bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinome and mRNA expression profiling of high-grade osteosarcoma cell lines implies Akt signaling as possible target for therapy
Authors: Kuijjer Marieke L , van den Akker Brendy EWM , Hilhorst Riet , Mommersteeg Monique , Buddingh Emilie P , Serra Massimo , Bürger Horst , Hogendoorn Pancras CW , Cleton-Jansen Anne-Marie 
Published: January 2014

AbstractBackgroundHigh-grade osteosarcoma is a primary malignant bone tumor mostly occurring in adolescents and young adults, with a second peak at middle age. Overall survival is approximately 60%, and has not significantly increased since the introduction of neoadjuvant chemotherapy in the 1970s. The genomic profile of high-grade osteosarcoma is complex and heterogeneous. Integration of different types of genome-wide data may be advantageous in extracting relevant information from the large number of aberrations detected in this tumor.MethodsWe analyzed genome-wide gene expression data of osteosarcoma cell lines and integrated these data with a kinome screen. Data were analyzed in statistical language R, usingLIMMAfor detection of differential expression/phosphorylation. We subsequently used Ingenuity Pathways Analysis to determine deregulated pathways in both data types.ResultsGene set enrichment indicated that pathways important in genomic stability are highly deregulated in these tumors, with many genes showing upregulation, which could be used as a prognostic marker, and with kinases phosphorylating peptides in these pathways. Akt and AMPK signaling were identified as active and inactive, respectively. As these pathways have an opposite role on mTORC1 signaling, we set out to inhibit Akt kinases with the allosteric Akt inhibitor MK-2206. This resulted in inhibition of proliferation of osteosarcoma cell lines U-2 OS and HOS, but not of 143B, which harbors aKRASoncogenic transformation.ConclusionsWe identified both overexpression and hyperphosphorylation in pathways playing a role in genomic stability. Kinome profiling identified active Akt signaling, which could inhibit proliferation in 2/3 osteosarcoma cell lines. Inhibition of PI3K/Akt/mTORC1 signaling may be effective in osteosarcoma, but further studies are required to determine whether this pathway is active in a substantial subgroup of this heterogeneous tumor.
Intra-articular hyaluronic acid injection versus oral non-steroidal anti-inflammatory drug for the treatment of knee osteoarthritis: a multi-center, randomized, open-label, non-inferiority trial
Authors: Ishijima Muneaki , Nakamura Toshitaka , Shimizu Katsuji , Hayashi Kunihiko , Kikuchi Hiraku , Soen Satoshi , Omori Go , Yamashita Toshihiko , Uchio Yuji , Chiba Junji , Ideno Yuki , Kubota Mitsuaki , Kurosawa Hisashi , Kaneko Kazuo ,   for the Research Group of Cartilage Metabolism
Published: January 2014

Abstract
Introduction
While many of the commonly used conservative treatments for knee osteoarthritis (OA) have been recognized to be effective, there is still insufficient evidence available. Among the pharmacological treatments for knee OA, oral non-steroidal anti-inflammatory drugs (NSAIDs) act rapidly and are recommended for the management of OA. However, frequent and serious adverse effects of NSAIDs have been recognized. Intra-articular injections of hyaluronic acid (IA-HA) for the treatment of knee OA have been shown to reduce pain and improve joint function. However, there has been no qualified direct comparison study of the efficacy and safety between IA-HA and NSAIDs for patients with knee OA. The aim of this study was to clarify the efficacy and safety of early-phase IA-HA in comparison to those of NSAIDs for patients with knee OA.

Methods
This multicenter, randomized, open-label, parallel-group, non-inferiority comparison study with an oral NSAID involved a total of 200 patients with knee OA. An independent, computer-generated randomization sequence was used to randomly assign patients in a 1:1 ratio to NSAIDs three times per day for five weeks (n = 100) or IA-HA once a week for five weeks (n = 100). The primary endpoint was the percentage change in the patient-oriented outcome measure for knee OA, the Japanese Knee Osteoarthritis Measure (JKOM) score. All patients were questioned regarding any adverse events during treatment. The full analysis set (FAS) was used for analysis. The margin of non-inferiority was 10%.

Results
The analyses of primary endpoint included 98 patients in the IA-HA group and 86 patients in the NSAID group. The difference in the percentage changes of the JKOM score between the two intervention arms (IA-HA; -34.7% (P<0.001), NSAID; -32.2% (P<0.001)) was -2.5% (95% confidence interval (CI): -14.0 to 9.1), indicating IA-HA was not inferior to NSAID. The frequency of both withdrawal and adverse events in the IA-HA group were significantly lower than those in the NSAID group (P = 0.026 and 0.004, respectively).

Conclusions
The early efficacy of IA-HA is suggested to be not inferior to that of NSAIDs, and that the safety of the early phase of IA-HA is superior to that of NSAIDs for patients with knee OA.

Trial registration
UMIN Clinical Trials Registry (UMIN- CTR), UMIN000001026.
Phosphorylated p-70S6K predicts tamoxifen resistance in postmenopausal breast cancer patients randomized between adjuvant tamoxifen versus no systemic treatment
Authors: Beelen Karin , Opdam Mark , Severson Tesa M , Koornstra Rutger HT , Vincent Andrew D , Wesseling Jelle , Muris Jettie J , Berns Els MJJ , Vermorken Jan B , van Diest Paul J , Linn Sabine C 
Published: January 2014

Abstract
Introduction
Activation of the phosphatidylinositol-3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) pathways results in anti-estrogen resistance in vitro, but a biomarker with clinical validity to predict intrinsic resistance has not been identified. In metastatic breast cancer patients with previous exposure to endocrine therapy, the addition of a mammalian target of rapamycine (mTOR) inhibitor has been shown to be beneficial. Whether or not patients on adjuvant endocrine treatment might benefit from these drugs is currently unclear. A biomarker that predicts intrinsic resistance could potentially be used as companion diagnostic in this setting. We tested the clinical validity of different downstream-activated proteins in the PI3K and/or MAPK pathways to predict intrinsic tamoxifen resistance in postmenopausal primary breast cancer patients.

Methods
We recollected primary tumor tissue from patients who participated in a randomized trial of adjuvant tamoxifen (1–3 years) versus observation. After constructing a tissue micro-array, cores from 563 estrogen receptor α positive were immunostained for p-AKT(Thr308), p-AKT(Ser473), p-mTOR, p-p706SK and p-ERK1/2. Cox proportional hazard models for recurrence free interval were used to assess hazard ratios and interactions between these markers and tamoxifen treatment efficacy.

Results
Interactions were identified between tamoxifen and p-AKT(Thr308), p-mTOR, p-p70S6K and p-ERK1/2. Applying a conservative level of significance, p-p70S6K remained significantly associated with tamoxifen resistance. Patients with p-p70S6K negative tumors derived significant benefit from tamoxifen (HR 0.24, P < 0.0001), while patients whose tumor did express p-p70S6K did not (HR = 1.02, P =0.95), P for interaction 0.004. In systemically untreated breast cancer patients, p-p70S6K was associated with a decreased risk for recurrence.

Conclusions
Patients whose tumor expresses p-p70S6K, as a marker of downstream PI3K and/or MAPK pathway activation, have a favorable prognosis, but do not benefit from adjuvant tamoxifen. A potential benefit from inhibitors of the PI3K/Akt/mTOR pathway in these patients needs to be further explored.
Mechanical ventilation during extracorporeal membrane oxygenation
Authors: Schmidt Matthieu , Pellegrino Vincent , Combes Alain , Scheinkestel Carlos , Cooper D Jamie , Hodgson Carol 
Published: January 2014

AbstractThe timing of extracorporeal membrane oxygenation (ECMO) initiation and its outcome in the management of respiratory and cardiac failure have received considerable attention, but very little attention has been given to mechanical ventilation during ECMO. Mechanical ventilation settings in non-ECMO studies have been shown to have an effect on survival and may also have contributed to a treatment effect in ECMO trials. Protective lung ventilation strategies established for non-ECMO-supported respiratory failure patients may not be optimal for more severe forms of respiratory failure requiring ECMO support. The influence of positive end-expiratory pressure on the reduction of the left ventricular compliance may be a matter of concern for patients receiving ECMO support for cardiac failure. The objectives of this review were to describe potential mechanisms for lung injury during ECMO for respiratory or cardiac failure, to assess the possible benefits from the use of ultra-protective lung ventilation strategies and to review published guidelines and expert opinions available on mechanical ventilation-specific management of patients requiring ECMO, including mode and ventilator settings. Articles were identified through a detailed search of PubMed, Ovid, Cochrane databases and Google Scholar. Additional references were retrieved from the selected studies. Growing evidence suggests that mechanical ventilation settings are important in ECMO patients to minimize further lung damage and improve outcomes. An ultra-protective ventilation strategy may be optimal for mechanical ventilation during ECMO for respiratory failure. The effects of airway pressure on right and left ventricular afterload should be considered during venoarterial ECMO support of cardiac failure. Future studies are needed to better understand the potential impact of invasive mechanical ventilation modes and settings on outcomes.
CapR: revealing structural specificities of RNA-binding protein target recognition using CLIP-seq data
Authors: Fukunaga Tsukasa , Ozaki Haruka , Terai Goro , Asai Kiyoshi , Iwasaki Wataru , Kiryu Hisanori 
Published: January 2014

AbstractRNA-binding proteins (RBPs) bind to their target RNA molecules by recognizing specific RNA sequences and structural contexts. The development of CLIP-seq and related protocols has made it possible to exhaustively identify RNA fragments that bind to RBPs. However, no efficient bioinformatics method exists to reveal the structural specificities of RBP–RNA interactions using these data. We present CapR, an efficient algorithm that calculates the probability that each RNA base position is located within each secondary structural context. Using CapR, we demonstrate that several RBPs bind to their target RNA molecules under specific structural contexts. CapR is available at https://sites.google.com/site/fukunagatsu/software/capr.
Ranking the quality of protein structure models using sidechain based network properties
Authors: Ghosh Soma , Vishveshwara Saraswathi 
Published: January 2014

Determining the correct structure of a protein given its sequence still remains an arduous task with many researchers working towards this goal. Most structure prediction methodologies result in the generation of a large number of probable candidates with the final challenge being to select the best amongst these. In this work, we have used Protein Structure Networks of native and modeled proteins in combination with Support Vector Machines to estimate the quality of a protein structure model and finally to provide ranks for these models. Model ranking is performed using regression analysis and helps in model selection from a group of many similar and good quality structures. Our results show that structures with a rank greater than 16 exhibit native protein-like properties while those below 10 are non-native like. The tool is also made available as a web-server(http://vishgraph.mbu.iisc.ernet.in/GraProStr/native_non_native_ranking.html), where, 5 modelled structures can be evaluated at a given time.
Management, Leadership, and User Control in Self-Advocacy: An English Case Study
Authors: Tilley Elizabeth 
Published: January 2014

AbstractThis paper presents findings from a qualitative research project on an English self-advocacy organization. In light of recent political and economic developments that have threatened the sustainability of a number of self-advocacy groups for people with intellectual disability, I seek to explore how one particular organization managed to survive and grow. In particular, the paper explores themes of management, leadership, and user control, linking these to external perceptions about self-advocacy organizations. The organization in my study developed an “interdependent” governance model based on key organizational roles for nondisabled advisors and self-advocates, which proved popular with external funders. Despite the organization's notable achievements, its success raises questions for the wider self-advocacy movement, notably how leadership capacity can be developed among self-advocates.
White-black graphs and right-angled hyperbolic handlebodies
Authors: Ma Jiming 
Published: January 2014

Abstract
We prove a partial analog of Andreev’s theorem on compact hyperbolic polyhedra for irreducible, atoroidal, compact 3-manifolds with non-empty boundary. More precisely, for a 3-manifoldM with non-empty boundary, let Γ be a so called white-black graph in ᏮM; we characterize the conditions on Γ such that M admits a compact hyperbolic structure with Γ as the singular locus which is right-angled on each edge of Γ. In particular, our result applies to handlebodies.
Ein stochastischer Algorithmus zur Bildgenerierung
durch einen zweidimensionalen
Markoff-Erneuerungsprozess
Authors: Dubinin Dmitry , Geringer Viktor , Kochegurov Alexander , Reif Konrad 
Published: January 2014

Zusammenfassung
In diesem Beitrag wird ein stochastischer Algorithmus zur
Bildgenerierung durch einen zweidimensionalen Markov Renewal
Process (MRP) betrachtet. Die Zustandsraumauswahl und
Gittereigenschaften, die die Gitterform (eine Form der
Konturstruktur) voraussetzt, werden manuell in Voraus vom Operator
bestimmt. Der Algorithmus lässt verschiedene Typen der
Gitterformstrukturen zu. Horizontale, senkrechte und diagonale
Elemente bei einer 8-fach-Nachbarschaft sind erlaubt. Er bietet
eine hervorragende Grundlage für Entwurf, Analyse, Validierung und
Qualitätssicherung von Bildverarbeitungsalgorithmen.
Why Do Some People Dislike Conceptual Metaphor Theory?
Authors: Gibbs Raymond W. 
Published: January 2014

Abstract
Conceptual metaphor theory (CAIT) is the dominant force in the contemporary world of interdisciplinary metaphor studies. Over the past thirty years, scholars working within the CMT framework have gathered an impressive body of empirical research using a variety of linguistic, psychological, and computational modeling methods drat supports key parts of the theory However, CMT has also been widely been criticized - both as a theory of metaphor use and for its claims about the embodied, metaphorical character of abstract thought. This article describes some of die reasons people dislike CMT and suggests ways that CMT scholars may alter some people’s misunderstandings and address their legitimate concerns about the theory.
Do Metaphors Evolve? The Case of the Social Organism
Authors: Mouton Nico 
Published: January 2014

Abstract
A long line of philosophers and social scientists have defended and extended the curious idea that collective entities - states and societies, cities and corporations - are biological organisms. In this article, I study a few short but spectacular episodes from the history of that metaphor, juxtapose mappings made in one era with correspondences conjured in other epochs, and reflect upon the reasons why they differ. By adopting a historical perspective on the process whereby the notion of a ‘social organism’ evolved from its relatively simple beginnings in ancient philosophy to its rather complex manifestations in the modern social sciences, I hope to show that there are good reasons to reconsider both Lakoff’s decree that metaphors ‘should not be thought of as processes’ and his declaration that they should instead be seen as consisting of ‘a fixed pattern of ontological correspondences across domains’ (Lakoff, 1993:210, emphasis
added). Building on ideas about metaphor that emerged during the Nineteenth Century, I argue that what may initially appear to be a fixed pattern of projections is often better understood as a temporary station in a fluid process.
Metaphor and the Communicative Mind
Authors: Brandt Line 
Published: January 2014

Abstract
On the occasion of the thirtieth anniversary of the first cognitive-semantic theory of metaphor - Metaphors
We Live By (1980) - this paper presents a communication-oriented perspective on the practice of metaphor analysis. Through discussion of contemporary metaphor theories, it identifies a number of unresolved issues. Among these are the notions of domains, mental spaces and binding, the unidirectionality hypothesis, the emergence problem, the significance of pragmatic context, and the philosophical status of representations. The theories discussed are conceptual metaphor theory, conceptual integration theory, the neural theory of language, the attribution model of metaphor, semiotic integration theory, and relevance theoretic approaches to metaphor including the hybrid theory of metaphor. Comparing analyses and explanatory frameworks, the paper offers a theoretical and methodological critique of these approaches - as food for thought and fuel for prospective future research projects in cognitive linguistics and beyond.
Are Cross-Domain Mappings Psychologically Deep, but Conceptually Shallow? What is Still Left to Test for Conceptual Metaphor Theory
Authors: Bundgaard Peer F. 
Published: January 2014

Abstract
This article assesses two objections directed at Conceptual Metaphor Theory: (1) it is circular in that it only provides linguistic evidence for the psychological reality of cross-domain mappings, intended to explain the empirical reality of metaphorical expressions in language; (2) it does not support the conclusion that the massive existence of metaphorical expressions in language reflects the metaphorical structuring of abstract concepts. It is my aim to disentangle these objections. Evidence abounds that makes the first objection obsolete, proving the psychological reality of cross-domain mappings. However, this does not imply that abstract concepts are metaphorically structured: experiments that prove objection (1) wrong cannot be invoked to reject objection (2). Some even tend to justify it.
Synthesis and biocidal activity of novel N-halamine hydantoin-containing polystyrenes
Authors: Chylińska Marta , Ziegler-Borowska Marta , Kaczmarek Halina , Burkowska Aleksandra , Walczak Maciej , Kosobucki Przemysław 
Published: January 2014

AbstractThree homopolymers containing hydantoin substituents were obtained by chemical modification of reactive p-chloromethylated polystyrene. The prepared polymers were chlorinated to yield N-halamine materials with biocidal properties. The chemical structure of polymers was characterized by Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. All of the hydantoin polymers are insoluble in water and common organic solvents. Microbiological investigations prove the high biocidal activity of the obtained chlorinated polystyrene derivatives containing spirohydantoin moieties. The obtained polymers will be useful in designing and constructing medical and pharmaceutical equipment. The ability to crosslink allows to expect easy grafting of these biocidal macrochains, for example, on textiles.
Synthesis and characterization of poly(vinyl chloride-graft-2-vinylpyridine) graft copolymers using a novel macroinitiator by reversible addition-fragmentation chain transfer polymerization
Authors: Öztürk Temel , Göktaş Melahat , Savaş Bedrettin , Işıklar Mustafa , Atalar Mehmet Nuri , Hazer Baki 
Published: January 2014

AbstractSynthesis of poly(vinyl chloride-graft-2-vinylpyridine) graft copolymers was carried out by reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-vinylpyridine using a novel macroinitiator (RAFT macroinitiator). For this purpose, RAFT macroinitiator was obtained from the potassium salt of ethyl xanthogenate and poly(vinyl chloride) (PVC). Then the graft copolymers were synthesized by using RAFT macroinitiator and 2-vinylpyridine. The principal parameters such as monomer concentration, initiator concentration, and polymerization time that affect the polymerization reaction were studied. The effect of the reaction conditions on the heterogeneity index and molecular weight was also investigated. The block lengths of the graft copolymers were calculated by using 1H nuclear magnetic resonance (1H NMR) spectra. The block lengths of the copolymers could be adjusted by varying the monomer and initiator concentrations. The characterizations of the samples were carried out by using 1H NMR, Fourier-transform infrared spectroscopy, gel-permeation chromatography, thermogravimetric analysis, differential scanning calorimetry, and fractional precipitation (γ value) techniques. RAFT polymerization is used to control the polymerization of 2-vinylpyridine over a broad range of molecular weights.
Size and diffusion of polymer in media filled with periodic fillers
Authors: Li Chao-Yang , Zhang Shuang , Huang Jian-Hua , Luo Meng-Bo 
Published: January 2014

AbstractThe effect of nanosized fillers on the equilibrium and dynamic properties of a single polymer chain has been studied by using off-lattice Monte Carlo (MC) simulation. Fillers of identical size are arranged periodically in the system and the Lennard-Jones (LJ) interaction is considered between the polymer and fillers. Our results show that the statistical size and dynamic diffusion properties of the polymer are not only dependent on the size of the polymer relative to the size of fillers and the distance between fillers, but also dependent on the interaction between the polymer and filler. The statistical size of the polymer can increase or decrease. Normal diffusion is always observed for long polymers and small fillers, whereas a transition from a desorbed state to an adsorbed state is observed for short polymers and large fillers. Finally, the size and diffusion of the polymer on an infinitely large surface are studied for comparison.
Impact of aspect ratio and CNT loading on the dynamic mechanical and flammability properties of polyethylene nanocomposites
Authors: Thomas Selvin P. , Rahaman Mostafizur , Hussein Ibnelwaleed A. 
Published: January 2014

AbstractIn this study, the effects of aspect ratio and loading of multiwalled carbon nanotubes (MWCNTs) on the dynamic mechanical, thermal, and flammability properties of low-density polyethylene (LDPE)/MWCNT nanocomposites prepared by the melt blending technique were investigated. At low CNT loading, CNT with low aspect ratio acted as a plasticizer in LDPE. The storage modulus of the nanocomposites increased with the increase in aspect ratio and CNT loading. The increase in scan rate for the composites results in the decrease in total crystallinity, crystallization peak temperature, and a late onset of crystallization. The flammability properties like heat release capacity, peak heat release rate, and total heat release decrease with the increase in both aspect ratio and loading of CNTs in the composites.