bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oligocene slow and Miocene–Quaternary rapid deformation and uplift of the Yumu Shan and North Qilian Shan: evidence from high-resolution magnetostratigraphy and tectonosedimentology
Authors: Fang Xiaomin , Liu Dongliang , Song Chunhui , Dai Shuang , Meng Qingquan 
Published: November 2012

Abstract
Most existing tectonic models suggest Pliocene–Quaternary deformation and uplift of the NE Tibetan Plateau in response to the collision of India with Asia. Within the NE Tibetan Plateau, growth of the terranes was suggested to progress northeastward with the Yumu Shan (mountain) at the northeasternmost corner of the Qilian Shan (mountains) being uplifted only since about 1 Ma ago. Here we present a detailed palaeomagnetic dating and tectonosedimentological measurement of Cenozoic sediments in the eastern Jiuquan Basin related to the deformation and uplift of the North Qilian Shan and Yumu Shan. The results show that the eastern Jiuquan Basin is a Cenozoic foreland basin and received sediments at about 27.8 Ma at the latest. Eight subsequent tectonic events at about 27.8, 24.6, 13.7–13, 9.8–9.6, 5.1–3.6, 2.8–2.6, 0.8 and 0.1 Ma demonstrate the development of the foreland basin in response to Oligocene–Quaternary uplift of the North Qilian Shan and subsequent propagation of thrust–fold system owing to collision of India with Asia. The Yumu Shan is the late phase of deformation front in the thrust–fold system and commenced rapid uplift at about 9.8–9.6 Ma at the latest. A rigid block-floating model is proposed to interpret the mechanism of this deformation and uplift history.
Targeted Delivery of Paclitaxel to EphA2-Expressing Cancer Cells
Authors: Wang Si , Noberini Roberta , Stebbins John L. , Das Swadesh , Zhang Ziming , Wu Bainan , Mitra Sayantan , Billet Sandrine , Fernandez Ana , Bhowmick Neil A. , Kitada Shinichi , Pasquale Elena B. , Fisher Paul B. , Pellecchia Maurizio 
Published: November 2012

AbstractPurpose: YSA is an EphA2-targeting peptide that effectively delivers anticancer agents to prostate cancer tumors. Here, we report on how we increased the drug-like properties of this delivery system.Experimental Design: By introducing non-natural amino acids, we have designed two new EphA2 targeting peptides: YNH, where norleucine and homoserine replace the two methionine residues of YSA, and dYNH, where a D-tyrosine replaces the L-tyrosine at the first position of the YNH peptide. We describe the details of the synthesis of YNH and dYNH paclitaxel conjugates (YNH-PTX and dYNH-PTX) and their characterization in cells and in vivo.Results: dYNH-PTX showed improved stability in mouse serum and significantly reduced tumor size in a prostate cancer xenograft model and also reduced tumor vasculature in a syngeneic orthotopic allograft mouse model of renal cancer compared with vehicle or paclitaxel treatments.Conclusion: This study reveals that targeting EphA2 with dYNH drug conjugates could represent an effective way to deliver anticancer agents to a variety of tumor types. Clin Cancer Res; 19(1); 128–37. ©2012 AACR.
Cancer-Specific Requirement for BUB1B/BUBR1 in Human Brain Tumor Isolates and Genetically Transformed Cells
Authors: Ding Yu , Hubert Christopher G. , Herman Jacob , Corrin Philip , Toledo Chad M. , Skutt-Kakaria Kyobi , Vazquez Julio , Basom Ryan , Zhang Bin , Risler Jennifer K. , Pollard Steven M. , Nam Do-Hyun , Delrow Jeffery J. , Zhu Jun , Lee Jeongwu , DeLuca Jennifer , Olson James M. , Paddison Patrick J. 
Published: November 2012

Abstract
To identify new candidate therapeutic targets for glioblastoma multiforme, we combined functional genetics and glioblastoma network modeling to identify kinases required for the growth of patient-derived brain tumor–initiating cells (BTIC) but that are dispensable to proliferating human neural stem cells (NSC). This approach yielded BUB1B/BUBR1, a critical mitotic spindle checkpoint player, as the top-scoring glioblastoma lethal kinase. Knockdown of BUB1B inhibited expansion of BTIC isolates, both in vitro and in vivo, without affecting proliferation of NSCs or astrocytes. Mechanistic studies revealed that BUB1B's GLE2p-binding sequence (GLEBS) domain activity is required to suppress lethal kinetochore–microtubule (KT–MT) attachment defects in glioblastoma isolates and genetically transformed cells with altered sister KT dynamics, which likely favor KT–MT instability. These results indicate that glioblastoma tumors have an added requirement for BUB1B to suppress lethal consequences of altered KT function and further suggest that sister KT measurements may predict cancer-specific sensitivity to BUB1B inhibition and perhaps other mitotic targets that affect KT–MT stability.
Significance: Currently, no effective therapies are available for glioblastoma, the most frequent and aggressive brain tumor. Our results suggest that targeting the GLEBS domain activity of BUB1B may provide a therapeutic window for glioblastoma, as the GLEBS domain is nonessential in untransformed cells. Moreover, the results further suggest that sister KT distances at metaphase may predict sensitivity to anticancer therapeutics targeting KT function. Cancer Discov; 3(2); 198–211. ©2012 AACR.
See related commentary by Venere et al., p. 141
This article is highlighted in the In This Issue feature, p. 125
Association Between 2 Angiographic Subtypes of Renal Artery Fibromuscular Dysplasia and Clinical Characteristics
Authors: Savard Sébastien , Steichen Olivier , Azarine Arshid , Azizi Michel , Jeunemaitre Xavier , Plouin Pierre-François 
Published: November 2012

Background—
Initially based on histology, the diagnosis of renal artery fibromuscular dysplasia (FMD) is now based mostly on angiographic appearance because arterial tissue samples are rarely available. This retrospective cross-sectional study aimed to assess the clinical relevance of a binary angiographic classification of FMD lesions (unifocal or multifocal) based on computed tomographic or magnetic resonance angiography.

Methods and Results—
Adult patients diagnosed with FMD in a single tertiary care center for hypertension management were identified by screening of electronic files. FMD lesions were reviewed and classified according to computed tomography or magnetic resonance angiography as multifocal if there were at least 2 stenoses in the same arterial segment; otherwise, they were classified as unifocal. Of 337 patients with established renal artery FMD, 276 (82%) were classified as multifocal. Patients with unifocal and multifocal lesions differed significantly in median age at diagnosis of FMD (30 and 49 years) and hypertension (26 and 40 years), sex distribution (female:male ratio, 2:1 and 5:1), initial blood pressure (157/97 and 146/88 mm Hg), current smoking (50% and 26%), prevalence of unilateral renal artery lesions (79% and 38%), presence of kidney asymmetry (33% and 10%), renal revascularization procedures (90% and 35%), and hypertension cure rates in patients who underwent revascularization (54% and 26%).

Conclusions—
A binary angiographic classification into unifocal or multifocal renal artery FMD is straightforward and discriminates 2 groups of patients with different clinical phenotypes.
Cytochrome P450 Subfamily 2J Polypeptide 2 Expression and Circulating Epoxyeicosatrienoic Metabolites in Preeclampsia
Authors: Herse Florian , LaMarca Babbette , Hubel Carl A. , Kaartokallio Tea , Lokki A. Inkeri , Ekholm Eeva , Laivuori Hannele , Gauster Martin , Huppertz Berthold , Sugulle Meryam , Ryan Michael J. , Novotny Sarah , Brewer Justin , Park Joon-Keun , Kacik Michael , Hoyer Joachim , Verlohren Stefan , Wallukat Gerd , Rothe Michael , Luft Friedrich C. , Muller Dominik N. , Schunck Wolf-Hagen , Staff Anne C. , Dechend Ralf 
Published: November 2012

Background—
Preeclampsia is a multisystem disorder of pregnancy, originating in the placenta. Cytochrome P450 (CYP)-dependent eicosanoids regulate vascular function, inflammation, and angiogenesis, which are mechanistically important in preeclampsia.

Methods and Results—
We performed microarray screening of placenta and decidua (maternal placenta) from 25 preeclamptic women and 23 control subjects. The CYP subfamily 2J polypeptide 2 (CYP2J2) was upregulated in preeclamptic placenta and decidua. Reverse-transcription polymerase chain reaction confirmed the upregulation, and immunohistochemistry localized CYP2J2 in trophoblastic villi and deciduas at 12 weeks and term. The CYP2J2 metabolites, 5,6-epoxyeicosatrienoic acid (EET), 14,15-EET, and the corresponding dihydroxyeicosatrienoic acids, were elevated in preeclamptic women compared with controls in the latter two thirds of pregnancy and after delivery. Stimulating a trophoblast-derived cell line with the preeclampsia-associated cytokine tumor necrosis factor-α enhanced CYP2J2 gene and protein expression. In 2 independent rat models of preeclampsia, reduced uterine-perfusion rat and the transgenic angiotensin II rat, we observed elevated EET, dihydroxyeicosatrienoic acid, and preeclamptic features that were ameliorated by the CYP epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MsPPOH). Uterine arterial rings of these rats also dilated in response to MsPPOH. Furthermore, 5,6-EET could be metabolized to a thromboxane analog. In a bioassay, 5,6-EET increased the beating rate of neonatal cardiomyocytes. Blocking thromboxane synthesis reversed that finding and also normalized large-conductance calcium-activated potassium channel activity.

Conclusions—
Our data implicate CYP2J2 in the pathogenesis of preeclampsia and as a potential candidate for the disturbed uteroplacental remodeling, leading to hypertension and endothelial dysfunction.
Relational Features in Fine-Grained Opinion Analysis
Authors: Johansson Richard , Moschitti Alessandro 
Published: November 2012

Fine-grained opinion analysis methods often make use of linguistic features but typically do not take the interaction between opinions into account. This article describes a set of experiments that demonstrate that relational features, mainly derived from dependency-syntactic and semantic role structures, can significantly improve the performance of automatic systems for a number of fine-grained opinion analysis tasks: marking up opinion expressions, finding opinion holders, and determining the polarities of opinion expressions. These features make it possible to model the way opinions expressed in natural-language discourse interact in a sentence over arbitrary distances. The use of relations requires us to consider multiple opinions simultaneously, which makes the search for the optimal analysis intractable. However, a reranker can be used as a sufficiently accurate and efficient approximation. A number of feature sets and machine learning approaches for the rerankers are evaluated. For the task of opinion expression extraction, the best model shows a 10-point absolute improvement in soft recall on the MPQA corpus over a conventional sequence labeler based on local contextual features, while precision decreases only slightly. Significant improvements are also seen for the extended tasks where holders and polarities are considered: 10 and 7 points in recall, respectively. In addition, the systems outperform previously published results for unlabeled (6 F-measure points) and polarity-labeled (10–15 points) opinion expression extraction. Finally, as an extrinsic evaluation, the extracted MPQA-style opinion expressions are used in practical opinion mining tasks. In all scenarios considered, the machine learning features derived from the opinion expressions lead to statistically significant improvements.
An Assessment of Six Dissimilarity Metrics for Climate Analogs
Authors: Grenier Patrick , Parent Annie-Claude , Huard David , Anctil François , Chaumont Diane 
Published: November 2012

AbstractSpatial analog techniques consist in identifying locations whose historical climate is similar to the anticipated future climate at a reference location. In the process of identifying analogs, one key step is the quantification of the dissimilarity between two climates separated in time and space, which involves the choice of a metric. In this study, six a priori suitable metrics are described (the standardized Euclidean distance, the Kolmogorov–Smirnov statistic, the nearest-neighbor distance, the Zech–Aslan energy statistic, the Friedman–Rafsky runs statistic, and the Kullback–Leibler divergence) and criteria are proposed and investigated in an attempt to identify the best metric for selecting spatial analogs. The case study involves the use of numerical simulations performed with the Canadian Regional Climate Model (CRCM, version 4.2.3), from which three annual indicators (total precipitation, heating degree-days, and cooling degree-days) are calculated over 30-yr periods (1971–2000 and 2041–70). It is found that the six metrics identify comparable analog regions at a relatively large scale but that best analogs may differ substantially. For best analogs, it is shown that the uncertainty stemming from the metric choice does not generally exceed that stemming from the simulation or model choice. On the basis of the set of criteria considered in this study, the Zech–Aslan energy statistic stands out as the most recommended metric for analog studies, whereas the Friedman–Rafsky runs statistic is the least recommended.
West African Monsoon Intraseasonal Variability: A Precipitable Water Perspective
Authors: Poan D. Emmanuel , Roehrig Romain , Couvreux Fleur , Lafore Jean-Philippe 
Published: November 2012

Abstract
West African monsoon intraseasonal variability has important implications for food security and drought early warnings. In the present study, intraseasonal variability over the Sahel is assessed from the perspective of precipitable water, as provided by model reanalyses and GPS measurements. In the eastern Sahel, precipitable water variability is dominated by time scales longer than 10 days, whereas synoptic scales dominate in the western Sahel, especially because of African easterly waves (AEWs).
The present work then focuses on the moisture footprint of AEWs along the northern side of the African easterly jet, as detected and analyzed directly from the main synoptic disturbances associated with precipitable water. Composite wet and dry precipitable water anomalies within AEWs propagate westward with a 5–6-day period. Their robustness, consistency, and spatial footprint, as well as their significant modulation of the convective activity, imply potential skill for short- to medium-range forecasts of wet and dry events over the Sahel. A composite moisture budget points out the key processes involved in the evolution of moisture anomalies. Advection processes are shown to be dominant during their life cycle. A linear adiabatic analysis of the propagation and growth of AEW precipitable water anomalies captures the main observed properties well, even though a key role of diabatic processes such as rain evaporation is needed to fully understand the life cycle of such precipitable water anomalies, especially their growth over the continent.
Cetuximab infusion reactions: French pharmacovigilance database analysis
Authors: Grandvuillemin Aurélie , Disson-Dautriche Anne , Miremont-Salamé Ghada , Fourrier-Reglat Annie , Sgro Catherine ,   The Réseau des Centres Régionaux de Pharmacovigilance Français
Published: November 2012

Objectives: To compare characteristics of patients exhibiting cetuximab infusion reactions or another adverse drug reaction related to cetuximab and to identify factors associated with the severity of cetuximab infusion reactions. Methods: All cases of adverse drug reaction reported with cetuximab from 1985 to 2010 were extracted from the French Pharmacovigilance database. The severity of infusion reactions was assessed according to the NCI-CTCAE criteria (v4.0). Multiple logistic regression analysis was performed to identify factors associated with the severity of infusion reactions. Results: Among the 602 adverse drug reaction reported with cetuximab during the study period, 374 infusion reactions were identified. Indication is more likely to be head and neck than colorectal cancer among patients experiencing an infusion reaction ( p < 0.001). Among the seven deaths related to an infusion reaction, five patients were treated for head and neck cancer. Infusion reactions were more likely to be severe when they occurred during the first administration (OR = 7.40 95% CI [2.21–24.71]), adjusted for age, sex, region of France, quarter of the year, indication, year of occurrence, and premedication. Conclusion: Our study found that reports of infusion reactions more often concerned patients treated for head and neck cancer, that in these patients the adverse drug reaction was more often fatal and severe infusion reactions were more likely during the first administration. In daily practice, the close monitoring of patients during the first infusion, especially patients with head and neck cancer, is recommended. Considering the possible immunoglobulin E–mediated mechanism, reliable tests for their detection need to be readily available.
The M235T polymorphism in the angiotensinogen gene and heart failure: a meta-analysis
Authors: Chen Song , Zhang Lan , Wang Hong-Wei , Wang Xiao-Yun , Li Xue-Qi , Zhang Li-Li 
Published: November 2012

Background: The aim of the present study was to assess the association between M235T polymorphism and heart failure using a meta-analysis. Methods: A literature search of Google Scholar, PubMed, the Cochrane Library and the China National Knowledge Infrastructure database (January 1990–April 2012) was performed for relevant studies. Statistical analyses were carried out using the Stata 12.0 to combine all the relevant studies. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated in a fixed-effects model and a random-effects model when appropriate. The pooled ORs were performed under the allelic contrast (T vs M), the dominant (TT + MT vs. MM) and the recessive models (TT vs MT + MM). Begg’s test was used to measure publication bias. Results: A total of six case-control studies including 842 patients and 1054 controls were enrolled in this meta-analysis. Overall, there was a significant association between angiotensinogen (AGT) gene M235T polymorphism and risk of heart failure in the subgroup analysis under the allelic contrast (T vs M: OR = 1.48, 95% CI: 1.04–2.11) and the dominant model (TT+MT vs MM: OR=1.67, 95% CI: 1.13–2.46) in the Caucasian population. Conclusions: The current meta-analysis suggests that M235T polymorphism might be associated with increased risk of heart failure in Caucasians.
Esophageal dilation with integrated balloon imaging: initial evaluation in a porcine model
Authors: O’Dea John , Siersema Peter D. 
Published: November 2012

Background: When treating achalasia, balloon dilation is often combined with fluoroscopy to allow the lower esophageal sphincter to be visualized as it is being dilated. We sought to evaluate a new balloon dilation technology, EsoFLIP, which allows the shape of the balloon to be visualized in a nonradiographic manner by using impedance planimetry electrodes located within the dilation balloon. Methods: Two pigs weighing 35 kg were used. The EsoFLIP balloon dilator was introduced under endoscopic visualization. Successive injections of 50, 60, 70 and 85 mL into the dilation balloon permitted dilations at increasing diameters to be achieved. Following each dilation fluid was withdrawn to leave 30 mL in the balloon and an EsoFLIP image was captured to track progressive dilation of the gastroesophageal junction (GEJ). Results: The EsoFLIP catheter was safely deployed in the two pigs and no complications were noted. For pig 1, during dilation, the measured balloon diameter at the waist was 24.1, 28.9, 29.2 and 30.0 mm for balloon dilation volumes of 50, 60, 70 and 85 mL respectively. For pig 2 the corresponding diameter at the waist was 22.8, 27.1, 28.5 and 29.4 mm. The GEJ diameter increased from 12.5 and 12.4 mm to 17.4 and 17.5mm for pigs 1 and 2 respectively. Distensibility of the GEJ in pig 1 increased from 2.3 mm2/mmHg before to 4.4 mm2/mmHg after dilation and in pig 2 from 4.4 to 9.6 mm2/mmHg. The GEJ substantively achieved its final diameter after the dilation using just 50 mL in the balloon. Conclusions: We demonstrated technical feasibility and safety of the EsoFLIP dilator in a porcine model. Further studies in humans with achalasia remain to be conducted, which, besides demonstrating technical feasibility, should also evaluate the use of distensibility measurements taken during dilation to predict outcomes.
JAK2V617F activates Lu/BCAM-mediated red cell adhesion in polycythemia vera through an EpoR-independent Rap1/Akt pathway
Authors: De Grandis Maria , Cambot Marie , Wautier Marie-Paule , Cassinat Bruno , Chomienne Christine , Colin Yves , Wautier Jean-Luc , Le Van Kim Caroline , El Nemer Wassim 
Published: November 2012

Abstract
Polycythemia vera (PV) is characterized by an increased RBC mass, spontaneous erythroid colony formation, and the JAK2V617F mutation. PV is associated with a high risk of mesenteric and cerebral thrombosis. PV RBC adhesion to endothelial laminin is increased and mediated by phosphorylated erythroid Lu/BCAM. In the present work, we investigated the mechanism responsible for Lu/BCAM phosphorylation in the presence of JAK2V617F using HEL and BaF3 cell lines as well as RBCs from patients with PV. High levels of Rap1-GTP were found in HEL and BaF3 cells expressing JAK2V617F compared with BaF3 cells with wild-type JAK2. This finding was associated with increased Akt activity, Lu/BCAM phosphorylation, and cell adhesion to laminin that were inhibited by the dominant-negative Rap1S17N or by the specific Rap1 inhibitor GGTI-298. Surprisingly, knocking-down EpoR in HEL cells did not alter Akt activity or cell adhesion to laminin. Our findings reveal a novel EpoR-independent Rap1/Akt signaling pathway that is activated by JAK2V617F in circulating PV RBCs and responsible for Lu/BCAM activation. This new characteristic of JAK2V617F could play a critical role in initiating abnormal interactions among circulating and endothelial cells in patients with PV.
Differential interactions of virulent and non-virulent H. parasuis strains with naïve or swine influenza virus pre-infected dendritic cells
Authors: Mussá Tufária , Rodríguez-Cariño Carolina , Sánchez-Chardi Alejandro , Baratelli Massimiliano , Costa-Hurtado Mar , Fraile Lorenzo , Domínguez Javier , Aragon Virginia , Montoya María 
Published: November 2012

Abstract
Pigs possess a microbiota in the upper respiratory tract that includes Haemophilus parasuis. Pigs are also considered the reservoir of influenza viruses and infection with this virus commonly results in increased impact of bacterial infections, including those by H. parasuis. However, the mechanisms involved in host innate responses towards H. parasuis and their implications in a co-infection with influenza virus are unknown. Therefore, the ability of a non-virulent H. parasuis serovar 3 (SW114) and a virulent serovar 5 (Nagasaki) strains to interact with porcine bone marrow dendritic cells (poBMDC) and their modulation in a co-infection with swine influenza virus (SwIV) H3N2 was examined. At 1 hour post infection (hpi), SW114 interaction with poBMDC was higher than that of Nagasaki, while at 8 hpi both strains showed similar levels of interaction. The co-infection with H3N2 SwIV and either SW114 or Nagasaki induced higher levels of IL-1β, TNF-α, IL-6, IL-12 and IL-10 compared to mock or H3N2 SwIV infection alone. Moreover, IL-12 and IFN-α secretion differentially increased in cells co-infected with H3N2 SwIV and Nagasaki. These results pave the way for understanding the differences in the interaction of non-virulent and virulent strains of H. parasuis with the swine immune system and their modulation in a viral co-infection.