bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acquired Resistance to EGFR Inhibitors Is Associated with a Manifestation of Stem Cell–like Properties in Cancer Cells
Authors: Shien Kazuhiko , Toyooka Shinichi , Yamamoto Hiromasa , Soh Junichi , Jida Masaru , Thu Kelsie L. , Hashida Shinsuke , Maki Yuho , Ichihara Eiki , Asano Hiroaki , Tsukuda Kazunori , Takigawa Nagio , Kiura Katsuyuki , Gazdar Adi F. , Lam Wan L. , Miyoshi Shinichiro 
Published: March 2013

Abstract
Acquired resistance to EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) is a critical problem in the treatment of lung cancer. Although several mechanisms have been shown to be responsible for acquired resistance, all mechanisms have not been uncovered. In this study, we investigated the molecular and cellular profiles of the acquired resistant cells to EGFR-TKI in EGFR-mutant lung cancers. Four EGFR-mutant cell lines were exposed to gefitinib by stepwise escalation and high-concentration exposure methods, and resistant sublines to gefitinib were established. The molecular profiles and cellular phenotypes of these resistant sublines were characterized. Although previously reported, alterations including secondary EGFR T790M mutation, MET amplification, and appearance of epithelial-to-mesenchymal transition (EMT) features were observed, these 2 drug-exposure methods revealed different resistance mechanisms. The resistant cells with EMT features exhibited downregulation of miRNA-200c by DNA methylation. Furthermore, the HCC827-derived subline characterized by the high-concentration exposure method exhibited not only EMT features but also stem cell–like properties, including aldehyde dehydrogenase isoform 1 (ALDH1A1) overexpression, increase of side-population, and self-renewal capability. Resistant sublines with stem cell–like properties were resistant to conventional chemotherapeutic agents but equally sensitive to histone deacetylase and proteasome inhibitors, compared with their parental cells. ALDH1A1 was upregulated in clinical samples with acquired resistance to gefitinib. In conclusion, our study indicates that the manner of EGFR-TKI exposure influences the mechanism of acquired resistance and the appearance of stem cell–like property with EGFR-TKI treatment. Cancer Res; 73(10); 3051–61. ©2013 AACR.
Gossypin as a Novel Selective Dual Inhibitor of v-raf Murine Sarcoma Viral Oncogene Homolog B1 and Cyclin-Dependent Kinase 4 for Melanoma
Authors: Bhaskaran Shylesh , Dileep Kalarikkal V. , Deepa Sathyaseelan S. , Sadasivan Chittalakkottu , Klausner Mitch , Krishnegowda Naveen K. , Tekmal Rajeshwar R. , VandeBerg John L. , Nair Hareesh B. 
Published: March 2013

Abstract
Mutation in the BRAF gene (BRAFV600E) exists in nearly 70% of human melanomas. Targeted therapy against BRAFV600E kinase using a recently identified RAF-selective inhibitor, PLX4032, has been successful in early clinical trials. However, in patients with the normal BRAF allele (wild-type), PLX4032 is protumorigenic. This conundrum identifies the unmet need for novel therapeutic agents to target BRAFV600E kinase that are not counterproductive. We have identified gossypin, a pentahydroxy flavone, as a potent antimelanoma agent. Gossypin inhibited human melanoma cell proliferation, in vitro, in melanoma cell lines that harbor both BRAFV600E kinase and cyclin-dependent kinase 4 (CDK4) as well as in cells with BRAF wild-type allele. Gossypin inhibited kinase activities of BRAFV600E and CDK4, in vitro, possibly through direct binding of gossypin with these kinases, as confirmed by molecular docking studies. For cells harboring the BRAFV600E, gossypin inhibited cell proliferation through abrogation of the MEK–ERK–cyclin D1 pathway and in cells with BRAF wild-type allele, through attenuation of the retinoblastoma–cyclin D1 pathway. Furthermore, gossypin significantly inhibited melanoma growth in an organotypic three-dimensional skin culture mimicking human skin. Gossypin (10 and 100 mg/kg) treatment for 10 days in human melanoma (A375) cell xenograft tumors harboring BRAFV600E significantly reduced tumor volume through induction of apoptosis and increased survival rate in mice, and the effect was significantly superior to that of PLX4032 (10 mg/kg) or roscovitine 10 mg/kg. In summary, this study identified gossypin as a novel agent with dual inhibitory effects for BRAFV600E kinase and CDK4 for treatment of melanoma. Mol Cancer Ther; 12(4); 361–72. ©2013 AACR.
Combination of Intermittent Calorie Restriction and Eicosapentaenoic Acid for Inhibition of Mammary Tumors
Authors: Mizuno Nancy K. , Rogozina Olga P. , Seppanen Christine M. , Liao D. Joshua , Cleary Margot P. , Grossmann Michael E. 
Published: April 2013

Abstract
There are a number of dietary interventions capable of inhibiting mammary tumorigenesis; however, the effectiveness of dietary combinations is largely unexplored. Here, we combined 2 interventions previously shown individually to inhibit mammary tumor development. The first was the use of the omega-3 fatty acid, eicosapentaenoic acid (EPA), and the second was the implementation of calorie restriction. MMTV-Her2/neu mice were used as a model for human breast cancers, which overexpress Her2/neu. Six groups of mice were enrolled. Half were fed a control (Con) diet with 10.1% fat calories from soy oil, whereas the other half consumed a diet with 72% fat calories from EPA. Within each diet, mice were further divided into ad libitum (AL), chronic calorie-restricted (CCR), or intermittent calorie-restricted (ICR) groups. Mammary tumor incidence was lowest in ICR-EPA (15%) and highest in AL-Con mice (87%), whereas AL-EPA, CCR-Con, CCR-EPA, and ICR-Con groups had mammary tumor incidence rates of 63%, 47%, 40%, and 59%, respectively. Survival was effected similarly by the interventions. Consumption of EPA dramatically reduced serum leptin (P &lt; 0.02) and increased serum adiponectin in the AL-EPA mice compared with AL-Con mice (P &lt; 0.001). Both CCR and ICR decreased serum leptin and insulin-like growth factor I (IGF-I) compared with AL mice but not compared with each other. These results illustrate that mammary tumor inhibition is significantly increased when ICR and EPA are combined as compared with either intervention alone. This response may be related to alterations in the balance of serum growth factors and adipokines. Cancer Prev Res; 6(6); 540–7. ©2013 AACR.
Towards Historicizing “Magic” in Antiquity
Authors: Otto Bernd-Christian 
Published: March 2013

Abstract
Even though the concept of “magic” has suffered severe criticism in academic discourse, the category continues to be used in many disciplines. During the last two decades, classicists in particular have engaged in a lively discussion over “magic” and have produced an impressive amount of written output. Given the impossibility of defining “magic” in a consistent and widely accepted manner, one cannot help but wonder what these scholars are actually talking about. Hence this paper purports (a) to critically review the recent debate on “magic” in Classical Studies, (b) to advocate for abandoning an abstract category of “magic” in favour of a proper analysis of ancient sources and (c) to historicize the term “magic” in Antiquity, that is, to muse on its ancient semantics, functions, and contexts. This methodological approach does not only overcome the major problems inherent in modern definitions of “magic,” but will also yield new insights into terminologies, modes of thought and speech strategies that underlie ancient religious discourses.
Regarding Rocky: A Theoretical and Ethnographic Exploration of Interspecies Intersubjectivity
Authors: Young Robert L. 
Published: March 2013

Abstract
Both theoretical and empirical work in a variety of disciplines has resulted in a recent turn away from Cartesian and Meadian anthropocentrism in the direction of a radical reconsideration of nonhuman animal mind and agency. Central to sociology’s role in envisioning a repopulated social world is the analysis of nonhuman-human social interaction. Because all social action is predicated on certain assumptions regarding the minds of others, a theory of intersubjectivity must be at the core of any such project. It is argued here that the key elements employed in Alfred Schutz’s conceptualization of intersubjectivity among humans are also demonstrated in the routine communicative projects of humans and their companion animals. After presenting a Schutzian theory of intersubjectivity, this article analyzes, from an ethnographic perspective, elements of the everyday lifeworld Rocky—a deaf, paraplegic cat—cohabits with the author and other family members. Through that analysis, the paper demonstrates that the dynamics of everyday interactions through which Rocky actively participates in the creation of meaning and the achievement of understanding is highly consistent with Schutz’s theory of human intersubjectivity.
The Metaphor at Stake in Ezra 9:8
Authors: Moffat Donald P. 
Published: March 2013

Abstract
This article argues that the tendency to interpret the stake metaphor in Ezra 9:8 as a reference to security is out of step with the sentiments of the penitential prayer in which it is used. The prayer emphasizes community vulnerability. Other uses of the stake as a metaphor in the Hebrew Bible include an element of divine dependence either explicitly or implicitly. The metaphor is precisely in tune with the sentiments of the prayer and represents Yahweh-dependent support. Interpretations need to reflect the nuances of the metaphor while translations must be careful not to obscure its subtleties.
The Syntax of the Periphrastic Progressive in the Septuagint and the New Testament
Authors: Bentein Klaas 
Published: March 2013

Abstract
In this article, I discuss the use of the periphrastic progressive construction of εἰµί with present participle in the Septuagint and the New Testament. I argue that a broad distinction can be made between two main uses, called “durative progressive” and “focalized progressive.” In both cases, a number of syntactic frames can be specified in which the periphrastic construction occurs. I conclude the article by discussing the relationship between the Septuagintal and the New Testamental use of the periphrastic construction, arguing that while there are many similarities, this relationship should not be conceived of in terms of imitation, as some scholars have suggested.
Finding the Edges of Payday Lending
Authors: Aitken Rob 
Published: March 2013

Abstract
Although virtually unknown in 1990, payday lending has become an important and profitable credit practice over the past two decades. Because of this growth, and because it has been implicated in ever-increasing levels of debt among the poor, payday lending has been confronted by an active political movement which has had some success in imposing forms of regulation in the United States and abroad. This paper argues, however, that this activism has failed to address the increasingly globalized nature of payday lending. Over the past five years, in particular, payday lending has become a thoroughly globalized practice deeply connected to and enabled by liberalized global financial markets. This paper reflects on the distance between the activism that now confronts it in national or subnational contexts and this increasingly global reach of payday lending. It concludes by making the case for a more fully globalized conception of global financial justice.
Frustrating Noble Intentions
Authors: Pohrib Aurelia Marina 
Published: March 2013

Abstract
This article will show that the International Criminal Court (ICC) prosecutorial strategy may hamper any deterrent effect created by the Court, by analyzing the flaws of the prosecutorial strategy as it relates to the ICC’s possibility of deterring future violations. The deterrence goal of the ICC and the Prosecutor’s “policy of focused investigations and prosecutions” on those “who bear the greatest responsibility” do not “constitute a harmonious whole; rather, they pull in different directions, diminishing each other’s power and creating tensions.”
The Sempra Annulment Decision of 29 June 2010 and Subsequent Developments in Investment Arbitration Dealing with the Necessity Defence
Authors: Cristani Federica 
Published: March 2013

Abstract
On 29 June 2010, an ad hoc International Centre for Settlement of Investment Disputes (ICSID) Annulment Committee annulled the 2007 Sempra Award for manifest excess of powers (within the meaning of the ICSID Convention), as it found that the Tribunal had failed to apply the correct law. The decision took into account the measures adopted by the Argentine Government to face the 2001 economic and political crisis and (like other previous awards and decisions on similar cases) raised the issue of the interpretation and application of the necessity defence in situations of economic emergencies. The approach of the ad hoc Committee on this particular point is the main focus of this note.
Sis Replacement on Live Processes
Authors: Timms Clive 
Published: April 2013

The increasing demand for oil and gas before the global recession was driving up prices and the focus of oil and gas producers was to maintain and maximise production from every available facility. Older unreliable facilities were being rapidly upgraded including the replacement of Safety Instrumented Systems (SIS) such as emergency shutdown (ESD) systems, process shutdown (PSD) systems, Emergency Depressurisation (EDP) systems and fire and gas (F&G) systems. Traditionally, the replacement of such safety critical systems is undertaken during a plant shutdown opportunity to ensure that process integrity is maintained and to facilitate comprehensive commissioning and validation without the presence of the process hazards. However, in the era of high oil and gas demand we saw more and more SIS replacement projects being undertaken whilst the process was still fully operational, even though this potentially compromised the integrity of a facility. Oil and gas are finite resources and high prices will inevitably return. This paper summarises the findings of a number of IEC 61508 and IEC 61511 compliance audits undertaken for SIS replacement projects on live production facilities.
Data Driven Prognosis and Health Maintenance for Complex Industrial Processes with Production Optimization and Energy Savings
Authors: Wang A. P. , Wang H. , Guo L. , Zhang K. J. 
Published: April 2013

Prognosis and Health Management (PHM) is an increasingly important area of research in the past few years. This is due to the requirement on economical health management for complex industrial processes that consists of a large number of units and equipment which operate together in order to fulfill their production requirement in terms of guaranteed product quality, improved production efficiency and reduced energy cost. This paper reviews some aspects on PHM and discusses possible future directions. In particular, three new areas of research are pointed out, namely the stochastic distribution control based active PHM, the passivity analysis based PHM and the multiple data driven based models PHM. The key feature of these novel PHM strategies is that they can link the remaining useful life (RUL) estimation with decision variables such as control loop set points in the complex industrial processes. Such a link forms a group of models by which pro-active PHM strategies can be implemented in practice.
Is there a cure for systemic lupus erythematosus?
Authors: Rosario C , Seguro L , Vasconcelos C , Shoenfeld Y 
Published: April 2013

The morbidity and mortality of systemic lupus erythematosus (SLE) is a subject of intense relevance in the literature, yet descriptions of prolonged and sustained remissions or even cure are barely reported. In recent decades the life expectancy in SLE patients has improved, but the quality of life seems to be poor compared with other chronic diseases and with the general population. The immunopathogenesis of SLE is complex and not fully understood, so patients have been treated with nonspecific immunosuppressive therapies. But in recent years, because of advances in basic science, targeted therapies have been developed. Despite the progress made in treating SLE, currently a cure in SLE seems to be a myth. SLE it seems, remains incurable. A specific treatment has not emerged to directly abrogate a disease-specific autoimmune response. Relapsing manifestations and complications of treatment still remain important markers of morbidity.
Parallel evolution of senescence in annual fishes in response to extrinsic mortality
Authors: Terzibasi Tozzini Eva , Dorn Alexander , Ng’oma Enoch , Polačik Matej , Blažek Radim , Reichwald Kathrin , Petzold Andreas , Watters Brian , Reichard Martin , Cellerino Alessandro 
Published: April 2013

Abstract

Background
Early evolutionary theories of aging predict that populations which experience low extrinsic mortality evolve a retarded onset of senescence. Experimental support for this theory in vertebrates is scarce, in part for the difficulty of quantifying extrinsic mortality and its condition- and density-dependent components that –when considered- can lead to predictions markedly different to those of the “classical” theories. Here, we study annual fish of the genus Nothobranchius whose maximum lifespan is dictated by the duration of the water bodies they inhabit. Different populations of annual fish do not experience different strengths of extrinsic mortality throughout their life span, but are subject to differential timing (and predictability) of a sudden habitat cessation. In this respect, our study allows testing how aging evolves in natural environments when populations vary in the prospect of survival, but condition-dependent survival has a limited effect. We use 10 Nothobranchius populations from seasonal pools that differ in their duration to test how this parameter affects longevity and aging in two independent clades of these annual fishes.

Results
We found that replicated populations from a dry region showed markedly shorter captive lifespan than populations from a humid region. Shorter lifespan correlated with accelerated accumulation of lipofuscin (an established age marker) in both clades. Analysis of wild individuals confirmed that fish from drier habitats accumulate lipofuscin faster also under natural conditions. This indicates faster physiological deterioration in shorter-lived populations.

Conclusions
Our data provide a strong quantitative example of how extrinsic mortality can shape evolution of senescence in a vertebrate clade. Nothobranchius is emerging as a genomic model species. The characterization of pairs of closely related species with different longevities should provide a powerful paradigm for the identification of genetic variations responsible for evolution of senescence in natural populations.
Prokaryote-expressed M2e protein improves H9N2 influenza vaccine efficacy and protection against lethal influenza a virus in mice
Authors: Kim Eun-Ha , Lee Jun-Han , Pascua Philippe Noriel Q , Song Min-Suk , Baek Yun-Hee , Kwon Hyeok-il , Park Su-Jin , Lim Gyo-Jin , Decano Arun , Chowdhury Mohammed YE , Seo Su-Kyung , Song Man Ki , Kim Chul-Joong , Choi Young-Ki 
Published: April 2013

AbstractBackgroundInfluenza vaccines are prepared annually based on global epidemiological surveillance data. However, since there is no method by which to predict the influenza strain that will cause the next pandemic, the demand to develop new vaccination strategies with broad cross-reactivity against influenza viruses are clearly important. The ectodomain of the influenza M2 protein (M2e) is an attractive target for developing a vaccine with broad cross-reactivity. For these reasons, we investigated the efficacy of an inactivated H9N2 virus vaccine (a-H9N2) mixed with M2e (1xM2e or 4xM2e) proteins expressed inEscherichia coli, which contains the consensus of sequence the extracellular domain of matrix 2 (M2e) of A/chicken/Vietnam/27262/09 (H5N1) avian influenza virus, and investigated its humoral immune response and cross-protection against influenza A viruses.ResultsMice were intramuscularly immunized with a-H9N2, 1xM2e alone, 4xM2e alone, a-H9N2/1xM2e, or a-H9N2/4xM2e. Three weeks post-vaccination, mice were challenged with lethal homologous (A/ chicken /Korea/ma163/04, H9N2) or heterosubtypic virus (A/Philippines/2/82, H3N2 and A/aquatic bird/Korea/maW81/05, H5N2). Our studies demonstrate that the survival of mice immunized with a-H9N2/1xM2e or with a-H9N2/4xM2e (100% survival) was significantly higher than that of mouse-adapted H9N2 virus-infected mice vaccinated with 1xM2e alone or with 4xM2e alone (0% survival). We also evaluated the protective efficacy of the M2e + vaccine against infection with mouse-adapted H5N2 influenza virus. Protection from death in the control group (0% survival) was similar to that of the 1×M2e alone and 4xM2e alone-vaccinated groups (0% survival). Only 40% of mice vaccinated with vaccine alone survived challenge with H5N2, while the a-H9N2/1×M2e and a-H9N2/4×M2e groups showed 80% and 100% survival following mouse-adapted H5N2 challenge, respectively. We also examined cross-protection against human H3N2 virus and found that the a-H9N2/1×M2e group displayed partial cross-protection against H3N2 (40% survival), whereas vaccine alone, 1×M2e alone, 4×M2e alone, or H9N2/1×M2e groups showed incomplete protection (0% survival) in response to challenge with a lethal dose of human H3N2 virus.ConclusionsTaken together, these results suggest that prokaryote-expressed M2e protein improved inactivated H9N2 virus vaccine efficacy and achieved cross-protection against lethal influenza A virus infection in mice.
Endobronchial endometriosis presenting as central-type lung cancer: a case report
Authors: Yu Juan-Han , Lin Xu-Yong , Wang Liang , Liu Yang , Fan Chui-Feng , Zhang Yong , Wang En-Hua 
Published: April 2013

Abstract

Abstract
A 45-year-old female patient was referred to our hospital for complaining of dyspnea and coughing in the past four months. The computed tomography scanning demonstrated a central lesion in the upper lobe of the left lung close to the hilar, and the subsequent bronchoscopy revealed a polypoid lesion of the distal of the left main bronchus. This patient was diagnosed clinically as “possibly central-type lung cancer”. However, the pathologic result of the surgically excised polypoid lesion was endobronchial endometriosis.

Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1077439085928525
Deposition of suspended fine particulate matter in a library
Authors: Smolík Jiří , Mašková Ludmila , Zíková Naděžda , Ondráčková Lucie , Ondráček Jakub 
Published: April 2013

Abstract
To analyse deposition of fine particulate matter (PM) on book surfaces we put twelve bunches of cellulose filters on a free shelf of the National Library in Prague, exposed them for three, six, nine, and twelve months to indoor air and analysed them after each period by Scanning Electron Microscopy (SEM) and Ion Chromatography (IC). Results showed that fine particles were deposited predominantly on the surface of the top filter but partly also on the surfaces of inner filters. It indicates fine particles penetrated between filters. The penetration and deposition of particles was also modelled as Brownian diffusion between two parallel filters. The model prediction demonstrated that fine particles penetrate between filters, with the depth of penetration limited by parallel diffusional deposition on filter surfaces. This is in qualitative agreement with SEM and IC investigations. The results show that beside the top part fine PM can deposit onto all available surfaces of books.