------------3 2.2滯洪體積之相關研究-------------------------------------6 2.3洪峰稽延之相關研究-------------------------------------8 2.4流量公式之相關研究-------------------------------------8 三.理論分析----------------------------------------------13 3.1理論方法----------------------------------------------13 3.2理論公式----------------------------------------------23 四.室內試驗設計------------------------------------------25 4.1試驗設備----------------------------------------------25 4.2試驗步驟----------------------------------------------31 五.結果分析與討論----------------------------------------38 5.1定量流試驗結果分析------------------------------------38 5.2變量流試驗結果分析------------------------------------44 5.3討論--------------------------------------------------61 六.結論與建議--------------------------------------------63 6.1結論--------------------------------------------------63 6.2建議--------------------------------------------------64 參考文獻-------------------------------------------------65 附錄一. 實驗數據------------------------------------附錄1-0 附錄二..流量歴線圖----------------------------------附錄2-0 圖目錄 圖3-1 單一式滯洪池歴線示意圖-----------------------------14 圖3-2 連續式滯洪池歴線示意圖-----------------------------15 圖3-3 單一式滯洪池歴線示意圖-----------------------------16 圖3-4 連續式滯洪池歴線示意圖-----------------------------17 圖3-5 單一式滯洪池洪峰稽延示意圖-------------------------21 圖3-6 連續式滯洪池洪峰稽延示意圖-------------------------22 圖4-1 三角堰設計示意圖-----------------------------------25 圖4-2 壓克力三角堰示意圖---------------------------------26 圖4-3 固定式開口滯洪壩模型正視圖-------------------------26 圖4-4 試驗渠槽平面配置與側視圖---------------------------27 圖4-5 試驗渠槽上下游照片---------------------------------27 圖4-6 抽水幫浦照片---------------------------------------28 圖4-7 水桶照片-------------------------------------------28 圖4-8 吸水海綿照片---------------------------------------28 圖4-9 活動式開口滯洪壩照片-------------------------------29 圖4-10 固定式開口滯洪壩照片------------------------------29 圖4-11 位移測針平台照片----------------------------------29 圖4-12 三角堰照片----------------------------------------30 圖4-13 調整用方塊照片------------------------------------30 圖4-14 單一式滯洪池側面示意圖----------------------------32 圖4-15 連續式滯洪池側面示意圖----------------------------33 圖4-16 連續式滯洪池上下池體積6：4側面示意圖--------------33 圖4-17 連續式滯洪池上下池體積4：6側面示意圖--------------33 圖4-18 三角堰入流照片------------------------------------34 圖4-19 單一式滯洪池照片----------------------------------35 圖4-20 方塊調整體積前照片--------------------------------35 圖4-21 方塊調整體積後照片--------------------------------35 圖5-1 以吸管構成之整流裝置示意圖-------------------------38 圖5-2 流量與有效水深之關係圖-----------------------------39 圖5-3 不同配置之三種坡度下滯洪體積與流量之關係圖---------49 圖5-4 相同配置之三種坡度下滯洪體積與流量之關係圖---------50 圖5-5 上池之尖峰出流量與滯洪體積比值之關係圖-------------51 圖5-6 流量與稽延時間之關係圖-----------------------------59 圖5-7 連續式滯洪池在坡度較陡地區-------------------------62 表目錄 表5-1 流量係數數據表-------------------------------------39 表5-2 方塊體積ㄧ覽表-------------------------------------41 表5-3 單一池試驗數據整理---------------------------------44 表5-4 連續池坡度ㄧ度時試驗數據整理-----------------------45 表5-5 連續池坡度三度時試驗數據整理-----------------------46 表5-6 連續池坡度五度時試驗數據整理-----------------------47 表5-7 上池洪峰出流量與Sr比值一覽表-----------------------52 表5-8 體積比值Sr與上、下池比例Sa/Sb 一覽表---------------57 表5-9 各配置之稽延時間一覽表-----------------------------5