The Effect of Lexicality, Frequency, and Markedness on Mandarin Tonal Categorization

While the Ganong lexicality effect has been observed for phonemic and tonal categorization, the effects of frequency and markedness are less clear, especially in terms of tonal categorization. In this study, we use Mandarin Chinese to investigate the effects of lexicality, tone frequency and markedness. We examined Mandarin speakers’ tonal categorization of tokens on all possible tonal continua with one end being a word and the other being a tonotactic gap (i.e., an unattested syllable-tone combination). The results of a forced-choice identification experiment showed a general bias against the gap endpoints, with the noted exception of continua involving T4 (X51), the most frequent lexical tone. Specifically, when T4 served as the gap endpoint, no obvious bias against it was observed regardless of its lexical status. Moreover, on the T3–T4 continua, there was an apparent bias against T3 (X214), the tone with the most complex contour, again, regardless of lexicality, suggesting a strong markedness effect. Taken together, the results of this study show the individual effects of lexicality, tone frequency and markedness, as well as their interactions, which contribute to our understanding of tonal categorization in relation to lexical statistics (tone frequency) and phonology (markedness)

Paxillin facilitates timely neurite initiation on soft-substrate environments by interacting with the endocytic machinery.

Neurite initiation is the first step in neuronal development and occurs spontaneously in soft tissue environments. Although the mechanisms regulating the morphology of migratory cells on rigid substrates in cell culture are widely known, how soft environments modulate neurite initiation remains elusive. Using hydrogel cultures, pharmacologic inhibition, and genetic approaches, we reveal that paxillin-linked endocytosis and adhesion are components of a bistable switch controlling neurite initiation in a substrate modulus-dependent manner. On soft substrates, most paxillin binds to endocytic factors and facilitates vesicle invagination, elevating neuritogenic Rac1 activity and expression of genes encoding the endocytic machinery. By contrast, on rigid substrates, cells develop extensive adhesions, increase RhoA activity and sequester paxillin from the endocytic machinery, thereby delaying neurite initiation. Our results highlight paxillin as a core molecule in substrate modulus-controlled morphogenesis and define a mechanism whereby neuronal cells respond to environments exhibiting varying mechanical properties

Earthquake Probability Assessment for the Active Faults in Central Taiwan: A Case Study

Frequent high seismic activities occur in Taiwan due to fast plate motions. According to the historical records the most destructive earthquakes in Taiwan were caused mainly by inland active faults. The Central Geological Survey (CGS) of Taiwan has published active fault maps in Taiwan since 1998. There are 33 active faults noted in the 2012 active fault map. After the Chi-Chi earthquake, CGS launched a series of projects to investigate the details to better understand each active fault in Taiwan. This article collected this data to develop active fault parameters and referred to certain experiences from Japan and the United States to establish a methodology for earthquake probability assessment via active faults. We consider the active faults in Central Taiwan as a good example to present the earthquake probability assessment process and results. The appropriate “probability model” was used to estimate the conditional probability where M ≥ 6.5 and M ≥ 7.0 earthquakes. Our result shows that the highest earthquake probability for M ≥ 6.5 earthquake occurring in 30, 50, and 100 years in Central Taiwan is the Tachia-Changhua fault system. Conversely, the lowest earthquake probability is the Chelungpu fault. The goal of our research is to calculate the earthquake probability of the 33 active faults in Taiwan. The active fault parameters are important information that can be applied in the following seismic hazard analysis and seismic simulation

Dramatic Co-Activation of WWOX/WOX1 with CREB and NF-κB in Delayed Loss of Small Dorsal Root Ganglion Neurons upon Sciatic Nerve Transection in Rats

BACKGROUND:Tumor suppressor WOX1 (also named WWOX or FOR) is known to participate in neuronal apoptosis in vivo. Here, we investigated the functional role of WOX1 and transcription factors in the delayed loss of axotomized neurons in dorsal root ganglia (DRG) in rats. METHODOLOGY/PRINCIPAL FINDINGS:Sciatic nerve transection in rats rapidly induced JNK1 activation and upregulation of mRNA and protein expression of WOX1 in the injured DRG neurons in 30 min. Accumulation of p-WOX1, p-JNK1, p-CREB, p-c-Jun, NF-kappaB and ATF3 in the nuclei of injured neurons took place within hours or the first week of injury. At the second month, dramatic nuclear accumulation of WOX1 with CREB (>65% neurons) and NF-kappaB (40-65%) occurred essentially in small DRG neurons, followed by apoptosis at later months. WOX1 physically interacted with CREB most strongly in the nuclei as determined by FRET analysis. Immunoelectron microscopy revealed the complex formation of p-WOX1 with p-CREB and p-c-Jun in vivo. WOX1 blocked the prosurvival CREB-, CRE-, and AP-1-mediated promoter activation in vitro. In contrast, WOX1 enhanced promoter activation governed by c-Jun, Elk-1 and NF-kappaB. WOX1 directly activated NF-kappaB-regulated promoter via its WW domains. Smad4 and p53 were not involved in the delayed loss of small DRG neurons. CONCLUSIONS/SIGNIFICANCE:Rapid activation of JNK1 and WOX1 during the acute phase of injury is critical in determining neuronal survival or death, as both proteins functionally antagonize. In the chronic phase, concurrent activation of WOX1, CREB, and NF-kappaB occurs in small neurons just prior to apoptosis. Likely in vivo interactions are: 1) WOX1 inhibits the neuroprotective CREB, which leads to eventual neuronal death, and 2) WOX1 enhances NF-kappaB promoter activation (which turns to be proapoptotic). Evidently, WOX1 is the potential target for drug intervention in mitigating symptoms associated with neuronal injury

Anticancer drugs for the modulation of endoplasmic reticulum stress and oxidative stress

Prior research has demonstrated how the endoplasmic reticulum (ER) functions as a multifunctional organelle and as a well-orchestrated protein-folding unit. It consists of sensors which detect stress-induced unfolded/misfolded proteins and it is the place where protein folding is catalyzed with chaperones. During this folding process, an immaculate disulfide bond formation requires an oxidized environment provided by the ER. Protein folding and the generation of reactive oxygen species (ROS) as a protein oxidative byproduct in ER are crosslinked. An ER stress-induced response also mediates the expression of the apoptosis-associated gene C/EBP-homologous protein (CHOP) and death receptor 5 (DR5). ER stress induces the upregulation of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor and opening new horizons for therapeutic research. These findings can be used to maximize TRAIL-induced apoptosis in xenografted mice. This review summarizes the current understanding of the interplay between ER stress and ROS. We also discuss how damage-associated molecular patterns (DAMPs) function as modulators of immunogenic cell death and how natural products and drugs have shown potential in regulating ER stress and ROS in different cancer cell lines. Drugs as inducers and inhibitors of ROS modulation may respectively exert inducible and inhibitory effects on ER stress and unfolded protein response (UPR). Reconceptualization of the molecular crosstalk among ROS modulating effectors, ER stress, and DAMPs will lead to advances in anticancer therapy

Prediction of overall survival for patients with metastatic castration-resistant prostate cancer : development of a prognostic model through a crowdsourced challenge with open clinical trial data

Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0.791; Bayes factor >5) and surpassed the reference model (iAUC 0.743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3.32, 95% CI 2.39-4.62, p Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer.Peer reviewe

The Effects of Colors on the Shopping Appetence from Website: A Case Study on Yahoo Clothing Web

[[abstract]]With the high development of information technology and internet, shopping at website has already become one kind of new fashion trends. Shopping at internet is mainly through websites, so the user interface of webpage is the first impression that influences shopper’s feeling, which may affect the shopping appetence. Therefore, this research addresses the problem regarding the effects of interface color design on the users’ shopping appetence from the viewpoints of color psychology and visual communication. Improvement disposition, color disposition and whole disposition are adopted as the starting points to discuss what kind of color design will promote the users’ shopping appetence. The “Yahoo Clothing Website” is taken as the experimental object. A simulated modified interface is designed to illustrate the effectiveness of the new interface. The evaluation shows that the simulated interface with new color-design promote the users’ shopping appetence significantly. Finally, some color design principles for promoting users’ shopping appetence are also proposed. It is expected that the“Yahoo Clothing Website” or other shopping website could be benefited from using the suggested color design principles in their websits

Xanthomonas campestris pv. campestris 對線狀噬菌體 phiLf 敏感性之研究

Filamentous phage φLf specifically infects Xanthomonas campestris pv. campestris (Xcc). It has a single-stranded circular DNA with a genome site of 6,008 nucleotides. The φLf viral strand encodes nine genes organized into the order of gII-gX-gV-gVII-gIX-gVIII- gIII-gVI-gI, with gII, gX and gV shown to be required for replication, gVII, gIX, gVIII, gIII, and gVI encoding coat proteins, and gI responsible for assembly and morphogenesis. φLf-homologous region (fhr) is present on the chromosome of Xcc strain Xc17, next to the dif (deletion induced filamentation) site that is the end of chromosome replication. This region has been shown to site specific integration between dif site (attB) and the dif-homologous attP site in φLf, and homologous recombination via the fhr region outside dif. φLf can infect Xcc strain P20H, but can't infect Xc17. Xc17fhrΔ8361 was constructed from Xc17 containing gVIII, gIII, gVI and gI of fhr region replaced by Gmr cartridge.φLf can infect Xc17fhrΔ8361. The purpose of this study was to understand why φLf can't infect Xc17 ? Two experimental strategies were used for study: (I) Xc17 mutants with Gmr cartridge replaced the gVIII,gIII,gVI or gI gene in the fhr region were contracted and infected by φLf. (II) Xc17fhrΔ8361 transformants complemented with DNA fragments carrying Xc17fhr gVIII,gIII,gVI and gI were obtained and infected by φLf. Results showed that mutation of gVIII,gIII,gVI or gI gene in the fhr region of Xc17 causes no effects on φLf infection. Adsorption test results appeared that Xc17 mutants is no significant difference by φLf. Therefore, mutation in the gVIII~gIII, gVIII~gVI,gVIII~gI and gVIII~gI gene of Xc17 causes no effects on φLf infection. PCR amplification analysis results, showed that fhr region is absent in the genome of Xc17fhrΔ8361 and P20H. Based on the results, φLf infection isn't associated with gVIII,gIII,gVI,gI gene but pilA1. Expression levels of pilA1 are various among Xc17, Xc17fhrΔ8361 and P20H by real-time PCR. Higher expression level of pilA1 in P20H, φLf can efficiency infect host, and lower expression level of pilA1 in Xc17fhrΔ8361, φLf also can efficiency infect host, but lower expression level of pilA1 in Xc17, φLf can't infect host. Based on the results, presumably there is other factor more influence than pilA1 efficiency when φLf infected host.φLf 是十字花科蔬菜黑腐病菌 Xanthomonas campestris pv. campestris (Xcc) 之線狀噬菌體，其基因體為單股環狀 DNA，包含 6,008 個核苷酸。φLf 的基因排列與 E. coli Ff 噬菌體相似，順序為 gII - gX - gV - gVII - gIX - gVIII - gIII - gVI - gI。gII、gX 和 gV 與 DNA 複製有關，gVII、gIX、gVIII、gIII 和 gVI 主導噬菌體之外套蛋白，而 gI 產物則負責噬菌體之裝配與釋放。Xcc strain 17 (簡稱 Xc17) 的染色體複製終點 dif (deletion induced filamentation) site，也是 attB site，鄰近於 φLf–homologous region (fhr) 的右邊界。φLf 上的 attP site (位於 gI 下游) 可與宿主上的 attB 接觸，進行 site-specific integration，而 dif site 外圍之 fhr 區域則可供作進行 homologous recombination。φLf 可感染 Xcc strain P20H，但無法感染 Xc17；然而，前人將 Xc17 染色體上 fhr 區域中包含 gVIII、gIII、gVI和gI 的 DNA 片段以 Gmr 取代後，突變株即可被 φLf 感染，此突變株被命名為 Xc17fhrΔ8361。本研究目的為了解 Xc17 無法被 φLf 感染的原因。使用實驗策略如下：以插入突變法分別破壞 Xc17 染色體上 fhr 區域中的 gVIII、gIII、gVI 和 gI 基因，以了解哪個基因產物與 φLf 之感染有關。以及將 gVIII、gIII、gVI 和 gI 基因分別構築於質體上，轉殖送入 Xc17fhrΔ8361 突變株中，測試 φLf 的釋放情形。目前發現 φLf 無法感染上述個別基因被破壞的 Xc17 突變株。吸附率測試結果發現，相較於 Xc17，φLf 對於這些突變株的吸附能力亦無明顯差異。將 gVIII、gIII、gVI 和 gI 基因分別構築於質體上，再轉殖送入 Xc17fhrΔ8361 突變株後，以 spot test 和 plaque assay 測試，發現 φLf 依然能感染轉殖株，且轉殖株與 Xc17fhrΔ8361 釋出的噬菌體 titer 並無明顯差異。又構築 gVIII~gVI、gVIII~gI (Xc17fhrΔ8361L-1，gVIII、gIII、gVI 和 gI 基因全部被 Gmr 取代) 和 gVIII~gI (Xc17fhrΔ8361L-2，gVIII、gIII、gVI 和 gI 基因被 Gmr 取代，gVIII 基因部分保留) 刪除之突變株，發現 φLf 依然無法感染這些突變株。在實驗過程中發現，Xc17fhrΔ8361 與 Xc11 的突變株 P20H 的 EPS 含量和移動能力相似。於是，進一步利用 PCR 增幅分析 Xc17fhrΔ8361 與 P20H 在 fhr 區域以及 dif1 與 dif2 之相似性，發現 Xc17fhrΔ8361 與 P20H 都不具有 fhr 區域。由以上實驗中得知前人構築的 Xc17fhrΔ8361 基因體圖譜似乎與預期的不同，且 φLf 能感染宿主之原因與 fhr 區域的 gVIII、gIII、gVI 和 gI 基因之存在與否無關。已知 pilA1 與 φLf 的感染有關，因此利用 real-time PCR 檢測 Xc17、Xc17fhrΔ8361 與 P20H 之 pilA1 RNA 表現量。結果顯示菌株中 pilA1 RNA 量高低與 φLf 感染率無絕對相關。推測除了 pilA1 外，尚有其它因子能影響 φLf 是否會感染宿主。摘要……………………………………………………………………………………i Abstract…………………………………………………………………………… … ii 目錄…………………………………………………………………………...………iii 縮寫字對照表…………………………………………………………………… …..v 前言……………………………………………………………………………………1 材料……………………………………………………………………………………7 一、 菌種、噬菌體及質體……………………………………………………..….…7 二、 藥品……………………………………………………………………………...7 三、 酵素……………………………………………………………………………...7 四、 引子……………………………………………………………………………...7 五、 抗生素使用濃度…………………………………………………………………8 六、 培養基…………………………………………………………………………...8 (一) 液體培養基……………………………………………………………………...8 (二) 固體培養基……………………………………………………………………...8 七、 試劑及緩衝溶液………………………………………………………………..8 (一) 抽取質體 DNA 劑………………………………………………...................8 (二) DNA 電泳試劑………………………………………………………………...9 方法…………………………………………………………………………………..10 一、 細菌之培養與保存…………………………………………..……………..…10 二、 線狀噬菌體 φLf 之增殖與保存………………………………………….….10 三、 小量質體 DNA 之抽取…………………………………………………....…11 四、 質體之選殖……………………….……………………………...……………12 五、 DNA 補齊反應 (Fill in reaction)………………………………………….…..13 六、 轉型作用 (transformation)………..…………….…………………………….14 七、 X.campestris 之電穿孔法 (Electroporation)………………………15 八、洋菜膠電泳分析 (agarose gel electrophoresis)….…………….15 九、質體快速篩檢法……..…………………………………………………………16 十、線狀噬菌體 φLf RF DNA 之抽取……………………………………...……..16 十一、線狀噬菌體效價 (titer) 之測定……………………..………………………16 十二、點測試 (spot test)………………………………………...……………….…..17 十三、Plaque assay…………………………………………………………….……..17 十四、生長曲線與存活率測定…………………………….………………….……..17 十五、噬菌體吸附測試………………..……………………………………….…….18 十六、胞外酵素測試………………………….……………………………………….…….18 十七、胞外多醣 (extracellular polysaccharides, EPS) 測試…………………….….19 十八、細胞總蛋白量測試……………………………………………………………19 十九、移動能力測試 (motility test)…………………………………………………20 二十、質體構築………………………………………………………………………20 二十一、細胞 RNA 萃取 (total RNA extraction)……………………………21 二十二、反轉錄聚合酶連鎖反應 (RT-PCR)……………………………………….22 結果……………………………………………………………………...………..….24 一、 fhr 區域是否會影響噬菌體之複製與釋放………………………………24 二、 探討 fhr 區域中影響 φLf 感染 Xc17 之基因…………………25 三、 Xc17fhr 刪除突變株和野生株之生長差異………………………………27 四、 噬菌體 φLf 對不同菌株之吸附情形…………………………………...27 五、 噬菌體 φLf 感染 Xc17 和 Xc17 的 fhr 刪除突變株，並加入 mitomycin C (MMC)誘導後之差異…………………………........27 六、 噬菌體 φL7 感染 Xc17 和 Xc17fhrΔ8361 後生長與存活率之差異..........28 七、 Xc17、Xc17fhrΔ8361 和 P20H 胞外酵素分析…………………28 八、 Xc17、Xc17fhrΔ8361 和 P20H 產生 EPS 之分析…………29 九、 Xc17、Xc17fhrΔ8361、P20H 和 P20HpilA1::Gm 之 swarming 測試………30 十、 Xc17fhrΔ8361 的 fhr 區域分析……………………………………………...30 十一、依據前人構築 Xc17fhrΔ8361 的策略，重新獲得 Xc17fhrΔ8361L-2 突株，並觀察 φLf 感染此突變株之能力…………………32 十二、Xc17、Xc17fhrΔ8361 和 P20H 之 pilA1 RNA 表現差異…………………33 討論…………………………………………………………………………………..34 參考文獻……………………………………………………………………………..36 圖表…………………………………………………………………………………..4