bluuebunny/crossref_metadata_2025 huggingface dataset:
Instantaneous Amplitude‐Frequency Feature Extraction for Rotor Fault Based on BEMD and Hilbert Transform
Authors: Huang Chuanjin , Song Haijun , Lei Wenping , Niu Zhanya , Meng Yajun
Published: March 2019

The vibration signals propagating in different directions from rotating machines can contain a variety of characteristic information. A novel feature extraction method based on bivariate empirical mode decomposition (BEMD) for rotor is proposed to comprehensively extract the fault features. In this work, the number of signal projection directions is determined through simulation, and the energy end condition based on the energy threshold is increased using BEMD to enhance the decomposition quality. Mixed vibration signals are generated along two orthogonal directions. Then, the acquired vibration signal can be decomposed into several intrinsic mode functions (IMFs) at the rotational speed using the BEMD method. Furthermore, the instantaneous frequency and instantaneous amplitude of the real signals and the imaginary part of the IMF signals are obtained using the Hilbert transform. The fault features along two and three dimensions can be investigated, providing more comprehensive information to aid in the fault diagnosis of rotor. Experimental results on oil film oscillation, the oil whirl, the bistability of the rotor, and looseness and rotor rubbing composite fault indicate the effectiveness of the proposed method.
Insight into Neutrophil Extracellular Traps through Systematic Evaluation of Citrullination and Peptidylarginine Deiminases
Authors: Holmes Caitlyn L. , Shim Daeun , Kernien John , Johnson Chad J. , Nett Jeniel E. , Shelef Miriam A.
Published: March 2019

In rheumatoid arthritis, an autoimmune inflammatory arthritis, citrullinated proteins are targeted by autoantibodies and thus thought to drive disease. Neutrophil extracellular traps (NETs) are a source of citrullinated proteins and are increased in rheumatoid arthritis and therefore also implicated in disease pathogenesis. However, not all NETs are citrullinated. One theory aiming to clarify the intersection of citrullination, NETs, and rheumatoid arthritis suggests that specific stimuli induce different types of NETs defined by citrullination status. However, most studies do not evaluate uncitrullinated NETs, only citrullinated or total NETs. Further, the requirement for peptidylarginine deiminase (PAD) 2 and 4, two important citrullinating enzymes in neutrophils and rheumatoid arthritis, in the formation of different NETs has not been clearly defined. To determine if specific stimulants induce citrullinated or uncitrullinated NETs and if those structures require PAD2 or PAD4, human and murine neutrophils, including from PAD4-/- and PAD2-/- mice, were stimulated in vitro and NETs imaged and quantified. In humans, phorbol myristate acetate (PMA), ionomycin, monosodium urate (MSU), and Candida albicans induced NETs with MSU and C. albicans inducing primarily citrullinated, PMA primarily uncitrullinated, and ionomycin a mix of NETs. Only ionomycin and C. albicans were strong inducers of NETs in mice with ionomycin-induced NETs mostly citrullinated and C. albicans-induced NETs a mix of citrullinated and uncitrullinated. Interestingly, no stimulus induced exclusively citrullinated or uncitrullinated NETs. Further, PAD4 was required for citrullinated NETs only, whereas PAD2 was not required for either NET in mice. Therefore, specific stimuli induce varying proportions of both citrullinated and uncitrullinated NETs with different requirements for PAD4. These findings highlight the complexity of NET formation and the need to further define the mechanisms by which different NETs form and their implications for autoimmune disease.
Number of Spanning Trees in the Sequence of Some Graphs
Authors: Liu Jia-Bao , Daoud S. N.
Published: March 2019

In mathematics, one always tries to get new structures from given ones. This also applies to the realm of graphs, where one can generate many new graphs from a given set of graphs. In this work, using knowledge of difference equations, we drive the explicit formulas for the number of spanning trees in the sequence of some graphs generated by a triangle by electrically equivalent transformations and rules of weighted generating function. Finally, we compare the entropy of our graphs with other studied graphs with average degree being 4, 5, and 6.
EC‐Structure: Establishing Consumption Structure through Mining E‐Commerce Data to Discover Consumption Upgrade
Authors: Guo Lin , Zhang Dongliang
Published: March 2019

The traditional methods of analyzing consumption structure have many limitations, and data acquisition is difficult, so it is hard to scientifically verify the accuracy of algorithms. With the development of Internet economy, many scientific researchers focus on mining knowledge of consumer behavior using big data analysis technology. Because consumption decisions are influenced by not only personal characteristics but also social trends and environment, it is one‐sided to analyze the impact of one single factor on the phenomenon of consumption. The authors of this paper combine the consumption structure analysis method and data processing technology using data from an e‐commerce platform to extract the consumption structure of cities, compare the structural differences between different periods, and then discover consumption upgrading according to swarm intelligence. The experiments prove the efficacy of the algorithm proposed in this paper compared to other similar algorithms using several different datasets, which illustrates the algorithm’s efficacy and stable performance in consumption structure analysis.
A Case of Postpartum Anogenital Mammary-Like Gland Tumor with Focal Lactational Features: A Nomenclature Issue
Authors: Thiryayi Sakinah A. , Rouzbahman Marjan , Ghazarian Danny
Published: March 2019

Mammary-like glands (MLG) are considered to be a normal constituent of the anogenital region and can give rise to tumors with variable morphology that may be difficult to classify. We present a case of an anogenital mammary-like gland tumor in a breastfeeding woman showing morphological variation with lactational change, an unusual finding. We discuss the differing terminology used to report these tumors and the variation in assignment of their origin to MLG or ectopic breast tissue.
Passive Ultrasonic Irrigation Efficacy in the Vapor Lock Removal: Systematic Review and Meta-Analysis
Authors: Dioguardi Mario , Di Gioia Giovanni , Illuzzi Gaetano , Ciavarella Domenico , Laneve Enrica , Troiano Giuseppe , Lo Muzio Lorenzo
Published: March 2019

Passive Ultrasonic Irrigation (PUI) represents one of the most used systems to improve the endodontic irrigants activity. PUI acts increasing the reaction rate of NaOCl, with an increase of dentinal debris and smear layer removal. There is a stronger shear stress and a vapor lock reduction. Aim of this systematic review was to figure out the effects of the PUI on the vapor lock removal, during irrigation. Literature research has been carried out by two reviewers, consulting online databases such as PubMed, EBSCO, and Google Scholar, using keywords like Vapor Lock, Vapour Lock, and Vapor Lock Endodontic. The articles list has been screened based on titles and abstracts, applying eligibility and inclusion criteria. The three articles were eligible for quantitative and statistical analysis, by using RevManager Software Version 5.3. Results show statistical heterogeneity (P=0.08; I2index=61%) in the vapor lock elimination between the use of PUI and PPI, with an overall Odds Ratio=0.08, CI=95% [0.03;0.25]. PUI resulted to be a useful technique to improve NaOCl activity for vapor lock removal, despite PPI alone using a needle.
The Clinical and Vascular Characteristics of RNF213 c.14576G>A Variant-Related Intracranial Major Artery Disease in China
Authors: Cheng Weiyang , Xue Sufang , Wu Fang , Song Xiaowei , Huang Qiang , Song Haiqing , Wu Jian
Published: March 2019

Background and Purpose. Recently, several studies indicated the c.14576G>A variant on the ring finger protein 213 (RNF213), a founder variant of moyamoya diseases (MMD), was associated with non-MMD intracranial major artery stenosis/occlusion (non-MMD ICASO). We proposed that RNF213 variant-related ICASO including MMD might be a special entity with its own characteristics based on a genetic background. The aim of the study was to learn the clinical and vascular features of RNF213 variant-related ICASO. Moreover, we tried to explore the clinical significance of a testing variant in ICASO patients in China. Methods. Clinical material and routine image data were collected in 160 Chinese patients with ICASO, including 41 verified MMD and 119 non-MMD. DNA samples were extracted, and the c.14576G>A variant on RNF213 was genotyped. Then, the clinical and vascular features were compared between the patients with and without a relevant variant. Furthermore, the patients with RNF213 mutation were performed with high resolution magnetic resonance imaging (HR-MRI) examination to conclude features of the artery wall. Results. There were 16 (10%) patients (including 9 MMD and 7 non-MMD ICASO) presenting a heterozygous c.14576G>A variant while none of homozygote was found. Compared to the patients without the c.14576G>A variant, the variant group had more female, less symptomatic patients, and more possibility of having collateral vessels in vascular imaging. In the symptomatic subgroup, there is no significant difference in clinical presentation (p>0.05) between two groups. However, RNF213 variant-related ICASO had lower scores in NIHSS (1.0±3.0 vs. 3.9±5.0, p<0.05) but not in mRS. In the symptomatic subgroup, in addition, most of the HR-MRI images of variant ICASO (77.8%, 7 of 9) were characterized by a shrunken outer diameter, concentric thickening vessel wall, and collateral vessel structures on the stenotic portion, which was prone to be diagnosed as HR-MMD (a MMD diagnosis diagnosed by HR-MRI). The rest of the two variants showed a relatively eccentric luminal narrow, normal outer diameter without collateral vessel findings, identified as HR-ICAD (intracranial atherosclerotic disease diagnosed by HR-MRI). Conclusions. Our study demonstrated that the c.14576G>A variant on RNF213 may be a biomarker to good outcome of ICASO in Chinese. The variant-related ICASO was characterized by both features of MMD and ICAD diagnosed by HR-MRI.
Analysis of the Main Factors Influencing the Dominant Frequency of Blast Vibration
Authors: Liu Da , Lu Wenbo , Liu Yijia , Chen Ming , Yan Peng , Sun Pengchang
Published: March 2019

At present, the study on the dominant frequency of blasting vibration is still a worldwide problem. Compared with the mature research on the particle peak velocity of blasting vibration, the researches on the dominant frequency of blasting vibration are much less. In this paper, by analyzing the main influencing factors of the dominant frequency, an attenuation equation of the dominant frequency induced by blasting vibration has been proposed by dimensional analysis combined with the theory of radial spherical wave propagation. The proposed equation is applied to the fitting analysis on the dominant frequency measured in Zhoushan Green Petrochemical Base in China, which has obtained a favorable fitting correlation. Based on the fitting analysis, it has found that the correlation coefficient of radial vibration obtained by the proposed equation is higher than that of vertical vibration, which is resulted from the reason that the vibration in vertical is considered to be influenced most by the R‐wave on the ground and perceived to be quite different from the radial vibration affected by P‐wave. In generally, different components of blasting waves will affect the attenuation of dominant frequency.
Fast Determination of Auramine O in Food by Adsorptive Stripping Voltammetry
Authors: Nguyen Thi Kim Thuong , Bui Thi Thu , Pham Anh Tuan , Duong Van Thang , Le Thi Huong Giang
Published: March 2019

The electrochemical behaviour of auramine O on the hanging mercury drop electrode has been investigated by cyclic and square wave voltammetry method. Reduction peak of auramine O was irreversible and adsorptive on the hanging mercury drop electrode. The optimal conditions were chosen to be Briton–Robinson buffer pH 9.0, accumulation potential −0.5 V vs. Ag/AgCl/KCl, accumulation time 60 s, pulse amplitude 250 mV·s−1, and frequency 50 Hz. At the optimum experimental conditions, the peak of the target analyte was sharp and asymmetric. The linearity of the peak current depending on the concentration ranged from 4.0 × 10−8 to 6.4 × 10−7 mol L−1. The limit of detection and limit of quantitation were 2.46 × 10−8 mol L−1 and 8.21 × 10−8 mol L−1, respectively. The recovery and relative standard deviation were 94.9% and 2.0% (n = 5). The developed method was successfully applied to determine auramine O in chicken samples with an appropriate sample preparation.
Hybrid Degradation Equipment Remaining Useful Life Prediction Oriented Parallel Simulation considering Model Soft Switch
Authors: Ge Chenglong , Zhu Yuanchang , Di Yanqiang
Published: March 2019

Equipment parallel simulation is an emerging simulation technology in recent years, and equipment remaining useful life (RUL) prediction oriented parallel simulation is an important branch of parallel simulation. An important concept in equipment parallel simulation is the model evolution driven by real-time data, including model selection and model parameter evolution. The current research on equipment RUL prediction oriented parallel simulation mainly focuses on a single continuous degradation mode, such as linear degradation and nonlinear degradation. Under this degradation condition, the model parameter evolution methods in parallel simulation can effectively predict equipment RUL. However, in practice, most of the equipment degradation processes exhibit a mixture of continuous degradation and discrete shock. So this requires adaptive selection of simulation models based on real-time degradation data. In this paper, the hybrid degradation equipment RUL prediction oriented parallel simulation considering model soft switch is studied. Firstly, under the modeling framework of the state space model (SSM), two kinds of degradation simulation models are established using the Wiener process and Poisson effect. Driven by the real-time degradation data, the model probability is calculated by using the forward interactive multiple model filtering algorithm to realize the model soft switch and data assimilation. On the basis of model soft switch, the expectation maximization algorithm is utilized to achieve model parameter evolution. Through the iteration between model soft switch and model parameter evolution, the simulation fidelity can be effectively improved and the actual equipment degradation state is continuously approached. According to the full probability theorem and the concept of first hitting time, the simulated degradation state distribution is integrated into the inverse Gaussian distribution. Then the analytical expression of the RUL probability density function is obtained to achieve RUL real-time prediction. Finally, a case study was conducted by using a bearing degradation data. The results show that the parallel simulation can effectively model the hybrid degradation process of the bearing. Compared with the single-model method that only considers the model parameter evolution, the RUL obtained by the method proposed in this paper has higher prediction accuracy and smaller uncertainty.
Primary Tumor Site Affects Survival in Patients with Gastroenteropancreatic and Neuroendocrine Liver Metastases
Authors: Tierney John F. , Poirier Jennifer , Chivukula Sitaram , Pappas Sam G. , Hertl Martin , Schadde Erik , Keutgen Xavier
Published: March 2019

Background. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are commonly present with metastatic disease, and the liver is the most frequent metastatic site. Herein, we studied whether primary tumor site affects survival in patients with GEP-NETs and liver metastases (NELM). As a secondary endpoint, we studied whether extrahepatic disease and surgical resection impact survival in this patient population. Methods. Patients with NELM diagnosed from 2006 to 2014 were identified from the National Cancer Database. Kaplan-Meier curves and nested Cox proportional hazards were used to assess variables associated with survival. Results. 2947 patients with well- or moderately differentiated GEP-NETs and NELM met the inclusion criteria for this study. Patients with small bowel NETs survived the longest of all GEP-NETs with NELM (median not reached). Rectal and gastric NETs with NELM had the shortest survival (median 31 months). Patients with extrahepatic metastases who underwent any operation survived longer than those managed nonoperatively (median survival 38.7 months vs. 18.6 months, p=0.01). On multivariable analysis, operations on the primary tumor and distant metastatic site (HR 0.23-0.43 vs. no surgery), treatment at an academic/research hospital, Charlson comorbidity index of 0, no extrahepatic metastases, and younger age were associated with prolonged survival (p<0.01). Conclusions. Primary tumor site affects survival in patients with GEP-NETs and NELM. Surgical resection seems beneficial for all GEP-NETs with NELM, even in the presence of extrahepatic metastases.
HERC3-Mediated SMAD7 Ubiquitination Degradation Promotes Autophagy-Induced EMT and Chemoresistance in Glioblastoma
Authors: Li Hong , Li Junjie , Chen Lei , Qi Songtao , Yu Shishi , Weng Zhijian , Hu Ziyou , Zhou Qiang , Xin Zong , Shi Linyong , Ma Liyi , Huang Annie , Lu Yuntao
Published: March 2019

Purpose:

Glioblastoma, a common malignant intracranial tumor, has the most dismal prognosis. Autophagy was reported to act as a survival-promoting mechanism in gliomas by inducing epithelial-to-mesenchymal transition (EMT). Here, we determined the critical molecules involved in autophagy-induced EMT and elucidated the possible mechanism of chemoradiotherapy resistance and tumor recurrence.

Experimental Design:

We used isobaric tags for relative and absolute quantitation to identify the critical proteins and pathway mediating EMT via autophagy inducer treatment, and tested the expression of these proteins using tissue microarray of gliomas and clinical glioblastoma samples as well as tissues and cells separated from the core lesion and tumor-peripheral region. Analysis of the Cancer Genome Atlas database and 110 glioblastoma cases revealed the prognostic value of these molecules. The functional role of these critical molecules was further confirmed by in vitro experiments and intracranial xenograft in nude mice.

Results:

Autophagy inducers significantly upregulated the expression of HERC3, which promotes ubiquitination-mediated degradation of SMAD7 in an autolysosome-dependent manner. The corresponding increase in p-SMAD2/3 level and TGFβ pathway activation finally induced EMT in cell lines and primary glioblastoma cells. Moreover, HERC3 overexpression was observed in pseudo-palisade cells surrounding tumor necrosis and in tumor-adjacent tissue; high HERC3 and low SMAD7 levels predicted poor clinical outcome in glioblastoma; xenograft of nude mice and in vitro experiments confirmed these findings.

Conclusions:

Together, our findings reveal the indispensable role of HERC3 in regulating canonical SMAD2/3-dependent TGFβ pathway involvement in autophagy-induced EMT, providing insights toward a better understanding of the mechanism of resistance to temozolomide and peripheral recurrence of glioblastoma.
Mutant and Wild-Type Isocitrate Dehydrogenase 1 Share Enhancing Mechanisms Involving Distinct Tyrosine Kinase Cascades in Cancer
Authors: Chen Dong , Xia Siyuan , Wang Mei , Lin Ruiting , Li Yuancheng , Mao Hui , Aguiar Mike , Famulare Christopher A. , Shih Alan H. , Brennan Cameron W. , Gao Xue , Pan Yaozhu , Liu Shuangping , Fan Jun , Jin Lingtao , Song Lina , Zhou An , Mukherjee Joydeep , Pieper Russell O. , Mishra Ashutosh , Peng Junmin , Arellano Martha , Blum William G. , Lonial Sagar , Boggon Titus J. , Levine Ross L. , Chen Jing
Published: March 2019

Isocitrate dehydrogenase 1 (IDH1) is important for reductive carboxylation in cancer cells, and the IDH1 R132H mutation plays a pathogenic role in cancers including acute myeloid leukemia (AML). However, the regulatory mechanisms modulating mutant and/or wild-type (WT) IDH1 function remain unknown. Here, we show that two groups of tyrosine kinases (TK) enhance the activation of mutant and WT IDH1 through preferential Y42 or Y391 phosphorylation. Mechanistically, Y42 phosphorylation occurs in IDH1 monomers, which promotes dimer formation with enhanced substrate (isocitrate or α-ketoglutarate) binding, whereas Y42-phosphorylated dimers show attenuated disruption to monomers. Y391 phosphorylation occurs in both monomeric and dimeric IDH1, which enhances cofactor (NADP+ or NADPH) binding. Diverse oncogenic TKs phosphorylate IDH1 WT at Y42 and activate Src to phosphorylate IDH1 at Y391, which contributes to reductive carboxylation and tumor growth, whereas FLT3 or the FLT3-ITD mutation activates JAK2 to enhance mutant IDH1 activity through phosphorylation of Y391 and Y42, respectively, in AML cells.

Significance:

We demonstrated an intrinsic connection between oncogenic TKs and activation of WT and mutant IDH1, which involves distinct TK cascades in related cancers. In particular, these results provide an additional rationale supporting the combination of FLT3 and mutant IDH1 inhibitors as a promising clinical treatment of mutant IDH1-positive AML.

See related commentary by Horton and Huntly, p. 699.

This article is highlighted in the In This Issue feature, p. 681
Cytochrome bcc-aa3 Oxidase Supercomplexes in the Aerobic Respiratory Chain of Streptomyces coelicolor A3(2)
Authors: Falke Dörte , Fischer Marco , Biefel Bianca , Ihling Christian , Hammerschmidt Claudia , Reinefeld Kevin , Haase Alexander , Sinz Andrea , Sawers R. Gary
Published: March 2019

Streptomyces coelicolor A3(2), an obligately aerobic, oxidase-positive, and filamentous soil bacterium, lacks a soluble cytochrome c in its respiratory chain, having instead a membrane-associated diheme c-type cytochrome, QcrC. This necessitates complex formation to allow electron transfer between the cytochrome bcc and aa3 oxidase respiratory complexes. Combining genetic complementation studies with in-gel cytochrome oxidase activity staining, we demonstrate that the complete qcrCAB-ctaCDFE gene locus on the chromosome, encoding, respectively, the bcc and aa3 complexes, is required to manifest a cytochrome oxidase enzyme activity in both spores and mycelium of a qcr-cta deletion mutant. Blue-native-PAGE identified a cytochrome aa3 oxidase complex of approximately 270 kDa, which catalyzed oxygen-dependent diaminobenzidine oxidation without the requirement for exogenously supplied cytochrome c, indicating association with QcrC. Furthermore, higher molecular mass complexes were identified upon addition of soluble cytochrome c, suggesting the supercomplex is unstable and readily dissociates into subcomplexes lacking QcrC. Immunological and mass spectrometric analyses of active, high-molecular mass oxidase-containing complexes separated by clear-native PAGE identified key subunits of both the bcc complex and the aa3 oxidase, supporting supercomplex formation. Our data also indicate that the cytochrome b QcrB of the bcc complex is less abundant in spores compared with mycelium.
Novel Face-Name Paired Associate Learning and Famous Face Recognition in Mild Cognitive Impairment: A Neuropsychological and Brain Volumetric Study
Authors: Nanda Satyan , Mohanan Nandini , Kumari Sheela , Mathew Mridula , Ramachandran Sushama , Rajesh Pillai P.G. , Kesavadas Chandrasekharan , Sarma P. Sankara , Menon Ramshekhar N.
Published: March 2019

Purpose: To assess visual associative learning and famous face recognition ability among subjects with stable amnestic mild cognitive impairment (MCI) relative to early stage dementia due to Alzheimer’s disease (AD) and cognitively normal healthy controls (NC) and to correlate these differences with volumetric changes on MRI. Methods: A hospital-based cross-sectional observational study was conducted on 61 participants. The subjects underwent neuropsychological evaluation, including validated newly designed tests for novel face-name paired association learning recall and famous face recognition. MRI volumetry was done on a subset of patients to ascertain the topographical patterns of volume loss. Results: There were significant differences in performance on free recall for face-name paired associate learning in MCI (n = 22) compared to NC (n = 20) (p < 0.001) and MCI compared to AD (n = 19; p < 0.001). Significant differences were also noted in scores on the famous personalities test between MCI and NC (p = 0.007), and MCI and AD (p = 0.032). The free recall component of face-name pair associative learning significantly correlated with left cuneus (p = 0.005; r = 0.833) and right cuneus (p = 0.003; r = 0.861) volume in AD with no significant correlation among MCI and NC cohorts. Conclusions: Novel and semantically familiar face-name associative recalls are significantly impaired in MCI, and these potentially predate the MRI volumetric changes in MCI. Our findings expand the spectrum of recall deficits in MCI.
Alteração hidrotermal e fluidos mineralizantes no alvo Jerimum de Baixo, Campo Mineralizado do Cuiú-Cuiú, Província Aurífera do Tapajós: um estudo baseado em petrografia, inclusões fluidas e química mineral
Authors: Oliveira Helder Thadeu de , Borges Régis Munhoz Krás , Klein Evandro Luiz , Lamarão Claudio Nery , Marques Gisele Tavares , Lima Rafael Guimarães Correa
Published: March 2019

O alvo Jerimum de Baixo está localizado no Campo Mineralizado do Cuiú-Cuiú, região central da Província Aurífera do Tapajós, Cráton Amazônico. O alvo abrange rochas de composição monzogranítica portadoras de biotita rica em Fe, essencialmente isotrópicas e que foram de fraca a fortemente hidrotermalizadas. Cloritização, sericitização, sulfetação, silicificação e carbonatação são os tipos de alteração mais importantes. A clorita hidrotermal é do tipo chamosita e foi formada entre 261 e 315ºC. A mica branca apresenta composição fengítica. A mineralização é representada por vênulas de quartzo com baixo teor de sulfetos (pirita + pirrotita ± calcopirita ± galena ± esfalerita) em que o ouro ocorre livre e em zonas mais fragilizadas e alteradas, geralmente associado à pirrotita. O estudo petrográfico e microtermométrico de inclusões fluidas hospedadas em quartzo de vênulas definiu inclusões aquocarbônicas, carbônicas e aquosas. Os fluidos com CO2 representam o provável fluido mineralizador e foram gerados por processos de separação de fases entre 280 e 380ºC. Uma posterior infiltração e processos de mistura com fluidos meteóricos são indicados para os fluidos aquosos mais tardios. Separação de fases, modificações nas condições do pH e interação fluido/rocha foram os mecanismos importantes para a precipitação do Au, que se deu em nível rúptil-dúctil da crosta (entre 2 e 6 km). O conjunto de dados até aqui disponíveis indicam para o alvo Jerimum de Baixo uma filiação metalogenética similar a de depósitos auríferos relacionados à intrusão.
Uma historiografia sobre a "falta": a ditadura do general Alfredo Stroessner no Paraguai (1954-1989)
Authors: Silva Paulo Renato da
Published: March 2019

O objetivo deste artigo é analisar a historiografia sobre a ditadura do general Alfredo Stroessner (1954-1989) no Paraguai. Apesar das exceções e das mudanças em curso, consideramos que essa bibliografia especializada seja marcada pela perspectiva da “falta”, ou seja, os processos históricos paraguaios são analisados a partir daquilo que – supostamente – teria faltado ao país, desconsiderando suas particularidades, e alimenta as imagens do Paraguai como um país “isolado”, “atrasado” e “autoritário”.
Aprendendo a voar: James Aggrey e os anos de formação de Kwame Nkrumah
Authors: Paiva Felipe
Published: March 2019

A característica mais marcante do político e ideólogo ganês Kwame Nkrumah (1909-1972) é seu pan-africanismo radical. O significante África tinha para ele o sentido de nação a ser construída e reconquistada. Este ímpeto pan-africano foi fruto de um amadurecimento visível em sua trajetória. Nela, o educador ganês James Aggrey (1875-1927) desempenhou papel fundamental. Por meio de uma crítica da obra de Nkrumah e dos discursos e escritos de Aggrey abordamos neste artigo a relação intelectual entre ambos.
“Orientalismos” e Arquivos Esquecidos da Época Moderna
Authors: Gonçalves Margareth Almeida
Published: March 2019

Resenha do livro: XAVIER, Ângela Barreto & ŽUPANOV, Inês G. Catholic orientalism. Empire, Indian knowledge (16th-18th centuries). Nova Deli: Oxford University Press, 2015, 416 p.
First photographic evidence of polymorphic Asiatic Golden Cat Catopuma temminckii Vigors & Horsfield, 1827 (Mammalia: Carnivora: Felidae) in Buxa Tiger Reserve, West Bengal, India
Authors: Ghose Mayukh , Sharma Deepak , Murali Nandavaram Subbarao
Published: March 2019

During a camera trap survey in Buxa Tiger Reserve in West Bengal, India, individuals of Asiatic Golden Cat Catopuma temminckii were photographed between 13 and 26 February 2018.  The images provide the first photographic evidence of the species presence in this protected area.  Both golden and spotted individuals were recorded.
Small cat surveys: 10 years of data from Central Kalimantan, Indonesian Borneo
Authors: Jeffers Karen Anne , , Adul , Cheyne Susan Mary
Published: March 2019

We present an update on the photographic detections from camera traps and the activity patterns of Borneo’s four small cats, namely, Sunda Leopard Cat Prionailurus javanensis, Flat-headed Cat P. planiceps, Marbled Cat Pardofelis marmorata, and Bay Cat Catopuma badia, at two sites in Central Kalimantan, Indonesia.  Camera trap survey data of 10 years (2008–2018) from the first site in Sebangau provide details about the temporal partitioning of these small cats from each other but overlap with Sunda Clouded Leopard Neofelis diardi.  The activity of Flat-headed Cat was higher after midnight and that of Leopard Cat at night with no clear preference before or after midnight.  The Marbled Cat is predominantly diurnal, but the remaining three cats have flexible activity periods.  While limited data are available from Rungan, the second site, we confirmed the presence of all four small cat species found on Borneo, though we have insufficient data to comment on the Bay Cat.  The cat sightings, however, are intermittent and may reflect the unprotected status of this forest.  Leopard Cats appear relatively unaffected by habitat disturbance based on encounter rates on camera traps.  Conservationists, both NGOs and the government, must pay particular attention to specialists like Flat-headed Cats and Bay Cats when assessing habitat suitability for long-term cat conservation.
First photographic evidence of Fishing Cat Prionailurus viverrinus Bennett, 1833 and Clouded Leopard Neofelis nebulosa Griffith, 1821 (Carnivora: Felidae) in Parsa National Park, Nepal
Authors: Poudel Shashank , Lamichhane Babu Ram , Bhattarai Santosh , Adhikari Dipendra , Pokheral Chiranjibi Prasad , Bhatta Tek Raj , Giri Sailendra Raj , Lamichhane Saneer , Sadaula Amir , Gurung Ashish , Poudyal Laxman Prasad , Regmi Uba Raj , Subedi Naresh
Published: March 2019

Twelve cat species were recorded in Nepal including the largest, Tiger Panthera tigris, and the smallest, Rusty-spotted Cat Prionailurus rubiginosus.  There is more research on the Panthera species than on small wild cats; consequently, the conservation status, distribution, and ecology of small cat species are poorly known.  In this article, we report on the first photographic evidence of Clouded Leopard Neofelis nebulosa and Fishing Cat Prionailurus viverrinus in Parsa National Park in southern central Nepal during a camera trap survey targeted at the tiger between 2014 and 2016.  There were only single detections of each species; this does not give enough information to establish distribution or conservation status of either of the species in Parsa National Park.  Further targeted surveys are needed to establish the significance of this protected area for the conservation of these two species.
Abstract 014: Interferon-induced Transmembrane 3 (IFITM3) on Megakaryocytes and Platelets Regulates Fibrinogen Endocytosis and Thrombosis During Inflammation
Authors: Campbell Robert A , Manne Bhanu K , Saperstein Samantha , Page Lauren , Schwertz Hansjorg , Rowley Jesse W , Weyrich Andrew S , Rondina Matthew T
Published: March 2019

Introduction:
IFITM3, an interferon (IFN) responsive gene, restricts pathogen replication through vesicular trafficking mechanisms. IFITM3 in megakaryocytes (MKs) and platelets has not been examined. We hypothesized that in MKs and platelets, IFITM3 regulates the endocytosis of pro-coagulant proteins, aggregation, and thrombosis.

Methods:
the regulation of IFITM3 gene expression was determined in MKs and platelets under inflammatory stimuli. Fibrinogen (Fgn) endocytosis, a clathrin-mediated event requiring αIIbβ3, and transferrin endocytosis, a clathrin-mediated, αIIbβ3-independent event, were examined in stimulated MKs and platelets from wild type (WT) and Ifitm
-/-
mice (KO). Integrin αIIbβ3 activation, platelet aggregation, and thrombosis was determined in WT and Ifitm
-/-
mice upon IFNα-stimulation. Co-immunoprecipitation identified interaction partners for IFITM3. To establish human relevance, IFITM3 expression, Fgn content, and aggregation was measured in platelets from septic patients, where systemic IFNs are increased.

Results:
IFNs significantly induced IFITM3 expression in MKs and platelets (p<0.001). Upregulation of IFITM3 by IFNs increased Fgn and transferrin endocytosis in MKs (2-fold vs. NT, p<0.05). Co-IP demonstrated a specific IFITM3 interaction between clathrin and αIIb. Upon IFN stimulation, IFITM3, clathrin, and αIIb shifted into lipid rafts. Increased Fgn endocytosis by IFNs enhanced platelet aggregation and accelerated death (~2-fold increased) due to platelet-dependent thrombosis (p<0.05 for all comparisons). In KO mice, enhanced Fgn endocytosis, platelet aggregation, and thrombosis to IFNs was completely prevented, demonstrating the necessity of IFITMs for these functional responses. Platelets from septic patients mirrored findings in mice with a ~20-fold increase in IFITM3 protein expression, with shifts into lipid rafts, compared to healthy controls (p<0.0001). Increased platelet IFITM3 expression was associated with greater platelet Fgn content and significant increases in platelet aggregation (20% increase, p<0.05).

Conclusions:
Our data identify IFITM3 as a previously unknown regulator of MK and platelet endocytosis and thrombosis under inflammatory stimuli in humans and mice.
Abstract 037: Coagulation Factor XII Promotes Platelet Consumption in the Presence of Microbial Polyphosphate Under Shear Flow
Authors: Zilberman-Rudenko Jevgenia , Reitsma Stephanie E , Puy Cristina , Smith Stephanie A , Wiesenekker Chantal P , Tucker Erik I , Travers Richard J , Maas Coen , Urbanus Rolf T , Gailani David , Schmaier Alvin H , Lupu Florea , Morrissey James H , Gruber Andras , McCarty Owen J
Published: March 2019

Background:
Terminal complications of bacterial sepsis include development of disseminated intravascular consumptive coagulopathy. Bacterial constituents, including long-chain polyphosphates (polyP), have been shown to activate the contact pathway of coagulation in plasma. Recent work shows that activation of the contact pathway in flowing whole blood can promote thrombin generation and platelet activation and consumption distal to thrombus formation
ex vivo
and
in vivo
.

Aim:
Determine whether presence of long-chain polyP in the bloodstream promotes platelet activation and consumption in a coagulation factor (F)XII-dependent manner.

Methods/Results:
The addition of long-chain polyP to human whole blood promoted platelet P-selectin expression, microaggregate formation and platelet consumption in the bloodstream under shear in a FXII-dependent manner. Moreover, long-chain polyP accelerated thrombus formation on immobilized collagen surfaces under shear flow in a thrombin generation-dependent manner. Distal to the site of thrombus formation, platelet consumption was dramatically enhanced in the presence of long-chain polyP in the bloodstream. Inhibiting contact activation of coagulation using established and novel agents reduced fibrin formation on collagen as well as platelet consumption in the bloodstream distal to the site of thrombus formation.
In vivo
, FXII deficiency was protective against long-chain polyP occlusive lung thrombus formation in mice. Lastly, in a non-human primate model of sepsis, pretreatment of animals with an antibody blocking FXI activation by FXIIa (14E11) diminished LD
100
S. aureus
-induced platelet and fibrinogen consumption.

Conclusions:
This study demonstrates that bacterial-type long-chain polyP promotes FXII-mediated thrombin generation and platelet activation in the flowing blood and could contribute to sepsis-associated thrombotic processes, consumptive coagulopathy and thrombocytopenia.
Abstract 052: Clinical and Genetic Determinants of Varicose Veins: a Prospective, Community-Based Study of ~500,000 Individuals
Authors: Flores Alyssa M , Fukaya Eri , Lindholm Daniel , Gustafsson Stefan , Zanetti Daniela , Ingelsson Erik , Leeper Nicholas J
Published: March 2019

Background:
Varicose veins are a common problem with no approved medical therapies. While it is believed that varicose vein pathogenesis is multifactorial, there is a limited understanding of the genetic and environmental factors that contribute to their formation. Large-scale studies of risk factors for varicose veins may highlight important aspects of pathophysiology and identify groups at increased risk for disease.

Methods:
We applied machine learning to agnostically search for risk factors of varicose veins in 493,519 individuals in the UK Biobank. Predictors were further studied using univariable and multivariable Cox regression analysis. A genome-wide association study (GWAS) of varicose veins was also performed among 337,536 individuals (9,577 cases) of white British descent, followed by eQTL and pathway analyses. Because height emerged as a new candidate predictor, we used LD score regression to estimate the genetic correlation between height and varicose veins. Finally, we performed Mendelian randomization analyses to assess for a causal role for height in varicose vein disease.

Results:
Machine learning confirmed several known (age, gender, obesity, pregnancy, history of deep vein thrombosis) and identified several new risk factors for varicose vein disease. The most important novel predictors were leg bioimpedance (HR: 0.44, 95% CI: 0.39-0.50,
P
< 0.0001) and height (HR: 1.74; 95% CI: 1.51-2.01,
P
< 0.0001), which both remained independently associated with varicose veins after adjusting for traditional risk factors in Cox regression. A GWAS identified 30 new genome-wide significant loci, identifying pathways involved in vascular development and skeletal/limb biology. Mendelian randomization analysis provided evidence that increased height is causally related to varicose veins (IVW: beta = 0.266, P = 1.28 x 10
-16
).

Conclusions:
Using data from nearly half a million individuals, we identified novel clinical and genetic risk factors which provide pathophysiological insights and could help future improvements of treatment of varicose vein disease.
Abstract 054: Genetic Deficiency in Nox2-containing NADPH Oxidase Decreases Susceptibility to Venous Thrombosis in Mice
Authors: Sonkar Vijay K , Kumar Rahul , Gu Sean , Doddapattar Prakash , Lentz Steven R , Dayal Sanjana
Published: March 2019

Activated neutrophils release neutrophil extracellular traps (NETs) via a pathway dependent on reactive oxygen species (ROS). NETs are enriched in extracellular DNA and histones, and contribute to venous thrombosis. Nox2-containing NADPH oxidase is a major upstream mediator of ROS-dependent release of NETs. Neutrophils from mice deficient in Nox2 or patients with X-linked chronic granulomatous disease due to Nox2 deficiency do not produce NETs, suggesting a role for Nox2 in venous thrombosis. We hypothesized that mice genetically deficient in Nox2 are protected from venous thrombosis. We studied male and female mice deficient in Nox2 (Nox2-KO) and their wild type (WT) littermates at 10-14 weeks of age (n=7-13/group). Using electron spin resonance and H2C-DCFH-DA staining, we confirmed that neutrophils from Nox2-KO mice do not produce ROS at baseline or upon PMA-activation. Neutrophils from WT mice displayed a dose-dependent release of NETs upon PMA-stimulation (SYTOX green staining using fluorescence microscopy), whereas Nox2-KO mice did not produce NETs. We next examined susceptibility to venous thrombosis in a stasis model of inferior vena cava (IVC) ligation. After 48 hours of ligation, both male and female Nox2-KO mice developed significantly smaller thrombi compared with WT mice (P<0.05). Markers for NETs were measured in plasma (nucleosome levels using ELISA) and venous thrombi (staining for citrullinated histones, Cit-H3). Levels of nucleosomes in the mice that did not develop thrombi were similar to those in baseline samples collected before IVC ligation. All of the mice that developed thrombi had significant elevation of plasma nucleosome levels compared with mice that did not develop thrombi (P<0.05), but nucleosome levels did not differ between WT and Nox2-KO mice. Likewise, the heterogeneous pattern of NET formation within thrombi detected by Cit-H3 staining was similar in WT and Nox2-KO mice. These findings suggest that Nox2 is an important determinant of thrombus size during IVC ligation. Interestingly, our study also provides evidence for Nox2-independent pathways for NET release during venous thrombosis.
Abstract 056: Endothelial 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase, Isoform 3 (PFKFB3) Deficiency Inhibits Hypoxia-Induced Pulmonary Hypertension in Mice
Authors: Cao Yapeng , Yang Qiuhua , Wang Lina , Xu Jiean , Liu Zhiping , Xu Yiming , Wang Yong , Fulton David J , Weintraub Neal L , Wu Chaodong , Li Qinkai , Su Yunchao , Hong Mei , Huo Yuqing
Published: March 2019

Background:
Pulmonary artery hypertension (PAH) is a severe proliferative disease characterized by the remodeling of small pulmonary arteries leading to a progressive increase in pulmonary vascular resistance and ultimately to right ventricular failure and death. Many studies have indicated that endothelial dysfunction is a key element in the pathogenesis of this disease. In this study, we investigated whether endothelial glycolysis plays a critical role in the development of hypoxia-induced PAH by knocking down endothelial PFKFB3 (encoding 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform 3), a critical regulator of glycolysis.

Methods and Results:
Immunostaining results showed that pulmonary artery endothelial PFKFB3 was increased in the lung of PAH patients. Mice deficient in endothelial
Pfkfb3
showed decreased right ventricular systolic pressure, attenuated right ventricular hypertrophy and normal morphology of distal pulmonary arteries after four weeks of hypoxia compared with control mice. Furthermore, PFKFB3-deficient pulmonary arterial ECs secreted less growth factors, which ameliorated the proliferation of pulmonary artery smooth muscle cells. Additionally, the levels of endothelial derived inflammatory cytokines were also decreased. Besides, the inhibitory effect of endothelial
Pfkfb3
supression on PAH formation were demonstrated in Sugen 5416/hypoxia rat pulmonary hypertension model with 3PO, a specific PFKFB3 inhibitor. Mechanistically, genetic deletion of
PFKFB3
or 3PO treatment decreased the TNF-α induced NLRP3 inflammasome activation in pulmonary arterial ECs.

Conclusions:
Endothelial PFKFB3 inhibition is able to ameliorate the development of hypoxia-induced pulmonary hypertension.
Abstract 058: Efficacy and Mechanisms of Metformin Therapy in Established Experimental Abdominal Aortic Aneurysms
Authors: Xu Baohui , Li Gang , Shen Fanru , Weden Trevor , Cabot Anna , Deng Hongping , Chen Xiaofeng , Dalman Ronald L
Published: March 2019

Objective:
Diabetes reduces the risk for abdominal aortic aneurysm (AAA) disease. In prior work in rodent models, pre-treatment with metformin was protective against experimental AAA initiation and progression. This study examined the influence of metformin therapy on progression of existing experimental AAAs.

Methods:
AAAs were created in 10-12 week old male C57BL/6J mice via transient intra-aortic infusion of porcine pancreatic elastase (PPE). Mice were treated with metformin (250 mg/kg via oral gavage), metformin plus AMPK inhibitor Compound C (the later via 10 mg/kg intraperitoneal injection) or vehicle alone for 10 days starting on day 4 following AAA creation. Outcomes were assessed by serial transabdominal ultrasonographic assessment of aortic diameter during treatment, as well as histological examination at sacrifice.

Results:
The principal findings are summarized in the Figure. Vehicle-treated mice experienced progressive, time-dependent aortic enlargement from day 3 to 14 following PPE infusion. Metformin treatment substantially attenuated further enlargement of existing AAAs. Treatment with Compound C partially rescued the AAA phenotype in metformin-treated mice. Histologically, characteristic aneurysmal pathologic changes, including medial elastin degradation, smooth muscle cell (SMC) depletion, mural leukocyte accumulation and neoangiogenesis (assessed by CD31 staining), present in PPE-infused, vehicle-treated mice, were substantially attenuated with metformin treatment. Co-treatment with Compound C abrogated the effects of metformin on media elastin degradation, SMC depletion and mural macrophage infiltration, with less influence on mural angiogenesis.

Conclusion:
Metformin therapy suppresses further expansion of existing experimental AAAs. This effect is abrogated by co-treatment with Compound C. These findings further justify performance of a clinical trial of metformin for medical management of AAA disease.