bluuebunny/crossref_metadata_2025_split huggingface dataset:
YAP Subcellular Localization and Hippo Pathway Transcriptome Analysis in Pediatric Hepatocellular Carcinoma
Authors: LaQuaglia Michael J. , Grijalva James L. , Mueller Kaly A. , Perez-Atayde Antonio R. , Kim Heung Bae , Sadri-Vakili Ghazaleh , Vakili Khashayar 
Published: September 2016

AbstractPediatric hepatocellular carcinoma (HCC) is a rare tumor which is associated with an extremely high mortality rate due to lack of effective chemotherapy. Recently, the Hippo pathway and its transcriptional co-activator Yes-associated protein (YAP) have been shown to play a role in hepatocyte proliferation and development of HCC in animal models. Therefore, we sought to examine the activity of YAP and the expression of Hippo pathway components in tumor and non-neoplastic liver tissue from 7 pediatric patients with moderately differentiated HCC. None of the patients had underlying cirrhosis or viral hepatitis, which is commonly seen in adults with HCC. This highlights a major difference in the pathogenesis of HCC between children and adults. We found a statistically significant increase in YAP nuclear localization in 100% of tumors. YAP target gene (CCNE1, CTGF, Cyr61) mRNA expression was also increased in the tumors that had the most significant increase in YAP nuclear localization. Based on Ki67 co-localization studies YAP nuclear localization was not simply a marker of proliferation. Our results demonstrate a clear increase in YAP activity in moderately differentiated pediatric HCC, providing evidence that it may play an important role in tumor survival and propagation.
Magnetic resonance imaging reveals functional anatomy and biomechanics of a living dragon tree
Authors: Hesse Linnea , Masselter Tom , Leupold Jochen , Spengler Nils , Speck Thomas , Korvink Jan Gerrit 
Published: September 2016

AbstractMagnetic resonance imaging (MRI) was used to gain in vivo insight into load-induced displacements of inner plant tissues making a non-invasive and non-destructive stress and strain analysis possible. The central aim of this study was the identification of a possible load-adapted orientation of the vascular bundles and their fibre caps as the mechanically relevant tissue in branch-stem-attachments of Dracaena marginata. The complex three-dimensional deformations that occur during mechanical loading can be analysed on the basis of quasi-three-dimensional data representations of the outer surface, the inner tissue arrangement (meristem and vascular system), and the course of single vascular bundles within the branch-stem-attachment region. In addition, deformations of vascular bundles could be quantified manually and by using digital image correlation software. This combination of qualitative and quantitative stress and strain analysis leads to an improved understanding of the functional morphology and biomechanics of D. marginata, a plant that is used as a model organism for optimizing branched technical fibre-reinforced lightweight trusses in order to increase their load bearing capacity.
HIPSTR and thousands of lncRNAs are heterogeneously expressed in human embryos, primordial germ cells and stable cell lines
Authors: Yunusov Dinar , Anderson Leticia , DaSilva Lucas Ferreira , Wysocka Joanna , Ezashi Toshihiko , Roberts R. Michael , Verjovski-Almeida Sergio 
Published: September 2016

AbstractEukaryotic genomes are transcribed into numerous regulatory long non-coding RNAs (lncRNAs). Compared to mRNAs, lncRNAs display higher developmental stage-, tissue-, and cell-subtype-specificity of expression, and are generally less abundant in a population of cells. Despite the progress in single-cell-focused research, the origins of low population-level expression of lncRNAs in homogeneous populations of cells are poorly understood. Here, we identify HIPSTR (Heterogeneously expressed from the Intronic Plus Strand of the TFAP2A-locus RNA), a novel lncRNA gene in the developmentally regulated TFAP2A locus. HIPSTR has evolutionarily conserved expression patterns, its promoter is most active in undifferentiated cells, and depletion of HIPSTR in HEK293 and in pluripotent H1BP cells predominantly affects the genes involved in early organismal development and cell differentiation. Most importantly, we find that HIPSTR is specifically induced and heterogeneously expressed in the 8-cell-stage human embryos during the major wave of embryonic genome activation. We systematically explore the phenomenon of cell-to-cell variation of gene expression and link it to low population-level expression of lncRNAs, showing that, similar to HIPSTR, the expression of thousands of lncRNAs is more highly heterogeneous than the expression of mRNAs in the individual, otherwise indistinguishable cells of totipotent human embryos, primordial germ cells, and stable cell lines.
Chondrogenic commitment of human umbilical cord blood-derived mesenchymal stem cells in collagen matrices for cartilage engineering
Authors: Gómez-Leduc Tangni , Hervieu Magalie , Legendre Florence , Bouyoucef Mouloud , Gruchy Nicolas , Poulain Laurent , de Vienne Claire , Herlicoviez Michel , Demoor Magali , Galéra Philippe 
Published: September 2016

AbstractUmbilical cord blood (UCB) is a promising alternative source of mesenchymal stem cells (MSCs), because UCB-MSCs are abundant and harvesting them is a painless non-invasive procedure. Potential clinical applications of UCB-MSCs have been identified, but their ability for chondrogenic differentiation has not yet been fully evaluated. The aim of our work was to characterize and determine the chondrogenic differentiation potential of human UCB-MSCs (hUCB-MSCs) for cartilage tissue engineering using an approach combining 3D culture in type I/III collagen sponges and chondrogenic factors. Our results showed that UCB-MSCs have a high proliferative capacity. These cells differentiated easily into an osteoblast lineage but not into an adipocyte lineage. Furthermore, BMP-2 and TGF-β1 potentiated chondrogenic differentiation, as revealed by a strong increase in mature chondrocyte-specific mRNA (COL2A1, COL2B, ACAN) and protein (type II collagen) markers. Although growth factors increased the transcription of hypertrophic chondrocyte markers such as COL10A1 and MMP13, the cells present in the neo-tissue maintained their phenotype and did not progress to terminal differentiation and mineralization of the extracellular matrix after subcutaneous implantation in nude mice. Our study demonstrates that our culture model has efficient chondrogenic differentiation, and that hUCB-MSCs can be a reliable source for cartilage tissue engineering.
Genome-wide profiling of transfer RNAs and their role as novel prognostic markers for breast cancer
Authors: Krishnan Preethi , Ghosh Sunita , Wang Bo , Heyns Mieke , Li Dongping , Mackey John R. , Kovalchuk Olga , Damaraju Sambasivarao 
Published: September 2016

AbstractTransfer RNAs (tRNAs, key molecules in protein synthesis) have not been investigated as potential prognostic markers in breast cancer (BC), despite early findings of their dysregulation and diagnostic potential. We aim to comprehensively profile tRNAs from breast tissues and to evaluate their role as prognostic markers (Overall Survival, OS and Recurrence Free Survival, RFS). tRNAs were profiled from 11 normal breast and 104 breast tumor tissues using next generation sequencing. We adopted a Case-control (CC) and Case-Only (CO) association study designs. Risk scores constructed from tRNAs were subjected to univariate and multivariate Cox-proportional hazards regression to investigate their prognostic value. Of the 571 tRNAs profiled, 76 were differentially expressed (DE) and three were significant for OS in the CC approach. We identified an additional 11 tRNAs associated with OS and 14 tRNAs as significant for RFS in the CO approach, indicating that CC alone may not capture all discriminatory tRNAs in prognoses. In both the approaches, the risk scores were significant in the multivariate analysis as independent prognostic factors, and patients belonging to high-risk group were associated with poor prognosis. Our results confirmed global up-regulation of tRNAs in BC and identified tRNAs as potential novel prognostic markers for BC.
Holographic intravital microscopy for 2-D and 3-D imaging intact circulating blood cells in microcapillaries of live mice
Authors: Kim Kyoohyun , Choe Kibaek , Park Inwon , Kim Pilhan , Park YongKeun 
Published: September 2016

AbstractIntravital microscopy is an essential tool that reveals behaviours of live cells under conditions close to natural physiological states. So far, although various approaches for imaging cells in vivo have been proposed, most require the use of labelling and also provide only qualitative imaging information. Holographic imaging approach based on measuring the refractive index distributions of cells, however, circumvent these problems and offer quantitative and label-free imaging capability. Here, we demonstrate in vivo two- and three-dimensional holographic imaging of circulating blood cells in intact microcapillaries of live mice. The measured refractive index distributions of blood cells provide morphological and biochemical properties including three-dimensional cell shape, haemoglobin concentration, and haemoglobin contents at the individual cell level. With the present method, alterations in blood flow dynamics in live healthy and sepsis-model mice were also investigated.
Biosynthesis and Regulation of Wheat Amylose and Amylopectin from Proteomic and Phosphoproteomic Characterization of Granule-binding Proteins
Authors: Chen Guan-Xing , Zhou Jian-Wen , Liu Yan-Lin , Lu Xiao-Bing , Han Cai-Xia , Zhang Wen-Ying , Xu Yan-Hao , Yan Yue-Ming 
Published: September 2016

AbstractWaxy starch has an important influence on the qualities of breads. Generally, grain weight and yield in waxy wheat (Triticum aestivum L.) are significantly lower than in bread wheat. In this study, we performed the first proteomic and phosphoproteomic analyses of starch granule-binding proteins by comparing the waxy wheat cultivar Shannong 119 and the bread wheat cultivar Nongda 5181. These results indicate that reduced amylose content does not affect amylopectin synthesis, but it causes significant reduction of total starch biosynthesis, grain size, weight and grain yield. Two-dimensional differential in-gel electrophoresis identified 40 differentially expressed protein (DEP) spots in waxy and non-waxy wheats, which belonged mainly to starch synthase (SS) I, SS IIa and granule-bound SS I. Most DEPs involved in amylopectin synthesis showed a similar expression pattern during grain development, suggesting relatively independent amylose and amylopectin synthesis pathways. Phosphoproteome analysis of starch granule-binding proteins, using TiO2 microcolumns and LC-MS/MS, showed that the total number of phosphoproteins and their phosphorylation levels in ND5181 were significantly higher than in SN119, but proteins controlling amylopectin synthesis had similar phosphorylation levels. Our results revealed the lack of amylose did not affect the expression and phosphorylation of the starch granule-binding proteins involved in amylopectin biosynthesis.
Recloser time–current–voltage characteristic for fuse saving in distribution networks with DG
Authors: Jamali Sadegh , Borhani‐Bahabadi Hossein 
Published: September 2016

Utilities apply a fuse‐saving strategy during auto‐reclosing on transient faults. Integration of distribution generation (DG) into distribution networks (DNs) challenges this strategy as the fault current contribution from the DG may lead to the loss of recloser–fuse coordination. This study proposes a relaying scheme to be applied on microprocessor‐based reclosers for fuse saving under transient fault conditions. A relay operating characteristic is defined which utilises voltage and current magnitudes at the recloser location. The voltage term in the relay characteristic compensates for the reclosing delay resulting from the DG fault contribution. The main features of the relaying scheme are use of local measurements, i.e. no communication link is required, and its independence of number and location of DG. The proposed relaying scheme is validated by simulation study on a practical 20 kV Iranian DN. It is shown that the new scheme maintains proper recloser–fuse coordination for different fault conditions and DG configurations. Moreover, the maximum DG penetration in different locations is obtained whilst the recloser–fuse coordination is upheld. It is shown in a comparative study that the proposed relaying scheme can maintain the coordination for higher DG penetrations than a recent adaptive method reported in the literature.
Positive Oct -3/4 and D2–40 Immunohistochemical Expression in Germ Cells and Suspected Histology Pattern of Intratubular Germ Cell Neoplasia in Boys with Cryptorchidism Vanish after the Age of 2 Years
Authors: Clasen-Linde Erik , Cortes Dina , Thorup Jorgen 
Published: September 2016

Introduction Intratubular germ cell neoplasia (ITGCN) is a precursor to testicular germ cell cancer. Adult germ cell cancer immunohistochemical markers may fail to detect ITGCN in prepubertal boys with congenital cryptorchidism, because positive immunohistochemistry is commonly seen in boys younger than the age of 2 years, where most orchiopexies are performed. The aim of the study was to evaluate the diagnostic challenge to differentiate between a histological pattern of ITGCN and a histological pattern with some atypical germ cells and all positive cancer immunohistochemical markers, but no increased risk of malignancy.
Materials and Methods Histology sections from 373 testicular biopsies from 289 boys aged 1 month to 2 years operated for cryptorchidism were incubated with primary antibodies including anti-placental-like-alkaline phosphatase, antiOct-3/4, anti-C-kit, anti-D2–40, and in case of repeat biopsy with anti-stem cell factor (SCF) receptor.
Results The prevalence of Oct-3/4 and D2–40-positive staining of germ cells in testicular biopsies were in age groups less than 6 months, 100% and 50%; 6–12 months, 60% and 17%; and 1–2 years, 12% and 4%. A 1 year, 1-month-old boy with Prader–Willi syndrome treated with growth hormone had ITGCN in both cryptorchid testes. In another three bilateral nonsyndromic cases, 8 months, 8 months and 1-year-old, a histological pattern in accordance with ITGCN was found. These three boys had a repeat biopsy from both testes performed at the age of 3 years, 4 months, 3.5 years, and 3 years, 10months, respectively. In all cases, the Oct-3/4 and D2–40 positive germ cells turned negative and the histological pattern normalized completely. The primary biopsies had SCF negative germ cells.
Conclusion This study is valuable in identifying the age-related change in Oct-3/4 or D2–40 immunopositive germ cells in seminiferous tubules. An ITGCN-like histological pattern in nonsyndromic cryptorchidism will vanish after the age of 3 years. Even when immunohistochemistry is applied, prepubertal ITGCN is so rarely demonstrated in cryptorchid testes, that it is not plausible that ITGCN generally originates during fetal development in cryptorchidism.
Pericyte–fibroblast transition promotes tumor growth and metastasis
Authors: Hosaka Kayoko , Yang Yunlong , Seki Takahiro , Fischer Carina , Dubey Olivier , Fredlund Erik , Hartman Johan , Religa Piotr , Morikawa Hiromasa , Ishii Yoko , Sasahara Masakiyo , Larsson Ola , Cossu Giulio , Cao Renhai , Lim Sharon , Cao Yihai 
Published: September 2016

Significance
We show that vascular pericytes significantly contribute to cancer invasion and metastasis by the mechanism of the pericyte–fibroblast transition (PFT). This study proposes this concept and indicates the vascular pericyte’s role. Vascular pericytes were considered to remodel tumor vessels toward a mature phenotype. However, once dissociated from tumor vessels their functions within the tumor tissue are not known. In the present study, we show that pericytes, once detached from tumor microvasculatures, underwent differentiation to become stromal fibroblasts, which are known to contribute to tumor invasion and metastasis. Our results show that vascular pericytes are the important source of stromal fibroblasts and targeting PFT may offer a new treatment option in cancer metastasis.
Important role of pedestal ion temperature in the ELM mitigation by supersonic molecular beam injection
Authors: Ma Q. , Yu D.L. , Chen C.Y. , Wei Y.L. , Zhong W.L. , Zou X.L. , Zuo H.Y. , Du J.L. , Liu L. , Dong C.F. , Shi Z.B. , Zhao K.J. , Feng B.B. , Zhou Y. , Wang Z.H. , Xu M. , Liu Yi , Yan L.W. , Yang Q.W. , Yao L.H. , Ding X.T. , Dong J.Q. , Duan X.R. , Liu Yong 
Published: September 2016

Abstract
Edge localized mode (ELM) is successfully mitigated by helium and deuterium supersonic molecular beam injections (SMBIs) on HL-2A. During the ELM mitigation by SMBIs, gradients of ion temperature (T
i) and electron density are softened in the pedestal. It has been observed that the averaged gradient of the T
i decreases around 44% and the well depth of radial electric field (E
r) is reduced by the SMBI during ELM mitigation. Furthermore, at least 20% decrements of T
i have to be attained to achieve a noticeable increase (decrease) of the ELM frequency (amplitude). In addition, the duration of ELM mitigation with helium SMBI is much longer than that with deuterium, likely due to the higher level of recycling neutral gas compared to that of deuterium; in the case of ELM mitigation by helium SMBI, the recovery duration of the density gradient is much shorter (10–20 ms) than that of T
i (up to 40 ms or longer), indicating the importance of the T
i in the ELM mitigation by SMBI. Finally, it has been observed that the T
i is reduced before the beginning of the ELM mitigation, suggesting that the mechanism of the ELM mitigation by SMBI is closely related to the cooling effect.
Conference Report on the 4rd International Symposium on Lithium Applications
Authors: Tabares F.L. , Hirooka Y. , Maingi R. , Mazzitelli G. , Mirnov V. , Nygren R. , Ono M. , Ruzic D.N. 
Published: September 2016

Abstract
The fourth International Symposium on Liquid Metal Application for Fusion Devices (ISLA-2015) was held on 28–30 September 2015 at Granada, Spain, with growing participation and interest from the community working on general aspects of liquid metal research for fusion energy development. The ISLA symposia remain the largest, and arguably, the most important meetings dedicated to liquid metal application for the magnetic fusion research. Overall, 43 presentations plus 7 posters were given, representing 28 institutions from 12 countries. The latest experimental results from 9 magnetic fusion devices were given in 17 presentations from NSTX and LTX (PPPL, USA), FTU (ENEA, Italy), T-11M (Trinity, RF), T-10 (Kurchatov Institute, RF), TJ-II (CIEMAT, Spain), EAST (ASIPP, China), HT-7 (ASIPP, China), DIII-D (GA, USA), ISTTOK (IPFN, Portugal) and KTM (NNC RK, Kazakhstan).
Sessions were devoted to the following: (I) liquid metals (LM) in magnetic confinement experiments (facility overviews), (II) LM in magnetic confinement experiments (topical issues), (III) laboratory experiments, (IV) LM tests in linear plasma devices, (V) LM theory/modeling (VI) LM technology and (VII) a special session on lithium-safety and lithium handling. There were contributions from fusion technology communities including IFMIF and TBM, which provided productive exchanges with physics-oriented magnetic confinement liquid metal research groups. This international workshop will continue on a biennial basis (alternating with the Plasma–Surface Interactions (PSI) Conference), with the next workshop scheduled for Moscow, Russian Federation, in 2017.
OntoBrowser: a collaborative tool for curation of ontologies by subject matter experts
Authors: Ravagli Carlo , Pognan Francois , Marc Philippe 
Published: September 2016

Abstract

Summary
The lack of controlled terminology and ontology usage leads to incomplete search results and poor interoperability between databases. One of the major underlying challenges of data integration is curating data to adhere to controlled terminologies and/or ontologies. Finding subject matter experts with the time and skills required to perform data curation is often problematic. In addition, existing tools are not designed for continuous data integration and collaborative curation. This results in time-consuming curation workflows that often become unsustainable. The primary objective of OntoBrowser is to provide an easy-to-use online collaborative solution for subject matter experts to map reported terms to preferred ontology (or code list) terms and facilitate ontology evolution. Additional features include web service access to data, visualization of ontologies in hierarchical/graph format and a peer review/approval workflow with alerting.

Availability and implementation
The source code is freely available under the Apache v2.0 license. Source code and installation instructions are available at http://opensource.nibr.com. This software is designed to run on a Java EE application server and store data in a relational database.
tHapMix: simulating tumour samples through haplotype mixtures
Authors: Ivakhno Sergii , Colombo Camilla , Tanner Stephen , Tedder Philip , Berri Stefano , Cox Anthony J 
Published: September 2016

Abstract

Motivation
Large-scale rearrangements and copy number changes combined with different modes of clonal evolution create extensive somatic genome diversity, making it difficult to develop versatile and scalable variant calling tools and create well-calibrated benchmarks.

Results
We developed a new simulation framework tHapMix that enables the creation of tumour samples with different ploidy, purity and polyclonality features. It easily scales to simulation of hundreds of somatic genomes, while re-use of real read data preserves noise and biases present in sequencing platforms. We further demonstrate tHapMix utility by creating a simulated set of 140 somatic genomes and showing how it can be used in training and testing of somatic copy number variant calling tools.

Availability and implementation
tHapMix is distributed under an open source license and can be downloaded from https://github.com/Illumina/tHapMix.

Supplementary information
Supplementary data are available at Bioinformatics online.
Vitamin D as Adjunctive Host-Directed Therapy in Tuberculosis: A Systematic Review
Authors: Wallis Robert S. , Zumla Alimuddin 
Published: September 2016

Abstract
Vitamin D plays an important role in innate defenses against intracellular pathogens. Seasonal vitamin D insufficiency (VDI) due to reduced sun exposure far from the equator increases tuberculosis risk. Eight randomized controlled trials examined vitamin D as adjunctive therapy during tuberculosis treatment. The studies varied substantially regarding patient genetic backgrounds, the extent of baseline VDI, the administered dose, the study endpoints, and the quality of the reported data. One carefully performed study in which moderately large vitamin D doses were given to markedly VDI patients found a benefit sufficient to support shortening treatment from 6 to 4 months, although other similar studies did not. Vitamin D is thought to have anti-inflammatory effects. However, 2 studies reported 3 vitamin D recipients with severe paradoxical inflammatory reactions. Future studies of vitamin D in tuberculosis in patients with specific genetic backgrounds must monitor these events closely to determine their risks and underlying mechanisms.