bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of botulinum toxin A on vasoconstriction and sympathetic neurotransmitters in a murine random pattern skin flap model
Authors: Roh Tai Suk , Jung Bok Ki , Yun Insik , Lew Dae Hyun , Kim Young Seok 
Published: December 2016

AbstractBlood supply is the most important factor determining the survival of a skin flap. Botulinum toxin‐A (Botox‐A) is used as pharmacologic agent not only for aesthetic purposes, but also for its vasomotor actions. This study was conducted to establish whether local application of Botox‐A increased survival of random pattern skin flaps in rats by changing the expression of neurotransmitters. Forty adult Sprague–Dawley rats with a caudally‐based random pattern skin flap were divided into two groups: Botox‐A group and saline group. Surviving flap area and cutaneous blood flow in the flap were evaluated on postoperative days 3 and 7. After injection of Botox‐A, changes in vessels were analyzed using immunohistochemical staining. Levels of norepinephrine, neuropeptide‐Y, nitric oxide, and endothelial nitric oxide synthase were analyzed quantitatively by high performance liquid chromatography, Western blot, and colorimetric assay. The survived area in the Botox‐A group was significantly higher than that in the control group on postoperative days 3 and 7. Blood flow in the Botox‐A group was significantly high in the proximal and middle areas immediately after the operation. The number of CD31‐positive vessels in the Botox‐A group was significant greater than that in the control group. Norepinephrine level in the Botox‐A group decreased significantly immediately after flap elevation and at postoperative day 3. There were no significant differences in neuropeptide‐Y level between the two groups. Nitric oxide level did not change significantly in either group despite the increase in endothelial nitric oxide synthase immediately after flap elevation and at 3 days postoperatively. In conclusion, Botox‐A increased vascular blood flow and viable flap area in rats by reducing norepinephrine level. In contrast, neuropeptide‐Y, another vasoconstrictor, was not affected by Botox‐A. Nitric oxide, a vasodilator, was also not affected by Botox‐A, despite the significant increase in endothelial nitric oxide synthase expression in the flaps.
Bicarbonate‐rich fluid secretion predicted by a computational model of guinea‐pig pancreatic duct epithelium
Authors: Yamaguchi Makoto , Steward Martin C. , Smallbone Kieran , Sohma Yoshiro , Yamamoto Akiko , Ko Shigeru B. H. , Kondo Takaharu , Ishiguro Hiroshi 
Published: December 2016

Key points
The ductal system of the pancreas secretes large volumes of alkaline fluid containing HCO3− concentrations as high as 140 mm during hormonal stimulation.
A computational model has been constructed to explore the underlying ion transport mechanisms. Parameters were estimated by fitting the model to experimental data from guinea‐pig pancreatic ducts.
The model was readily able to secrete 140 mm HCO3−. Its capacity to do so was not dependent upon special properties of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channels and solute carrier family 26 member A6 (SLC26A6) anion exchangers.
We conclude that the main requirement for secreting high HCO3− concentrations is to minimize the secretion of Cl− ions.
These findings help to clarify the mechanism responsible for pancreatic HCO3− secretion, a vital process that prevents the formation of protein plugs and viscous mucus in the ducts, which could otherwise lead to pancreatic disease.
AbstractA computational model of guinea‐pig pancreatic duct epithelium was developed to determine the transport mechanism by which HCO3− ions are secreted at concentrations in excess of 140 mm. Parameters defining the contributions of the individual ion channels and transporters were estimated by least‐squares fitting of the model predictions to experimental data obtained from isolated ducts and intact pancreas under a range of experimental conditions. The effects of cAMP‐stimulated secretion were well replicated by increasing the activities of the basolateral Na+‐HCO3− cotransporter (NBC1) and apical Cl−/HCO3− exchanger (solute carrier family 26 member A6; SLC26A6), increasing the basolateral K+ permeability and apical Cl− and HCO3− permeabilities (CFTR), and reducing the activity of the basolateral Cl−/HCO3− exchanger (anion exchanger 2; AE2). Under these conditions, the model secreted ∼140 mm HCO3− at a rate of ∼3 nl min−1 mm−2, which is consistent with experimental observations. Alternative 1:2 and 1:1 stoichiometries for Cl−/HCO3− exchange via SLC26A6 at the apical membrane were able to support a HCO3−‐rich secretion. Raising the HCO3−/Cl− permeability ratio of CFTR from 0.4 to 1.0 had little impact upon either the secreted HCO3− concentration or the volume flow. However, modelling showed that a reduction in basolateral AE2 activity by ∼80% was essential in minimizing the intracellular Cl− concentration following cAMP stimulation and thereby maximizing the secreted HCO3− concentration. The addition of a basolateral Na+‐K+‐2Cl− cotransporter (NKCC1), assumed to be present in rat and mouse ducts, raised intracellular Cl− and resulted in a lower secreted HCO3− concentration, as is characteristic of those species. We conclude therefore that minimizing the driving force for Cl− secretion is the main requirement for secreting 140 mm HCO3−.
Plasma Circulating Tumor DNA in Pancreatic Cancer Patients Is a Prognostic Marker
Authors: Pietrasz Daniel , Pécuchet Nicolas , Garlan Fanny , Didelot Audrey , Dubreuil Olivier , Doat Solène , Imbert-Bismut Francoise , Karoui Mehdi , Vaillant Jean-Christophe , Taly Valérie , Laurent-Puig Pierre , Bachet Jean-Baptiste 
Published: December 2016

Abstract
Purpose: Despite recent therapeutic advances, prognosis of patients with pancreatic adenocarcinoma remains poor. Analyses from tumor tissues present limitations; identification of informative marker from blood might be a promising alternative. The aim of this study was to assess the feasibility and the prognostic value of circulating tumor DNA (ctDNA) in pancreatic adenocarcinoma.
Experimental Design: From 2011 to 2015, blood samples were prospectively collected from all consecutive patients with pancreatic adenocarcinoma treated in our center. Identification of ctDNA was done with next-generation sequencing targeted on referenced mutations in pancreatic adenocarcinoma and with picoliter droplet digital PCR.
Results: A total of 135 patients with resectable (n = 31; 23%), locally advanced (n = 36; 27%), or metastatic (n = 68; 50%) pancreatic adenocarcinoma were included. In patients with advanced pancreatic adenocarcinoma (n = 104), 48% (n = 50) had ctDNA detectable with a median mutation allelic frequency (MAF) of 6.1%. The presence of ctDNA was strongly correlated with poor overall survival (OS; 6.5 vs. 19.0 months; P &lt; 0.001) in univariate and multivariate analyses (HR = 1.96; P = 0.007). To evaluate the impact of ctDNA level, patients were grouped according to MAF tertiles: OS were 18.9, 7.8, and 4.9 months (P &lt; 0.001). Among patients who had curative intent resection (n = 31), 6 had ctDNA detectable after surgery, with an MAF of 4.4%. The presence of ctDNA was associated with a shorter disease-free survival (4.6 vs.17.6 months; P = 0.03) and shorter OS (19.3 vs. 32.2 months; P = 0.027).
Conclusions: ctDNA is an independent prognostic marker in advanced pancreatic adenocarcinoma. Furthermore, it arises as an indicator of shorter disease-free survival in resected patients when detected after surgery. Clin Cancer Res; 23(1); 116–23. ©2016 AACR.
Characterization of an Abiraterone Ultraresponsive Phenotype in Castration-Resistant Prostate Cancer Patient-Derived Xenografts
Authors: Lam Hung-Ming , McMullin Ryan , Nguyen Holly M. , Coleman Ilsa , Gormley Michael , Gulati Roman , Brown Lisha G. , Holt Sarah K. , Li Weimin , Ricci Deborah S. , Verstraeten Karin , Thomas Shibu , Mostaghel Elahe A. , Nelson Peter S. , Vessella Robert L. , Corey Eva 
Published: December 2016

AbstractPurpose: To identify the molecular signature associated with abiraterone acetate (AA) response and mechanisms underlying AA resistance in castration-resistant prostate cancer patient-derived xenografts (PDXs).Experimental Design: SCID mice bearing LuCaP 136CR, 77CR, 96CR, and 35CR PDXs were treated with AA. Tumor volume and prostate-specific antigen were monitored, and tumors were harvested 7 days after treatment or at end of study for gene expression and immunohistochemical studies.Results: Three phenotypic groups were observed based on AA response. An ultraresponsive phenotype was identified in LuCaP 136CR with significant inhibition of tumor progression and increased survival, intermediate responders LuCaP 77CR and LuCaP 96CR with a modest tumor inhibition and survival benefit, and LuCaP 35CR with minimal tumor inhibition and no survival benefit upon AA treatment. We identified a molecular signature of secreted proteins associated with the AA ultraresponsive phenotype. Upon resistance, AA ultraresponder LuCaP 136CR displayed reduced androgen receptor (AR) signaling and sustainably low nuclear glucocorticoid receptor (nGR) localization, accompanied by steroid metabolism alteration and epithelial–mesenchymal transition phenotype enrichment with increased expression of NF-κB–regulated genes; intermediate and minimal responders maintained sustained AR signaling and increased tumoral nGR localization.Conclusions: We identified a molecular signature of secreted proteins associated with AA ultraresponsiveness and sustained AR/GR signaling upon AA resistance in intermediate or minimal responders. These data will inform development of noninvasive biomarkers predicting AA response and suggest that further inhibition along the AR/GR signaling axis may be effective only in AA-resistant patients who are intermediate or minimal responders. These findings require verification in prospective clinical trials. Clin Cancer Res; 23(9); 2301–12. ©2016 AACR.
A sociedade de rostos. Mulheres sem rosto como indício de novo humanismo nas redes sociais
Authors: Anchieta Isabelle 
Published: December 2016

Neste artigo busco entender de que forma a crescente importância da imagem humana _gradativamente individualizada_ instaura e testemunha novas formas de organização e integração social no sec. XXI. Apresento como asimagens nas redes sociais podem agenciar mudanças na relação de poder entre os indivíduos, os Estados Nação, a cultura local e as desigualdades estereotípicas (étnicas, raciais e sexuais) em defesa de algo que os transcende e os liga. Momento em que o rosto emerge como imagem da humanidade. Parto para esta reflexão de seu avesso: a ausência de uma face. O drama de mulheres paquistanesas que tiveram seus rostos desfigurados por ácido por seus companheiros _ uma prática cultural que se agrava desde o ano de 1999. Irei problematizar a circulação, o debate e a solidariedade que essa incomoda imagem despertou nas redes sociais brasileiras. Pretendo entender de que forma a violência contra a expressão mais visível da identidade social promove uma comoção para além das fronteiras nacionais e simbólicas, instaurando a ideia de humanidade.
A Negra de... e Moolaadè. Que África e teorias as lentes de Ousmane Sembène nos revelam?
Authors: Magno Maria Ignes Carlos , Torres Celia Cristina 
Published: December 2016

A sugestão dos filmes A Negra de... e Moolaadè do cineasta senegalês Osmane Sembène foi pensada no sentido de propor o conhecimento do cinema africano. A intenção aqui é aprender a olhar a África e suas histórias sob a lente de um diretor africano e as teorias que subjazem no interior das narrativas fílmicas.
Nkx2‐5 Is Expressed in Atherosclerotic Plaques and Attenuates Development of Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Du Meng , Wang Xiaojing , Tan Xin , Li Xiangrao , Huang Dandan , Huang Kun , Yang Liu , Zhang Fengxiao , Wang Yan , Huang Dan , Huang Kai 
Published: December 2016

Background

NK
2 homeobox 5 (Nkx2‐5) is a cardiac homeobox transcription factor that is expressed in a broad range of cardiac sublineages. Embryos lacking Nkx2‐5 are nonviable attributed to growth retardation and gross abnormalities of the heart. However, the role of Nkx2‐5 in atherosclerosis remains elusive. This study aims to elucidate the specific functions of Nkx2‐5 during atherogenesis and in established atherosclerotic plaques.

Methods and Results

Two types of atherosclerotic lesions were created in ApoE
−/−
mice through 2 different dietary manipulations. Mice fed a standard chow diet were sacrificed at 20 weeks old, a time point at which mice developed early‐stage atherosclerotic lesions. The other half of mice were fed a western diet from 6 to 22 weeks old and then sacrificed. These mice demonstrated advanced atherosclerosis. No Nkx2‐5 was detected in normal arteries; however, it was abundantly present in the intima of atherosclerotic lesions and localized in macrophages and smooth muscle cells. Adenovirus gene transfer of Nkx2‐5 markedly ameliorated and stabilized the atherosclerotic plaques, and knockdown of Nkx2‐5 significantly exacerbated the disease. Molecular studies indicated that expression of specific members of matrix metalloproteinases and tissue inhibitor of metalloproteinases, which play a crucial role in the progression of atherosclerosis, were directly regulated by Nkx2‐5. Furthermore, we demonstrated that the compromised endothelial function, which was considered as a hallmark of early atherosclerosis, could be improved by Nkx2‐5 gene transfer.

Conclusions
Nkx2‐5 exerts antiatherogenic effects, which may partly be attributed to regulation on matrix metalloproteinases and tissue inhibitor of metalloproteinases, thus stabilizing atherosclerotic plaque; besides, it improves endothelial function by inhibiting leukocyte adhesion to the endothelium.
北京話清入字歸調的內部演化視角
Authors: Wang Hongzhi 
Published: December 2016

This paper analyzes the re-classification of the Ru tone with voiceless initials in Beijing dialect from the perspective of internal development. The main factors that cause the Ru tone to change into four different unchecked tones are the laryngealization feature accompanying the loss of stop endings and the rotary change of high and low in the unchecked tones.
本文從內部音變的角度重新闡釋北京話清入歸派現象，認為清入字韻尾消失後對音節發聲形成的緊喉音色，以及北京話聲調調值的高低環流變化是造成清入字派入四聲的原因。(This article is in Chinese.)
再論 “陰出陽收” —— 從語言接觸的角度看
Authors: Shi Menghui 
Published: December 2016

This paper provides an explanation for yinchuyangshou 陰出陽收 in Duquxuzhi 度曲須知 written by Shen Chongsui 沈寵綏 in the Ming Dynasty. Based on the reconstruction, we propose that yinchuyangshou is designed to help speakers of the Wu dialects to learn the sound feature [voiceless fricative] in Mandarin. This explanation not only reflects the contact between Mandarin and Wu dialects, but is also in keeping with the acoustic analysis of xia 匣 initial in the modern Suzhou dialect.
本文主要認為沈寵綏《度曲須知》中所謂“陰出陽收”之概念，是要求吳人在唱曲時，注意某些字需要向當時已經發生濁音清化、並有“平送仄不送”的北方官話學習[清擦音]的特徵，這是“陰出”；而“陽收”則是指保持吳語本有陽平聲調的發音特性。“陰出陽收”和吳語的“清音濁流”關係不大。文章從沈氏論著的內部證據出發，按照其標注體系的一致性，結合現代語音學的分類，歸納出630個例字在北方話中都含有[清擦音]的統一聲學特徵。又從今蘇州方言的角度出發，通過歷時比較，證明了這種觀點。最後分析了蘇州方言匣母字的歷時變化，認為“陰出陽收”與今蘇州部分匣母 [hɦ] 的讀音有關，是一種人為的語言接觸，明朝中葉蘇州方言的匣母字應該就是吳語的原生一分類型 [ɦ]。(This article is in Chinese.)
西夏韻書分轉所反映的複聲母與韻母系統
Authors: Zhengzhang Shangfang 
Published: December 2016

The reconstruction of Tangut pronunciation has been advanced by several scholars. Gong Hwang-cherng’s reconstruction is even more outstanding. His remarkable insight is that the third and the fourth class (děng) belonging to different rhymes have the same reconstruction. However, his Tangut reconstruction, with few consonant clusters, resembles Loloish rather than Qiangic. The present study puts forward that the Tangut rhyme dictionaries with 105 rhymes were made by simulating Chinese rhyme dictionaries. The six monophthongs “i, ɯ, u, e, a, o” and the two diphthongs “eu, ou” form eight broad rhyme groups (shè). The first class has no (or -0) medial; the second class the -r medial; the third and the fourth classes the -j medial. A class is divided into four turns (zhuǎn): the first turn (R1-60) has the zero, nasal or w- pre-initial; the second turn (R61-75) has the l-, s- or x- pre-initial; the third turn (R76-98) has the r- pre-initial (similar to M. V. Sofronov’s proposal); the fourth turn (R99-105) is for further supplements. The author reconstructs phonetic values for the rhymes of each turn. Hereby, the system of the consonant clusters in Tangut can be regularly reconstructed according to the phonological records in the rhyme dictionaries. This solution is further supported by observations on some languages related to Qiangic. When we compare several cognates and morphological changes in the Horpa language, we can see some items similar to the present reconstruction.
西夏文擬音經海內外諸家研究已經取得很大成就，龔煌城先生的系統更為出色，三四等不同韻而擬音相同尤為高見。惜複輔音擬得太少，以致面貌不像羌語支語言而像彝語。本文提出西夏韻書分105韻乃依傍漢語等韻，本六元音i、ɯ、u、e、a、o加eu、ou合為八攝，依聲母墊尾性質分一等 -∅、二等 -r、三四等 -j，各攝元音重複迴環再分為四轉。分轉所據不是韻母元音本身區別，乃兼顧前接聲母的冠音區別：1轉（R1-60）為∅- 冠、鼻冠、w- 冠，2轉（R61-75）為l-、s-、x- 冠，3轉（R76-98）為r- 冠（蘇敏也曾提r-），4轉（R99-105擴至七韻）補遺特讀。並為每轉各韻具體擬音。據此西夏語複輔音系統可按韻書音韻地位有規律恢復。此乃觀察羌語支近緣語言所得結果，試比較西夏近緣的道孚等語言同源詞與語法變化，可看到與以上擬音相近似的變化。(This article is in Chinese.)
Trends in CMIP5 Rainfall Patterns over Southwestern Australia
Authors: Raut Bhupendra A. , Reeder Michael J. , Jakob Christian 
Published: December 2016

Abstract
Previous work has shown that the sharp fall in winter rainfall over coastal southwestern Australia in the 1970s was mainly due to a fall in the frequency of fronts; the gradual reduction in rainfall since the late 1990s was due to a reduction in the number of light-rain days; and the increased inland summer rainfall in the 1970s was due to an increased number of easterly troughs. The current paper extends this earlier work by identifying the rainfall patterns in the region in 14 CMIP5 models for the period 1980–2005 and by calculating how these patterns are projected to change in the twenty-first century. The patterns are identified using k-means clustering of the rainfall, which are validated against observed rainfall clusters. Although the agreement between the models and the observation is generally good, the models underestimate the frequency of raining fronts. In both representative concentration pathway 4.5 and 8.5 (RCP4.5 and RCP8.5) scenarios the number of dry days increases significantly at the expense of light-rain days and frontal rainfall. However, these trends are twice as large in the RCP8.5 scenario as in the RCP4.5 scenario. The reduction in the rainfall from the historical period to the second half of the twenty-first century is produced mainly by a reduction in both the frequency and intensity of light rain and a reduction in the frequency of fronts in the westerlies.
Spatial Interpolation of Daily Precipitation in a High Mountainous Watershed Based on Gauge Observations and a Regional Climate Model Simulation
Authors: Wang Yuhan , Yang Hanbo , Yang Dawen , Qin Yue , Gao Bing , Cong Zhentao 
Published: December 2016

Abstract
Precipitation is a primary climate forcing factor in catchment hydrology, and its spatial distribution is essential for understanding the spatial variability of ecohydrological processes in a catchment. In mountainous areas, meteorological stations are generally too sparse to represent the spatial distribution of precipitation. This study develops a spatial interpolation method that combines meteorological observations and regional climate model (RCM) outputs. The method considers the precipitation–elevation relationship in the mountain region and the topographic effects, especially the mountain blocking effect. Furthermore, using this method, this study produced a 3-km-resolution precipitation dataset from 1960 to 2014 in the middle and upper reaches of the Heihe River basin located on the northern slope of the Qilian Mountains in the northeastern Tibetan Plateau. Cross validation based on the station observations showed that this method is reasonable. The rationality of the interpolated precipitation data was also evaluated by the catchment water balances using the observed river discharge and the actual evapotranspiration based on remote sensing. The interpolated precipitation data were compared with the China Gauge-Based Daily Precipitation Analysis product and the RCM output and was shown to be optimal. The results showed that the proposed method effectively used the information from the meteorological observations and the RCM simulations and provided the spatial distributions of daily precipitations with reasonable accuracy and high resolution, which is important for a distributed hydrological simulation at the catchment scale.
Regulation of ciliary retrograde protein trafficking by the Joubert syndrome proteins ARL13B and INPP5E
Authors: Nozaki Shohei , Katoh Yohei , Terada Masaya , Michisaka Saki , Funabashi Teruki , Takahashi Senye , Kontani Kenji , Nakayama Kazuhisa 
Published: December 2016

ABSTRACT
ARL13B (a small GTPase) and INPP5E (a phosphoinositide 5-phosphatase) are ciliary proteins encoded by causative genes of Joubert syndrome. We here showed, by taking advantage of a visible immunoprecipitation assay, that ARL13B interacts with the IFT46–IFT56 (IFT56 is also known as TTC26) dimer of the intraflagellar transport (IFT)-B complex, which mediates anterograde ciliary protein trafficking. However, the ciliary localization of ARL13B was found to be independent of its interaction with IFT-B, but dependent on the ciliary-targeting sequence RVEP in its C-terminal region. ARL13B-knockout cells had shorter cilia than control cells and exhibited aberrant localization of ciliary proteins, including INPP5E. In particular, in ARL13B-knockout cells, the IFT-A and IFT-B complexes accumulated at ciliary tips, and GPR161 (a negative regulator of Hedgehog signaling) could not exit cilia in response to stimulation with Smoothened agonist. This abnormal phenotype was rescued by the exogenous expression of wild-type ARL13B, as well as by its mutant defective in the interaction with IFT-B, but not by its mutants defective in INPP5E binding or in ciliary localization. Thus, ARL13B regulates IFT-A-mediated retrograde protein trafficking within cilia through its interaction with INPP5E.