bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive Intuitionistic Fuzzy Enhancement of Brain Tumor MR Images
Authors: Deng He , Deng Wankai , Sun Xianping , Ye Chaohui , Zhou Xin 
Published: October 2016

AbstractImage enhancement techniques are able to improve the contrast and visual quality of magnetic resonance (MR) images. However, conventional methods cannot make up some deficiencies encountered by respective brain tumor MR imaging modes. In this paper, we propose an adaptive intuitionistic fuzzy sets-based scheme, called as AIFE, which takes information provided from different MR acquisitions and tries to enhance the normal and abnormal structural regions of the brain while displaying the enhanced results as a single image. The AIFE scheme firstly separates an input image into several sub images, then divides each sub image into object and background areas. After that, different novel fuzzification, hyperbolization and defuzzification operations are implemented on each object/background area, and finally an enhanced result is achieved via nonlinear fusion operators. The fuzzy implementations can be processed in parallel. Real data experiments demonstrate that the AIFE scheme is not only effectively useful to have information from images acquired with different MR sequences fused in a single image, but also has better enhancement performance when compared to conventional baseline algorithms. This indicates that the proposed AIFE scheme has potential for improving the detection and diagnosis of brain tumors.
Infantile Hemangioma Originates From A Dysregulated But Not Fully Transformed Multipotent Stem Cell
Authors: Harbi Shaghayegh , Wang Rong , Gregory Michael , Hanson Nicole , Kobylarz Keith , Ryan Kamilah , Deng Yan , Lopez Peter , Chiriboga Luis , Mignatti Paolo 
Published: October 2016

AbstractInfantile hemangioma (IH) is the most common tumor of infancy. Its cellular origin and biological signals for uncontrolled growth are poorly understood, and specific pharmacological treatment is unavailable. To understand the process of hemangioma-genesis we characterized the progenitor hemangioma-derived stem cell (HemSC) and its lineage and non-lineage derivatives. For this purpose we performed a high-throughput (HT) phenotypic and gene expression analysis of HemSCs, and analyzed HemSC-derived tumorspheres. We found that IH is characterized by high expression of genes involved in vasculogenesis, angiogenesis, tumorigenesis and associated signaling pathways. These results show that IH derives from a dysregulated stem cell that remains in an immature, arrested stage of development. The potential biomarkers we identified can afford the development of diagnostic tools and precision-medicine therapies to “rewire” or redirect cellular transitions at an early stage, such as signaling pathways or immune response modifiers.
Synchronizing stochastic circadian oscillators in single cells of Neurospora crassa
Authors: Deng Zhaojie , Arsenault Sam , Caranica Cristian , Griffith James , Zhu Taotao , Al-Omari Ahmad , Schüttler Heinz-Bernd , Arnold Jonathan , Mao Leidong 
Published: October 2016

AbstractThe synchronization of stochastic coupled oscillators is a central problem in physics and an emerging problem in biology, particularly in the context of circadian rhythms. Most measurements on the biological clock are made at the macroscopic level of millions of cells. Here measurements are made on the oscillators in single cells of the model fungal system, Neurospora crassa, with droplet microfluidics and the use of a fluorescent recorder hooked up to a promoter on a clock controlled gene-2 (ccg-2). The oscillators of individual cells are stochastic with a period near 21 hours (h), and using a stochastic clock network ensemble fitted by Markov Chain Monte Carlo implemented on general-purpose graphical processing units (or GPGPUs) we estimated that >94% of the variation in ccg-2 expression was stochastic (as opposed to experimental error). To overcome this stochasticity at the macroscopic level, cells must synchronize their oscillators. Using a classic measure of similarity in cell trajectories within droplets, the intraclass correlation (ICC), the synchronization surface ICC is measured on >25,000 cells as a function of the number of neighboring cells within a droplet and of time. The synchronization surface provides evidence that cells communicate, and synchronization varies with genotype.
The robustness of ecosystems to the species loss of community
Authors: Cai Qing , Liu Jiming 
Published: October 2016

AbstractTo study the robustness of ecosystems is crucial to promote the sustainable development of human society. This paper aims to analyze the robustness of ecosystems from an interesting viewpoint of the species loss of community. Unlike the existing definitions, we first introduce the notion of a community as a population of species belonging to the same trophic level. We then put forward a novel multiobjective optimization model which can be utilized to discover community structures from arbitrary unipartite networks. Because an ecosystem is commonly represented as a multipartite network, we further introduce a mechanism of competition among species whereby a multipartite network is transformed into a unipartite signed network without loss of species interaction information. Finally, we examine three strategies to test the robustness of an ecosystem. Our experiments indicate that ecosystems are robust to random species loss of community but fragile to target ones. We also investigate the relationships between the robustness of an ecosystem and that of its community composed network both to species loss. Our experiments indicate that the robustness analysis of a large-scale ecosystem to species loss may be akin to that of its community composed network which is usually small in size.
The conformational dynamics of H2-H3n and S2-H6 in gating ligand entry into the buried binding cavity of vitamin D receptor
Authors: Tee Wei-Ven , Ripen Adiratna Mat , Mohamad Saharuddin Bin 
Published: October 2016

AbstractCrystal structures of holo vitamin D receptor (VDR) revealed a canonical conformation in which the ligand is entrapped in a hydrophobic cavity buried in the ligand-binding domain (LBD). The mousetrap model postulates that helix 12 is positioned away from the domain to expose the interior cavity. However, the extended form of helix 12 is likely due to artifacts during crystallization. In this study, we set out to investigate conformational dynamics of apo VDR using molecular dynamics simulation on microsecond timescale. Here we show the neighboring backbones of helix 2-helix 3n and beta strand 2-helix 6 of LBD, instead of the helix 12, undergo large-scale motion, possibly gating the entrance of ligand to the ligand binding domain. Docking analysis to the simulated open structure of VDR with the estimated free energy of −37.0 kJ/mol, would emphasise the role of H2-H3n and S2-H6 in facilitating the entrance of calcitriol to the LBD of VDR.
Goblet Cell Hyperplasia Requires High Bicarbonate Transport To Support Mucin Release
Authors: Gorrieri Giulia , Scudieri Paolo , Caci Emanuela , Schiavon Marco , Tomati Valeria , Sirci Francesco , Napolitano Francesco , Carrella Diego , Gianotti Ambra , Musante Ilaria , Favia Maria , Casavola Valeria , Guerra Lorenzo , Rea Federico , Ravazzolo Roberto , Di Bernardo Diego , Galietta Luis J. V. 
Published: October 2016

AbstractGoblet cell hyperplasia, a feature of asthma and other respiratory diseases, is driven by the Th-2 cytokines IL-4 and IL-13. In human bronchial epithelial cells, we find that IL-4 induces the expression of many genes coding for ion channels and transporters, including TMEM16A, SLC26A4, SLC12A2, and ATP12A. At the functional level, we find that IL-4 enhances calcium- and cAMP-activated chloride/bicarbonate secretion, resulting in high bicarbonate concentration and alkaline pH in the fluid covering the apical surface of epithelia. Importantly, mucin release, elicited by purinergic stimulation, requires the presence of bicarbonate in the basolateral solution and is defective in cells derived from cystic fibrosis patients. In conclusion, our results suggest that Th-2 cytokines induce a profound change in expression and function in multiple ion channels and transporters that results in enhanced bicarbonate transport ability. This change is required as an important mechanism to favor release and clearance of mucus.
Antioxidant and Antitumor Activity of a Bioactive Polyphenolic Fraction Isolated from the Brewing Process
Authors: Tatullo Marco , Simone Grazia Maria , Tarullo Franco , Irlandese Gianfranco , Vito Danila De , Marrelli Massimo , Santacroce Luigi , Cocco Tiziana , Ballini Andrea , Scacco Salvatore 
Published: October 2016

AbstractThere is increasing interest in identifying natural bioactive compounds that can improve mitochondrial functionality and regulate apoptosis. The brewery industry generates wastewater that could yield a natural extract containing bioactive phenolic compounds. Polyphenols act as antioxidants and have been documented to protect the human body from degenerative diseases such as cardiovascular diseases or cancer. The main aims of our research were to determine the phenolic profile of a crude extract obtained (at pilot scale) from a brewery waste stream and to evaluate the biochemical activity of this extract on the mitochondrial function of a cancer cell line (SH-SY5Y). This work is a basic translational pilot study. The total phenolic content was determined by the Folin–Ciocalteu assay, which revealed that 2.30% of the extract consisted of phenolic compounds. The polyphenols, identified and quantified by reverse-phase-high-performance liquid chromatography and mass spectrometry (RP-HPLC/MS), were mainly flavonoids. After cell culture, the tumoral cells treated with the polyphenolic extract showed enhanced mitochondrial oxidative function, which is likely related to a decrease in oxidative stress and an increase in mitochondrial biogenesis. This type of brewery waste stream, properly treated, may be a promising source of natural antioxidants to replace the synthetic antioxidants currently used in the food industry.
Prevalence of hemorrhagic fever with renal syndrome in Qingdao City, China, 2010–2014
Authors: Jiang Fachun , Zhang Zhentang , Dong Liyan , Hao Bi , Xue Zaifeng , Ma Dongqiang , Su Hang , Wen Hong-ling , Yu Hao , Yu Xue-jie 
Published: October 2016

AbstractHemorrhagic fever with renal syndrome (HFRS) was considered to be transmitted by Apodemus agrarius and Rattus norvegicus, the principal animal hosts of Hantaan virus and Seoul virus, respectively. The aim of this study is to determine the correlation of HFRS incidence with capture rate and hantavirus infection rate of rodent species in Qingdao City, China. We collected HFRS patients’ information and captured field and residential rodents in Qingdao City, China from 2010 to 2014. The correlations of HFRS incidence to rodent capture rate and hantavirus infection rate of rodents were analyzed statistically. The main findings of this study are that the high HFRS incidence (19.3/100,000) is correlated to the capture rate of field Mus musculus (p = 0.011, r = 0.037); but surprisingly it did not correlated to the capture rate of the principal rodent hosts Apodemus agrarius and Rattus norvegicus and the hantavirus infection rate of these rodent species in the field or residential area. These novel findings suggest that Mus musculus, a nontraditional animal host of hantavirus may play an important role in hantavirus transmission in Qingdao City.
Non-toxigenic environmental Vibrio cholerae O1 strain from Haiti provides evidence of pre-pandemic cholera in Hispaniola
Authors: Azarian Taj , Ali Afsar , Johnson Judith A. , Jubair Mohammad , Cella Eleonora , Ciccozzi Massimo , Nolan David J. , Farmerie William , Rashid Mohammad H. , Sinha-Ray Shrestha , Alam Meer T. , Morris J. Glenn , Salemi Marco 
Published: October 2016

AbstractVibrio cholerae is ubiquitous in aquatic environments, with environmental toxigenic V. cholerae O1 strains serving as a source for recurrent cholera epidemics and pandemic disease. However, a number of questions remain about long-term survival and evolution of V. cholerae strains within these aquatic environmental reservoirs. Through monitoring of the Haitian aquatic environment following the 2010 cholera epidemic, we isolated two novel non-toxigenic (ctxA/B-negative) Vibrio cholerae O1. These two isolates underwent whole-genome sequencing and were investigated through comparative genomics and Bayesian coalescent analysis. These isolates cluster in the evolutionary tree with strains responsible for clinical cholera, possessing genomic components of 6th and 7th pandemic lineages, and diverge from “modern” cholera strains around 1548 C.E. [95% HPD: 1532–1555]. Vibrio Pathogenicity Island (VPI)-1 was present; however, SXT/R391-family ICE and VPI-2 were absent. Rugose phenotype conversion and vibriophage resistance evidenced adaption for persistence in aquatic environments. The identification of V. cholerae O1 strains in the Haitian environment, which predate the first reported cholera pandemic in 1817, broadens our understanding of the history of pandemics. It also raises the possibility that these and similar environmental strains could acquire virulence genes from the 2010 Haitian epidemic clone, including the cholera toxin producing CTXϕ.
RSK1 protects P-glycoprotein/ABCB1 against ubiquitin–proteasomal degradation by downregulating the ubiquitin-conjugating enzyme E2 R1
Authors: Katayama Kazuhiro , Fujiwara Chiaki , Noguchi Kohji , Sugimoto Yoshikazu 
Published: October 2016

AbstractP-glycoprotein (P-gp) is a critical determinant of multidrug resistance in cancer. We previously reported that MAPK inhibition downregulates P-gp expression and that P-gp undergoes ubiquitin–proteasomal degradation regulated by UBE2R1 and SCFFbx15. Here, we investigated the crosstalk between MAPK inhibition and the ubiquitin–proteasomal degradation of P-gp. Proteasome inhibitors or knockdown of FBXO15 and/or UBE2R1 cancelled MEK inhibitor-induced P-gp downregulation. RSK1 phosphorylated Thr162 on UBE2R1 but did not phosphorylate FBXO15. MEK and RSK inhibitors increased UBE2R1-WT but not UBE2R1-T162D and -T162A expression. UBE2R1-T162D showed higher self-ubiquitination and destabilisation than UBE2R1-WT and -T162A. Unlike UBE2R1-WT and -T162A, UBE2R1-T162D did not induce P-gp ubiquitination. UBE2R1-WT or -T162A downregulated P-gp expression and upregulated rhodamine 123 level and sensitivity to vincristine and doxorubicin. However, UBE2R1-T162D did not confer any change in P-gp expression, rhodamine 123 accumulation and sensitivity to the drugs. These results suggest that RSK1 protects P-gp against ubiquitination by reducing UBE2R1 stability.
Fully automated grey and white matter spinal cord segmentation
Authors: Prados Ferran , Cardoso M. Jorge , Yiannakas Marios C. , Hoy Luke R. , Tebaldi Elisa , Kearney Hugh , Liechti Martina D. , Miller David H. , Ciccarelli Olga , Wheeler-Kingshott Claudia A. M. Gandini , Ourselin Sebastien 
Published: October 2016

AbstractAxonal loss in the spinal cord is one of the main contributing factors to irreversible clinical disability in multiple sclerosis (MS). In vivo axonal loss can be assessed indirectly by estimating a reduction in the cervical cross-sectional area (CSA) of the spinal cord over time, which is indicative of spinal cord atrophy, and such a measure may be obtained by means of image segmentation using magnetic resonance imaging (MRI). In this work, we propose a new fully automated spinal cord segmentation technique that incorporates two different multi-atlas segmentation propagation and fusion techniques: The Optimized PatchMatch Label fusion (OPAL) algorithm for localising and approximately segmenting the spinal cord, and the Similarity and Truth Estimation for Propagated Segmentations (STEPS) algorithm for segmenting white and grey matter simultaneously. In a retrospective analysis of MRI data, the proposed method facilitated CSA measurements with accuracy equivalent to the inter-rater variability, with a Dice score (DSC) of 0.967 at C2/C3 level. The segmentation performance for grey matter at C2/C3 level was close to inter-rater variability, reaching an accuracy (DSC) of 0.826 for healthy subjects and 0.835 people with clinically isolated syndrome MS.
Global mapping of antibody recognition of the hepatitis C virus E2 glycoprotein: Implications for vaccine design
Authors: Pierce Brian G. , Keck Zhen-Yong , Lau Patrick , Fauvelle Catherine , Gowthaman Ragul , Baumert Thomas F. , Fuerst Thomas R. , Mariuzza Roy A. , Foung Steven K. H. 
Published: October 2016

Significance
Hepatitis C virus is a major public health concern, infecting approximately 3% of the world’s population, with no vaccine currently available. To enable rational vaccine design for this highly diverse and dynamic virus, we performed alanine scanning of nearly all positions of the E2 envelope protein, which is the primary target of the antibody response, using a panel of 16 human monoclonal antibodies that target a broad range of epitopes. This approach provided an unprecedented global view of the determinants of E2 stability, residue connectivity, and neutralizing antibody recognition. These insights and mapping data provide a framework to engineer E2 to modulate antibody recognition and optimize its capacity to induce broadly neutralizing antibodies in the context of a vaccine.
Liberal Pluralism
Authors: Mookherjee Monica 
Published: October 2016

Recalling J. S. Mill’s consciousness of the different goals of human life, the modern debate about pluralism has gathered momentum in liberal philosophy largely as a consequence of the intellectual historian and political theorist Isaiah Berlin. In his seminal essay, “Two Concepts of Liberty,” Berlin prompted thought about the potential overlap between the plurality of human values and the liberal tradition. In the years following, a vigorous debate with numerous strands has arisen around a synthesis of these concepts, in the form of the theory of “liberal pluralism.” A key area of controversy is whether the acceptance of pluralism supports a “perfectionist” theory of the state; or whether, by contrast, it generates a neutral liberalism that abstains from difficult questions about the highest good. A related question is whether the concepts of liberal pluralism fit together at all. Some of Berlin’s interpreters such as John Gray suggest that value pluralism does not privilege liberalism, and that the relationship between these ideas is historically contingent. Liberal pluralists such as George Crowder disagree. From their perspective, liberals defend first-order political values such as fairness or personal autonomy, to protect the various conceptions of the good life citizens personally endorse. Moreover, the most recent decades have seen a burgeoning examination by analytical political theorists of the implications of liberal pluralism for state neutrality and the protection of minority cultural or religious rights. While the equally vast literature on toleration, political liberalism, and the politics of recognition is not considered in depth in this article, unless it explicitly invokes the theory of liberal pluralism, key works that apply liberal pluralism to minority cultural, religious, and ethnic identities are represented in the later sections. Therefore, this article overall reflects different dimensions of debate on a complex and much debated contemporary theory. Following the overview of Foundational Works, and background readings on the relationship between liberalism and the politics of difference and identity, the next substantive section covers critical studies of Berlin’s liberal pluralism. This is then followed by a section addressing the conceptual relationship between value pluralism and liberalism generally, before moving on to consider more specific works addressing the relation between liberal pluralism and the concept of neutrality. The final sections consider critical literature applying liberal pluralism to conditions of ethnic, subnational, cultural, and religious diversity. This is crucial, because the defense of liberal pluralist theories is clearly designed to be applied to such real-world situations of diversity.
Multidrug Resistant Pseudomonas aeruginosa Causing Prosthetic Valve Endocarditis: A Genetic-Based Chronicle of Evolving Antibiotic Resistance
Authors: Domitrovic T. Nicholas , Hujer Andrea M. , Perez Federico , Marshall Steven H. , Hujer Kristine M. , Woc-Colburn Laila E. , Parta Mark , Bonomo Robert A. 
Published: October 2016

Abstract
Background.  Successful treatment of infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa is thwarted by the emergence of antibiotic resistance and biofilm formation on prosthetic devices. Our aims were to decipher the molecular basis of resistance in a unique case of prosthetic valve endocarditis (PVE) caused by MDR P. aeruginosa.
Methods.  Five sequential MDR P. aeruginosa blood isolates collected during a 7-month period were recovered from a patient suffering from PVE previously exposed to β-lactam antibiotics. Minimum inhibitory concentrations (MICs) of several classes of antibiotics were used to indicate clinical resistance characteristics; relatedness of the isolates was determined using multilocus sequence typing and repetitive sequence-based polymerase chain reaction. Amplification and sequencing of regulatory and resistance genes was performed.
Results.  All isolates belonged to ST 298, possessed blaPDC-16, and were resistant to fluoroquinolones and carbapenems. In the course of therapy, we observed a &gt;2-fold increase in cephalosporin resistance (4 µg/mL to &gt;16 µg/mL). Sequencing of the AmpC regulator, ampR, revealed a D135N point mutation in cephalosporin-resistant isolates. Common carbapenemase genes were not identified. All isolates demonstrated a premature stop codon at amino acid 79 of the outer membrane protein OprD and mutations in the quinolone resistance-determining regions of gyrA and parC. Point mutations in nalC, an efflux pump regulator, were also observed.
Conclusions.  In this analysis, we chart the molecular evolution of β-lactam resistance in a case of PVE. We show that mutations in regulatory genes controlling efflux and cephalosporinase production contributed to the MDR phenotype.
Analysis of the Survival of Arterialized Venous Toenail Flap with Reference to Changes in Blood Circulation during the Postoperative Period in 2 Patients
Authors: Ishii Naohiro , Shimizu Yusuke , Aoki Marie , Suzuki Ayaka , Kishi Kazuo 
Published: October 2016

Summary:
Various techniques for nail reconstruction have been reported until now; however, a simple one providing good esthetic results was difficult to find. Arterialized venous toenail flap is a free flap that includes the nail bed and matrix with a pedicle formed solely by the subcutaneous vein of the toe. The use of this flap is minimally invasive and easy, and the flap has a high survival rate. The mechanism of graft survival remains unknown given the nonphysiologic circulation. To the best of our knowledge, no studies have explained this mechanism with reference to detailed postoperative course. We herein present 2 cases of nail reconstruction performed using arterialized venous toenail flap. We analyzed the postoperative course in detail, which enabled us to postulate on the mechanism of graft survival.
Platelet-derived Factor Concentrates with Hyaluronic Acid Scaffolds for Treatment of Deep Burn Wounds
Authors: Mashiko Takanobu , Minabe Toshiharu , Yamakawa Tomomi , Araki Jun , Sano Hitomi , Yoshimura Kotaro 
Published: October 2016

Summary:
A deep burn wound is a critical condition that generally necessitates vascularized tissue coverage. We performed the injection of platelet-derived factor concentrates combined with non–cross-linked hyaluronic acid scaffolds for 2 patients with critical burn wounds with bone and tendon exposure and achieved successful healing. Hyaluronic acid was considered to have served as a controlled-release carrier of platelet-derived factors, being clinically effective for the treatment of deep burn wounds.