bluuebunny/crossref_metadata_2025 huggingface dataset:
Agglomeration and simplified housing boom
Authors: Wang An-Ming
Published: March 2015

Both ‘spatial skewness’ in population sizes, incomes and house prices and ‘agglomeration economies’ are important features in many countries. This paper uses a solvable core-periphery model capturing the two features to specify a market-induced housing boom under the condition of a fixed or very inelastic housing supply. Two main insights emerge from our analysis. First, there exists a rising gap of housing rent to income ratio between two regions. Second, the growth rate of housing rents is higher than that of incomes during an endogenous agglomeration process. These results help us to realise that strong housing booms only take place in a few large cities or metropolitan areas stemming from a homogeneous economy.
Spatial mobility and opportunity in Australia: Residential selection and neighbourhood connections
Authors: Clark William , Maas Regan
Published: March 2015

Households choose places from a hierarchy of options defined by social, economic and environmental contexts and these choices are conditioned by economic contexts and family status. While we know a good deal about the choice processes, we know somewhat less about the spatial outcomes of these decisions apart from the well-established finding that most residential changes involve relatively short distances. Recent research has begun to fill that gap and in this paper the research is extended by using data from the survey Household, Income and Labor Dynamics in Australia (HILDA) to construct matrices of socio-spatial movement and consider the relationship of community in-flows and out-flows and the probability moving above and below the diagonal of the matrix. The research shows that there is substantial movement across the matrix of opportunities defined by an Index of Advantage and Disadvantage (Seifa). Economic resources and social status improves an individual’s chance of moving up, as expected, and there is little evidence of polarisation and isolation of the lowest decile communities. It is true that there is substantial within-decile movement but there is also movement away from the diagonal. The analysis suggests that the opportunity matrix is still open in Australia.
Pacifying Babel’s Tower: A scientometric analysis of polycentricity in urban research
Authors: van Meeteren Michiel , Poorthuis Ate , Derudder Ben , Witlox Frank
Published: March 2015

It is sometimes claimed that the degree of polycentricity of an urban region influences that region’s competitiveness. However, because of widespread use and policy relevance, the underlying concept of polycentricity has become a ‘stretched concept’ in urban studies. As a result, academic debate on the topic leads to situations reminiscent of Babel’s Tower. This meta-study of the scientific literature in urban studies traces the conceptual stretching of polycentricity using scientometric methods and content analysis. All published studies that either apply the concept directly or cite a work that does, were collected from the Scopus bibliographic database. This resulted in a citation network with over 9000 works and more than 20,000 citations between them. Network analysis and clustering algorithms were used to define the most influential papers in different citation clusters within the network. Subsequently, we employed content analysis to systematically assess the mechanisms associated with the formation of polycentric urban systems in each of these papers. Based on this meta-analysis, we argue that the common categorisation of polycentricity research in intra-urban, inter-urban and inter-regional polycentricity is somewhat misleading. More apt categorisations to understand the origins of polycentricity’s conceptual ambiguity relate to different methodological traditions and geographical contexts in which the research is conducted. Nonetheless, we observe a firm relation across clusters between assessments of polycentricity and different kinds of agglomeration economies. We conclude by proposing a re-conceptualisation of polycentricity based on explicitly acknowledging the variable spatial impact of these different kinds of agglomeration economies.
Death and the City
Authors: Sloan Kathryn A.
Published: March 2015

Poised on the cusp of the twentieth century, many urban citizens believed their societies to be sickened by suicide epidemics. It was assumed that rapid modernization and technological advance caused some individuals to develop nervous conditions that negated their impulses for self-preservation. Although statistical evidence pointed to higher rates of suicide among adult men, society believed that youth and women were most vulnerable to the epidemic. This article examines cases of young women carefully planning their suicides in symbolic spaces of Mexico City. It argues that public suicides made self-conscious decisions on how they would die, in particular choosing the sites of their deaths for their cultural meanings. How society viewed their deaths depended upon their virtue in life; nevertheless, Mexicans perpetuated their culture of commemorating the dead by erecting ephemeral memorials at the sites of death.
Lung adenocarcinoma with clear cell features producing carbohydrate antigen 19-9
Authors: Goto Taichiro , Hada Masao , Oyama Toshio
Published: March 2015

A 76-year-old man underwent surgery for lung cancer. Histopathologically, most of the resected tumor was composed of polygonal cells with foamy cytoplasm, and the cells were arranged predominantly in acinar patterns. In this case, although the carbohydrate antigen 19-9 level was high before surgery, it normalized after resection. The tumor was considered a carbohydrate antigen 19-9-producing tumor, which was further supported by the results of immunohistochemical analysis. Adenocarcinoma with clear cell features, producing carbohydrate antigen 19-9, is an exceedingly rare entity.
Painting the Nation
Authors: Rodner Victoria L. , Preece Chloe
Published: March 2015

Politics and art have throughout history, intersected in diverse and complex ways. Ideologies and political systems have used the arts to create a certain image and, depending on the form of government this has varied from clear-cut state propaganda, to patronage, to more indirect arms-length funding procedures. Therefore, artists working within the macro-level socio-political context cannot help but be influenced, inspired and sometimes restricted by these policies and political influences. This article examines the contemporary art markets of two emerging, Socialist economies to investigate the relationship between state politics and the contemporary visual arts market. We argue that the respective governments and art worlds are trying to construct a brand narrative for their nations, but that these discourses are often at cross-purposes. In doing so, we illustrate that it is impossible to separate a consideration of the artwork from the macro-level context in which it is produced, distributed, and consumed.
The Story of Hezekiah's Prayer (2 Kings 19) and Jeremiah's Polemic concerning the Inviolability of Jerusalem
Authors: Baruchi-Unna Amitai
Published: March 2015

This article suggests reading the reworked prophetical story of Hezekiah's prayer, which is now the third part of the report of Sennacherib's war against Judah (2 Kgs 19.9b–35), as part of the rather well-documented debate concerning the inviolability of Jerusalem that was propounded during the Babylonian crisis in the last days of the Judean kingdom. Offering slight modifications of two existing theories, this article argues that the royal prayer served as the motive that moved this story forward, and that the list of conquered cities recounted in 2 Kgs 19.12–13 reflects a Neo-Babylonian setting. Based upon this, the story is compared with a parallel account of the deliverance of Jerusalem in the days of Hezekiah recounted during the trial of Jeremiah (Jer. 26.16–19). It is deduced that the two stories reflect similar ideological thought, which suggests that they served the same polemical purpose in the same historical setting.
‘What he did for me’: David's Warning about Joab in 1 Kings 2.5
Authors: Janzen David
Published: March 2015

This article argues that David orders Solomon in 1 Kgs 2.5–6 to kill Joab because of Joab's pattern of assassinating rivals in order to benefit his master. David's point in 2.5 is that Joab killed Abner and Amasa, two potential enemies of David, without warning, and since Joab supported Solomon's brother's claim to the throne, Solomon might be his next victim. The Septuagint and the Lucianic recension have altered the more difficult text that appears in the Masoretic text in order to make it seem as if Joab and harmed David, and so provide a legal and religious basis for David and Solomon's conspiracy to kill Joab not present in the original text.
Modelling and evaluating municipal solid waste management strategies in a mega-city: The case of Ho Chi Minh City
Authors: ThiKimOanh Le , Bloemhof-Ruwaard Jacqueline M , van Buuren Joost CL , van der Vorst Jack GAJ , Rulkens Wim H
Published: March 2015

Ho Chi Minh City is a large city that will become a mega-city in the near future. The city struggles with a rapidly increasing flow of municipal solid waste and a foreseeable scarcity of land to continue landfilling, the main treatment of municipal solid waste up to now. Therefore, additional municipal solid waste treatment technologies are needed. The objective of this article is to support decision-making towards more sustainable and cost-effective municipal solid waste strategies in developing countries, in particular Vietnam. A quantitative decision support model is developed to optimise the distribution of municipal solid waste from population areas to treatment plants, the treatment technologies and their capacities for the near future given available infrastructure and cost factors.
The effect of copolymer composition on the batch foaming dynamics of styrene/methylmethacrylate copolymers
Authors: Azimi Hamid Reza , Rezaei Mostafa , Salehi Mostafa
Published: March 2015

In this work, styrene/methyl methacrylate (St/MMA) copolymer particles were synthesized by suspension polymerization process with different copolymer compositions to study the visual batch foaming dynamics. The visualization system consisted of the self-sealing observation cell equipped to the pressure and temperature controller. The synthesized copolymer particles were impregnated by n-pentane, followed by recording of particle expansion. The cell structure of foams was studied by scanning electron microscopy. The effect of different foaming conditions on the expansion behavior of copolymers was examined. It was concluded that sorption pressure and temperature have contradictory effects on the foaming ratio of the synthesized copolymers at lower and higher sorption pressures, and the results were confirmed with the foams’ cell structure. Furthermore, it was shown that, at different temperatures and pressures, the expansion behavior change dramatically with increasing of MMA content in the copolymer.
Neurotoxicity of mycotoxins produced in vitro by Penicillium roqueforti isolated from maize and grass silage
Authors: Malekinejad H , Aghazadeh-Attari J , Rezabakhsh A , Sattari M , Ghasemsoltani-Momtaz B
Published: March 2015

Fungal growth in human foods and animal feeds causes profound damage indicating a general spoilage, nutritional losses, and the formation of mycotoxins. Thirty apparently contaminated maize and grass silage samples were analyzed for the presence of total fungi. Penicillium roqueforti were isolated from all (100%) moldy silage samples on general and selective culture media. Furthermore, P. roqueforti-positive samples culture media subjected to the toxin extraction and toxins of patulin, penicillic acid, mycophenolic acid, and roquefortin-C (ROQ-C) were identified by means of high-performance liquid chromatography method. Cytotoxicity of identified toxins was investigated on neuro-2a cells. Alamar blue reduction, neutral red uptake, and intracellular adenosine triphosphate (ATP) content assays indicated that patulin and ROQ-C exert the strongest and weakest toxicity, respectively. Reactive oxygen species (ROS) generation by the toxins-exposed cells was measured, and the results supported the mitochondrial and lysosomal dysfunction and ATP depletion in exposed cells. Our data suggest that P. roqueforti is the widely present mold in analyzed maize and grass silage samples, which is able to produce toxins that cause neurotoxicity. This finding may explain in part some neuronal disorders in animals, which are fed contaminated feedstuffs with mentioned fungus. Moreover, mitochondrial and lysosomal dysfunction, intracellular ATP depletion, and the excessive ROS generation were found as the mechanisms of cytotoxicity for P. roqueforti-produced toxins.
Effect of palonosetron (5HT-3 antagonist) and pantoprazole (proton pump inhibitor) against surgical esophagitis induced by forestomach and pylorus ligation in albino rats
Authors: Kumar A , Gautam S , Rawat JK , Singh M , Saraf SA , Kaithwas G
Published: March 2015

This study was embarked upon to evaluate the effects of pantoprazole and palonosetron on experimental esophagitis in albino wistar rats. Groups of rats, fasted for 36 h, were subjected to pylorus and forestomach ligation, supervened by treatment with normal saline (3 ml/kg, po, sham control), esophagitis control (3 ml/kg, po), pantoprazole (30 mg/kg, po), palonosetron (0.5 mg/kg, po), and their combination. Animals were sacrificed after 12 h and appraised for the volume of gastric juices, total acidity, free acidity, and esophagitis index. Esophageal tissues were further figured out biochemically for markers of oxidative stress and inflammatory mediators. The combination therapy comparably inhibited the esophagitis index (52.86%), gastric volume (66.04%), free acidity (43.76%), and total acidity (42.60%) in comparison with toxic control. The combination therapy also subsidized the biochemical and inflammatory markers to the purview less than toxic control. The morphological changes were scrutinized by scanning electron microscopy and were observed to demonstrate momentous protection by the amalgamation therapy. Combination therapy with pantoprazole and palonosetron flaunted sententious protection against experimental esophagitis.
Expressive Devices and Perceived Musical Character in 34 Performances of Variation 7 from Bach's Goldbergvariations
Authors: Fabian Dorottya , Schubert Emery
Published: March 2015

Ninety-eight undergraduate music students rated thirty-four commercial sound recordings of Bach's variation 7 from the Goldberg Variations in an attempt to better understand the relationship between performance features and perceived musical character. The movement is in 6/8 and is characterised by a repeating dotted pattern. The piece is known to be played to express a variety of musical characters because of the two versions of the piece, one implying a pastorale interpretation, the other a gigue. Past literature predicted the performance of dotting to be the most important determining factor in establishing musical character in eighteenth century compositions where dotted patterns prevail. However, recent research suggests that the perception of dotting is convoluted by articulation and tempo. Using clustering techniques, five distinct and varied musical characters were evoked consistently across the performances (each cluster represented by the word bright, playful, delicate, majestic or agitated), as judged by the participants using an adjective checklist. The same participants rated the following performance features: tempo, articulation, dotting and loudness. Each of these features made statistically significant contributions in distinguishing between character clusters. However, dotting made a relatively small contribution. Regression analysis indicated that 65% of variation in judged dotting response could be explained as a linear combination of articulation and tempo. The study suggests that reducing musical character to dotting neglects the more significant contribution made by articulation, tempo and loudness.
Emotion-Related Responses to Audio News with Rising versus Falling Background Tone Sequences
Authors: Kallinen Kari , Ravaja Niklas
Published: March 2015

We examined the emotional effects of (a) a rising versus a falling chromatic tone sequence in the background of audio news and (b) foreground versus background diatonic and chromatic tone sequences. In experiment one, 26 participants rated audio news messages with rising and falling chromatic background tone sequences on the valence and arousal dimensions. Cardiac activity, electrodermal activity (EDA), and facial muscle activity were also recorded continuously. In experiment two, 24 participants rated six plain tone sequences ( i.e., rising and falling chromatic, major, and minor) and six news messages with the aforementioned tone sequences mixed in the background on the valence and arousal dimensions. In experiment 1, both self-reported arousal and physiological arousal as measured by EDA were higher during the news with a rising-tone sequence compared to those with a falling-tone sequence. In experiment 2, rising-tone sequences prompted both higher arousal and pleasantness ratings. However, the responses were moderated by the type of listening task: foreground listening prompted responses related to musical connotations ( i.e., major tone sequences were rated as most pleasant and minor as most unpleasant), whereas background listening prompted responses dependent on the emotional congruence between the news messages and tone sequences ( i.e., the minor mode versions were rated as most pleasant and the major mode versions as most unpleasant). In addition, level of education-, music listening frequency-, and age-related differences in the responses were found and are discussed.
Entrenched gendered pathways in science, technology, engineering and mathematics: Engaging girls through collaborative career development
Authors: Broadley Kate
Published: March 2015

Gendered educational and occupational pathways are entrenched in many countries. The underrepresentation of women in the science, technology, engineering and mathematics (STEM) fields has ramifications for individuals and for workforces. Girls’ declining interest in STEM coincides with an increasing demand for STEM-skilled professionals across the globe. This conceptual analysis establishes the extent of STEM gender inequality in Australia and argues that the lack of women in these fields is problematic. Research using Eccles’ expectancy-value theory explains gender differences in mathematics and science expectations and values. Implications for career advisers are outlined including: recommendations for engaging girls in STEM while they are in primary school; collaborating with teachers; using role models and mentors; working with families to promote STEM; and focussing on specific groups of girls. The aim of this analysis is to assist career advisers to explore STEM educational and occupational pathways with girls.
The potential for utilising the collaborative learning spaces approach in the delivery of résumé development education
Authors: Dobinson Troy , Stokes-Thompson Frederick
Published: March 2015

This study investigated the potential for using collaborative learning spaces for the development of résumé writing knowledge and skills in higher education students. Utilising a collaborative learning environment, 227 students from a mix of programmes and year levels participated in one of 24 workshops centering on a technology supported, shared review and reflection approach to résumé construction. It was concluded that use of technology supported collaborative learning spaces has the potential to be a valuable, innovative approach for the delivery of career management related skills in higher education.
The Effects of Check, Connect, and Expect on Behavioral and Academic Growth
Authors: McDaniel Sara C. , Houchins David E. , Robinson Cecil
Published: March 2015

Check, Connect, and Expect (CCE) is a secondary tier behavioral intervention that provides students with levels of support including a dedicated “coach” for check-in and check-out procedures, and social skills instruction. Elementary students ( n = 22) in an alternative education school setting received CCE for 13 weeks following 4 weeks of baseline data collection. Measures included (a) daily progress reports (DPR), (b) direct observation of academic engagement, and (c) curriculum-based measures of academic growth (math calculation and oral reading fluency). These measures were used to examine the relationship between CCE and student outcomes using an interrupted time series design and multilevel growth curve modeling. This quasi-experimental within-subjects design compared the slopes and intercepts of baseline student data with intervention student data. Results demonstrate that students displayed statistically significant improvement on DPRs at the onset of CCE and demonstrated positive behavioral growth during CCE. There was also a statistically significant improvement of academic engagement at the onset of CCE. There was no statistically significant change in academic performance. A description of potential moderating variables, future research directions, and practical significance is presented.
A parametric investigation on the microelastohydrodynamic lubrication of power law fluid lubricated line contact
Authors: Thakre Gananath D , Sharma Satish C , Harsha SP , Tyagi MR
Published: March 2015

A parametric study of microelastohydrodynamic lubrication contact between rough cylinder and plane lubricated with non-Newtonian power law fluid is carried out. A Gaussian rough surface is considered and modeled using stochastic approach. A theoretical solution of pressure distribution, fluid film thickness, and friction for given speeds, material properties, slide-to-roll ratio, and power law index, is obtained by solution of Reynolds equation using finite element method techniques. An isotropic roughness pattern is considered and results are obtained for wide range of operating parameters. The results indicate that the shear-thickening fluids provide thicker lubricant films as compared to shear-thinning fluids. The minimum fluid film thickness is observed to decrease with an increase of load and it increases with an increase of speed and material parameter. Slide-to-roll ratio has a marginal influence of the minimum film thickness. Under certain operating conditions, softer materials with shear-thickening lubricants yield thicker lubricant films than the harder materials lubricated with shear-thinning fluids. The coefficient of friction too is influenced by the rheology of lubricants with shear-thinning fluids providing larger values of coefficient of friction than the shear-thickening fluids.
‘A world turned upside down’: Emotional labour and the professional dominatrix
Authors: Pinsky Dina , Levey Tania G.
Published: March 2015

The professional dominatrix, who has been underrepresented in the literature on sex work, complicates our understanding of the emotional labour of sex work. The professional dominatrix is paid by clients to perform the role of the dominant in scenarios involving bondage, discipline, dominance, submission, sadomasochism, and ‘fetishism.’ Unlike other sex workers, who must often feign interest and act flirtatiously in order to make clients feel desired, the dominatrix is asked, at times, to express emotional displays such as indifference or displeasure. At the same time, our analysis of in-depth interviews, published memoirs, and blogs reveals multifaceted and dynamic constructions of emotional labour that would typically be considered contradictory and unpredictable from the point of view of normative emotional displays in work. While her job is defined by dominance and can at times involve aggression, compassionate and care-taking traits are perhaps just as important in defining her emotional labour. In contrast to research that poses dichotomous models of gender and emotional labour, we present a more fluid paradigm that resists simplistic connections between gender, emotions, and work.
Talking about the city: Focus group discussions about the city and the community as developmental grounds with children aged 5–17
Authors: Lúcio Joana
Published: March 2015

Due to its complexity, size, diversity (internal or external) and meanings, it is possible to analyse the city from various points of view, which are, ultimately, references for the construction of knowledge about the urban space, and the logic of apprehension and appropriation used by individuals and organizations in relation to the place they inhabit. The city is, increasingly, a context for isolation and exclusion, where individuals share fewer experiences, which therefore become less significant. The effective range of action each person or group has towards the city is clearly limited. This interferes with the process of producing practical and emotional meanings, since the message conveyed is that such a space is defined ‘in spite of people’ and not ‘because of people’. In this article, the author mobilizes the productions of children between the ages of 5 and 17 in an attempt to capture their perceptions (their discourse) about urban life and education, as well as their appropriations (their projects), either past, present or future. In the process, the author also discusses focus groups as platforms for participation in the community context.
Encountering methodology through art: A Deleuzoguattarian territory of action research
Authors: Smith Ruth
Published: March 2015

The philosophy of Deleuze, and his collaborative work with Guattari, has begun to appear in the field of action research. This article seeks to build on this scholarship through a discussion of the literature in which Deleuzoguattarian concepts are used to reconsider action research methodology. Framing action research as territory, I suggest that artmaking can facilitate the creation of new ideas, thus initiating the process of deterritorialization. For an examination of the concepts used and the implications for action research methodology, I draw from my experience creating art as an action researcher with a local Somali nonprofit organization.
The Role of Social Interaction Element on Intention to Play MMORPG in the Future
Authors: Tan Wee Kheng , Yeh Yi Der , Chen Ssu Han
Published: March 2015

Few studies examine how massively multiplayer online role-playing game (MMORPG) players react when they are faced with constraints that prevent them from continuing to play the game or to play as much as they desire. This study used the concept of leisure constraint negotiation process and social capital construct to understand how players deal with the above situation by initiating negotiation strategies to mitigate the constraints. Using partial least squares method as the analytical tool, this empirical study showed that the social interaction element of MMORPG plays a major role in influencing the outcomes of the negotiation process. Social capital plays a role in propelling negotiation strategies, and different types of social capitals are needed to trigger different negotiation strategies. This study further demonstrates: which negotiation strategy is triggered depends on which constraints and negotiation strategies matter most to the leisure seekers. There is also a need for congruence between motivation and negotiation strategy.
How Do Fibromyalgia Patients With Alexithymia Experience Their Body? A Qualitative Approach
Authors: Calsius Joeri , Courtois Imke , Stiers Jolien , De Bie Jozef
Published: March 2015

Patients suffering from chronic pain such as fibromyalgia (FM) not only experience change in their physical bodies but also in their embodiment. There are two forms of disturbed body awareness (BA), namely, “disembodiment” and “hyper-embodiment.” This study describes how patients with FM experience their body and whether there is a difference in BA with or without alexithymia. Based on two self-report questionnaires (Toronto Alexithymia Scale [TAS]-20 and Hospital Anxiety and Depression Scale [HADS]), a purposeful sample of FM patients with and without alexithymia was included. Two focus groups were conducted with nine alexithymic and six nonalexithymic FM patients and were analyzed by a Interpretative Phenomenological Analysis. Body experience appeared in two themes: “the lived body as hyper present” and “alienation from the lived body.” A third theme emerged as “the lived body in interaction with others” and indicates the importance of the interpersonal aspect of BA. We found no differences regarding BA between the alexithymic and nonalexithymic patients. These results suggest that BA in FM patients cannot exclusively be classified under the constructs of hyper- or disembodiment. The authors suggest to consider embodiment in FM, subjected to intra- as well as interindividual influences, as a dimensional construct whereby the equilibrium tends to hyper-embodiment. Still, a temporary shift of this equilibrium from hyper- to disembodiment due to certain emotional state or stress is possible. As alexithymia had no influence on the description of BA, it seems that FM patients primarily fail to express their BA without in fact being disembodied.
The role of hematologists in a changing United States health care system
Authors: Wallace Paul J. , Connell Nathan T. , Abkowitz Janis L.
Published: March 2015

Major and ongoing changes in health care financing and delivery in the United States have altered opportunities and incentives for new physicians to specialize in nonmalignant hematology. At the same time, effective clinical tools and strategies continue to rapidly emerge. Consequently, there is an imperative to foster workforce innovation to ensure sustainable professional roles for hematologists, reliable patient access to optimal hematology expertise, and optimal patient outcomes. The American Society of Hematology is building a collection of case studies to guide the creation of institutionally supported systems-based clinical hematologist positions that predominantly focus on nonmalignant hematology. These roles offer a mix of guidance regarding patient management and the appropriate use and stewardship of clinical resources, as well as development of new testing procedures and protocols.
The role of tyrosine kinases in the pathogenesis of idiopathic pulmonary fibrosis
Authors: Grimminger Friedrich , Günther Andreas , Vancheri Carlo
Published: March 2015

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a median survival time from diagnosis of 2–3 years. Although the pathogenic pathways have not been fully elucidated, IPF is believed to be caused by persistent epithelial injury in genetically susceptible individuals. Tyrosine kinases are involved in a range of signalling pathways that are essential for cellular homeostasis. However, there is substantial evidence fromin vitrostudies and animal models that receptor tyrosine kinases, such as the platelet-derived growth factor receptor, vascular endothelial growth factor receptor and fibroblast growth factor receptor, and non-receptor tyrosine kinases, such as theSrcfamily, play critical roles in the pathogenesis of pulmonary fibrosis. For example, the expression and release of tyrosine kinases are altered in patients with IPF, while specific tyrosine kinases stimulate the proliferation of lung fibroblastsin vitro. Agents that inhibit tyrosine kinases have shown anti-fibrotic and anti-inflammatory effects in animal models of pulmonary fibrosis. Recently, the tyrosine kinase inhibitor nintedanib has shown positive results in two phase III trials in patients with IPF. Here, we summarise the evidence for involvement of specific tyrosine kinases in the pathogenesis of IPF and the development of tyrosine kinase inhibitors as treatments for IPF.
Circulating miRNAs as potential biomarkers of therapy effectiveness in rheumatoid arthritis patients treated with anti-TNFα
Authors: Castro-Villegas Carmen , Pérez-Sánchez Carlos , Escudero Alejandro , Filipescu Ileana , Verdu Miriam , Ruiz-Limón Patricia , Aguirre Ma Angeles , Jiménez-Gomez Yolanda , Font Pilar , Rodriguez-Ariza Antonio , Peinado Juan Ramon , Collantes-Estévez Eduardo , González-Conejero Rocío , Martinez Constantino , Barbarroja Nuria , López-Pedrera Chary
Published: March 2015

Introduction

The advent of anti-tumor necrosis factor alpha (anti-TNFα) drugs has considerably improved medical management in rheumatoid arthritis (RA) patients, although it has been reported to be ineffective in a fraction of them. MicroRNAs (miRNAs) are small, non-coding RNAs that act as fine-tuning regulators of gene expression. Targeting miRNAs by gain or loss of function approaches have brought therapeutic effects in various disease models. The aim of this study was to investigate serum miRNA levels as predictive biomarkers of response to anti-TNFα therapy in RA patients.

Methods

In total, 95 RA patients undergoing anti-TNFα/disease-modifying antirheumatic drugs (anti-TNFα/DMARDs) combined treatments were enrolled. Serum samples were obtained at 0 and 6 months and therapeutic efficacy was assessed. miRNAs were isolated from the serum of 10 patients before and after anti-TNFα/DMARDs combination therapy, cDNA transcribed and pooled, and human serum miRNA polymerase chain reaction (PCR) arrays were performed. Subsequently, selected miRNAs were analyzed in a validation cohort consisting of 85 RA patients. Correlation studies with clinical and serological variables were also performed.

Results

Ninety percent of RA patients responded to anti-TNFα/DMARDs combination therapy according to European League Against Rheumatism (EULAR) criteria. Array analysis showed that 91% of miRNAS were overexpressed and 9% downregulated after therapy. Functional classification revealed a preponderance of target mRNAs involved in reduction of cells maturation - especially on chondrocytes - as well as in immune and inflammatory response, cardiovascular disease, connective tissue and musculoskeletal system. Six out of ten miRNAs selected for validation were found significantly upregulated by anti-TNFα/DMARDs combination therapy (miR-16-5p, miR-23-3p, miR125b-5p, miR-126-3p, miRN-146a-5p, miR-223-3p). Only responder patients showed an increase in those miRNAs after therapy, and paralleled the reduction of TNFα, interleukin (IL)-6, IL-17, rheumatoid factor (RF), and C-reactive protein (CRP). Correlation studies demonstrated associations between validated miRNAs and clinical and inflammatory parameters. Further, we identified a specific plasma miRNA signature (miR-23 and miR-223) that may serve both as predictor and biomarker of response to anti-TNFα/DMARDs combination therapy.

Conclusions

miRNA levels in the serum of RA patients before and after anti-TNFα/DMARDs combination therapy are potential novel biomarkers for predicting and monitoring therapy outcome.
Significant effects of biologic therapy on lipid profiles and insulin resistance in patients with rheumatoid arthritis
Authors: Chen Der-Yuan , Chen Yi-Ming , Hsieh Tsu-Yi , Hsieh Chia-Wei , Lin Chi-Chen , Lan Joung-Liang
Published: March 2015

Introduction

The goal of this study was to investigate (1) the associations of rheumatoid arthritis (RA)-related inflammation or rheumatoid factor/anti-cyclic citrullinated peptide (anti-CCP) positivity with lipid profiles and insulin resistance (IR), (2) the effects of biologic therapy on lipid profiles and IR, and (3) potential predictors for the presence of subclinical atherosclerosis.

Methods

Serum levels of lipid profiles were determined by enzymatic methods in 32 adalimumab-treated patients, 16 etanercept-treated patients, 24 tocilizumab-treated patients, and 20 biologic-naïve patients. Atherogenic index, which corresponds to the ratio of total cholesterol to high-density lipoprotein cholesterol (HDL-C), was calculated. IR was measured by homeostasis model assessment. Pro-inflammatory cytokine levels were examined by enzyme-linked immunosorbent assay. Common carotid artery intima-media thickness was determined by using sonography.

Results

There was an inverse correlation between disease activity (disease activity score for 28 joints, or DAS28) and low-density lipoprotein cholesterol (LDL-C) levels (r = −0.226, P <0.05) and a positive correlation between DAS28 and IR (r = 0.361, P <0.005). Anti-CCP-positive patients had significantly higher DAS28 and IR compared with anti-CCP-negative patients. There was also a positive correlation between IR and levels of interleukin-6 or tumor necrosis factor-alpha (TNF-α). HDL-C levels significantly increased in patients receiving 6-month anti-TNF-α therapy, and levels of total cholesterol, LDL-C, and triglyceride increased in tocilizumab-treated patients. IR significantly decreased in patients under biologic therapy but was unchanged in biologic-naïve patients. Age, IR, and DAS28 were significant predictors of severe subclinical atherosclerosis (odds ratios of 1.08, 2.77, and 2.52, respectively).

Conclusions

Significant associations of RA-related inflammation with lipid profiles and IR indicate the involvement of RA in atherosclerosis pathogenesis. Biologic therapies were associated with IR reduction without change in atherogenic index, but their beneficial effects on atherosclerosis reduction need to be verified in the future.
Clinical characteristics and treatment-related biomarkers associated with response to high-dose interleukin-2 in metastatic melanoma and renal cell carcinoma: retrospective analysis of an academic community hospital’s experience
Authors: Saraceni Christine , Agostino Nicole , Weiss Michael J , Harris Katherine , Nair Suresh
Published: March 2015

Background

Immunotherapy in the treatment of metastatic melanoma and renal cell carcinoma can produce durable therapeutic responses, which may improve survival. We aimed to identify clinical characteristics and biomarkers associated with response to high-dose interleukin-2 therapy (IL-2) in patients with metastatic melanoma and renal cell carcinoma treated at an academic community hospital.

Patients/Methods

We retrospectively analyzed clinical variables and biomarkers of 50 consecutive metastatic melanoma or renal cell carcinoma patients treated at our institution with IL-2 during 2004 – 2012. We evaluated clinical characteristics: metastatic sites of disease, prior therapies, number of IL-2 doses per cycle, response duration, autoimmune phenomena, and peak fever, as well as laboratory biomarkers: baseline LDH, platelet nadir, and baseline and highest absolute lymphocyte count (ALC). Survival outcomes were calculated using Kaplan-Meier curves.

Results

Variables differing between responders (clinical benefit group) and non-responders (no clinical benefit group) in metastatic melanoma included platelet nadir during treatment (p = 0.015), autoimmune phenomena (p = 0.049), and in renal cell carcinoma, platelet nadir (p = 0.026). There were no significant differences between number of doses of IL-2 received per cycle and response in either cancer subtype. Clinical benefit occurred in 25% of patients (9/36) when IL-2 was given as first-line therapy. Median overall survival for the clinical benefit group from the initiation of IL-2 to death or last follow-up was 61 months versus 17 months for the no clinical benefit group (p < 0.001) for metastatic melanoma. In renal cell carcinoma overall survival for clinical benefit patients was 48 months versus 17 months. No treatment-related deaths occurred.

Conclusions

High-dose IL-2 can be safely administered by an experienced team in a non–intensive care oncology unit. The clinical benefit group developed autoimmune phenomena (melanoma patients), lower platelet nadir, and on average, received the same number of IL-2 doses as the no clinical benefit group, suggesting a response relationship to the patient’s baseline immune status. Further investigation of immune predictors of response may be useful to select appropriate patients for this therapy.
Mode I critical fracture energy of adhesively bonded joints between glass fiber reinforced thermoplastics
Authors: Mahaphasukwat Siripong , Shimamoto Kazumasa , Hayashida Shota , Sekiguchi Yu , Sato Chiaki
Published: March 2015

Critical fracture energies of adhesively bonded joints under mode I constant separation were experimentally investigated. Double cantilever beam (DCB) specimens comprising polyamide 6 (PA6) based fiber reinforced thermoplastics (GFRTP) were utilized for the experiments. The adherends of the joints were bonded with three different types of adhesives such as polyurethane and acrylates. A surface treatment method with a primer was applied to pre-bonded surface, matching with the different adhesives, which results in five combinations.

Strongest combination, Plexus Primer PC120 and Plexus AO420, exhibited 2.95 kJ/m2 in mode I critical fracture energy, which is much higher than those of ordinary epoxy adhesive and similar to those of rubber-modified very-ductile epoxy adhesives. Therefore, it is confirmed that adhesive bonding can be applied to join PA6 based GFRTP even for structural use, although the material is thought too difficult to bond adhesively.
Krüppel-like factor 4 is a transcriptional regulator of M1/M2 macrophage polarization in alcoholic liver disease
Authors: Saha Banishree , Bala Shashi , Hosseini Nooshin , Kodys Karen , Szabo Gyongyi
Published: March 2015

Macrophages play an important role in inflammation and liver injury. In ALD, activated macrophages, including M1 (proinflammatory) and M2 (anti-inflammatory) macrophages, are present in the liver. As KLF4 has been described as a regulator of macrophage polarization, we investigated its role in ALD. Chronic alcohol feeding in C57Bl/6 mice led to increased expression of M1 (TNF-α, MCP1, and IL-1β) and M2 (Arg1, Mrc1, and IL-10) genes and the frequency of CD206+CD163+ M2 macrophages in the liver. KLF4 mRNA and protein levels were increased in the livers of EtFed compared with PF mice. In macrophages, in vivo and in vitro, EtOH increased KLF4 levels, transcriptional activity, and expression of M1 and M2 genes. KLF4 knockdown and overexpression experiments demonstrated alcohol-dependent and -independent functions of KLF4 in regulating M1 and M2 markers. KLF4 siRNA treatment, alone and in synergy with alcohol, increased the levels of M1 markers. In contrast, KLF4 overexpression increased the levels of M2 and decreased M1 markers, and this was enhanced further by alcohol. KLF4 was regulated by alcohol and its metabolites. KLF4 mRNA and activity were increased in the presence of 4-MP, an inhibitor of ADH, and CYP2E1. However, inhibition of acetaldehyde breakdown attenuated KLF4 induction and promoted M1 polarization. We conclude that KLF4 regulates M1 and M2 markers in ALD. EtOH promotes KLF4 and M2 phenotype, whereas acetaldehyde attenuates KLF4 and promotes M1 macrophage, which may explain the increased presence of M1 and M2 macrophage populations in ALD.
Allelic variation in 5-HTTLPR and the effects of citalopram on the emotional neural network
Authors: Ma Yina , Li Bingfeng , Wang Chenbo , Zhang Wenxia , Rao Yi , Han Shihui
Published: March 2015

Background

Selective serotonin reuptake inhibitors (SSRIs), such as citalopram, which selectively block serotonin transporter (5-HTT) activity, are widely used in the treatment of depression and anxiety disorders. Numerous neuroimaging studies have examined the effects of SSRIs on emotional processes. However, there are considerable inter-individual differences in SSRI effect, and a recent meta-analysis further revealed discrepant effects of acute SSRI administration on neural responses to negative emotions in healthy adults.

Aims

We examined how a variant of the serotonin-transporter polymorphism (5-HTTLPR), which affects the expression and function of 5-HTT, influenced the acute effects of an SSRI (citalopram) on emotion-related brain activity in healthy adults.

Method

Combining genetic neuroimaging, pharmacological technique and a psychological paradigm of emotion recognition, we scanned the short/short (s/s) and long/long (l/l) variants of 5-HTTLPR during perception of fearful, happy and neutral facial expressions after the acute administration of an SSRI (i.e. 30mg citalopram administered orally) or placebo administration.

Results

We found that 5-HTTLPR modulated the acute effects of citalopram on neural responses to negative emotions. Specifically, relative to placebo, citalopram increased amygdala and insula activity in l/l but not s/s homozygotes during perception of fearful faces. Similar analyses of brain activity in response to happy faces did not show any significant effects.

Conclusions

Our combined pharmacogenetic and functional imaging results provide a neurogenetic mechanism for discrepant acute effects of SSRIs.
Seismic and Progressive Collapse Assessment of New Proposed Steel Connection
Authors: Faridmehr Iman , Osman Mohd Hanim , Tahir Mahmood Md , Nejad Ali Farokhi , Azimi Mohammadamin
Published: March 2015

The performance of a new proposed steel connection against seismic loading and progressive collapse was experimentally and numerically investigated in this paper. The seismic performance included interstory drift angle and flexural strength evaluated in accordance with 2010 AISC Seismic Provisions whereas progressive collapse assessment was based on satisfaction of the acceptance criteria by rotational capacities of the connection provided in UFC 4-023-03 guideline. The results confirmed that the new proposed connection was capable of achieving adequate rotational capacity and developing the full inelastic capacity of the connecting beam. In addition, an excellent cyclic behavior was demonstrated by proposed connection which enhance interstory drift angle. Based on the results the proposed connection has adequate intensity and ductility to classify it as full-strength and ductile connection.
The Effect of an above Real Time Decision-Making Intervention on Visual Search Behaviour
Authors: Lorains Megan , Panchuk Derek , Ball Kevin , MacMahon Clare
Published: March 2015

The investigation of visual search strategies allows researchers to further understand expertise in sport. This research measured the visual search strategies of six elite Australian Football athletes during the course of a five-week speeded video decision-making training intervention. There were two athletes in each intervention group; normal speed and above real time video, and two athletes in the control group. Athletes were asked to watch a series of video clips of match-day footage and click on the screen where they would place the ball if in possession. Eye movements were collected at the pre-test, third training session, post-test and retention test. Results revealed that following training, regardless of video speed, the fixation duration became longer compared to those who had no video training. This significant finding falls in line with previous research. Furthermore, the above real time training group spent a longer duration fixating on the best option after the retention test, compared to other groups. These results provide a solid base for future research in sport to track changes in eye movements throughout training and learning.