bluuebunny/crossref_metadata_2025 huggingface dataset:
Network Sampling with Memory
Authors: Mouw Ted , Verdery Ashton M.
Published: November 2012

Techniques for sampling from networks have grown into an important area of research across several fields. For sociologists, the possibility of sampling from a network is appealing for two reasons: (1) A network sample can yield substantively interesting data about network structures and social interactions, and (2) it is useful in situations in which study populations are difficult or impossible to survey with traditional sampling approaches because of the lack of a sampling frame. Despite its appeal, methodological concerns about the precision and accuracy of network-based sampling methods remain. In particular, recent research has shown that sampling from a network using a random walk–based approach such as respondent-driven sampling (RDS) can result in a high design effect (DE): the ratio of the sampling variance to the sampling variance of simple random sampling (SRS). A high DE means that more cases must be collected to achieve the same level of precision as SRS. In this article, we propose an alternative strategy, network sampling with memory (NSM), which collects network data from respondents to reduce DEs and, correspondingly, the number of interviews needed to achieve a given level of statistical power. NSM combines a “list” mode, in which all individuals on the revealed network list are sampled with the same cumulative probability, with a “search” mode, which gives priority to bridge nodes connecting the current sample to unexplored parts of the network. We test the relative efficiency of NSM compared with RDS and SRS on 162 school and university networks from the National Longitudinal Study of Adolescent Health and Facebook that range in size from 110 to 16,278 nodes. The results show that the average DE for NSM on these 162 networks is 1.16, which is very close to the efficiency of a simple random sample (DE = 1) and 98.5 percent lower than the average DE we observed for RDS.
Barra da Tijuca
Authors: Herzog Lawrence A.
Published: November 2012

In Rio de Janeiro, Brazil’s second-largest metropolis, an important new form of early-twenty-first-century peripheral development that deserves critical inquiry has emerged—the “global suburb.” In Brazil, these suburbs take the form of gated high-rise compounds providing upper- and middle- upper-income residents enclaves of security amidst what they perceive as the chaos and uncertainty of cities overrun by favelas, crime, and gang-related conflict. The Barra da Tijuca suburban enclave in Rio de Janeiro offers a poignant case study of a development project that was initially conceived as an innovative urban design plan for a modernist “new town” but, with little opposition from government officials and planners, was subsequently absorbed by private developers and turned into an elite, U.S.-style suburb.

En Rio de Janeiro, metrópolis segunda mas grande de Brasil, emerge al comienzo del siglo veintiuno una forma de desarrollo periférico importante y nueva que se merece una pregunta critica—el “suburbio global.” En Brasil estos suburbios toman la forma de recitos amurallados de edificios de gran altura los cuales proveen a las clases de gran y alto-medio ingreso enclavas de seguridad en medio de lo que perciben es el caos y incertidumbre de ciudades sobrantes de favelas, el crimen, y el conflicto relacionado con el pandillismo. La enclava suburbana de la Barra de Tijuca en Rio de Janeiro ofrece un caso conmovedor de un proyecto urbano originalmente concebido como un diseño urbano innovador para un “pueblo nuevo” modernizado pero, con poca oposición de parte de los oficiales gubernamentales y planificadores, fue absorbido por el fomento privado y convertido en un suburbio tipo Estados Unidos para una elite.
Thermal decomposition of fire-retarded high-impact polystyrene and high-impact polystyrene/ethylene–vinyl acetate blend nanocomposites followed by thermal analysis
Authors: Katančić Zvonimir , Travaš-Sejdić Jadranka , Hrnjak-Murgić Zlata , Jelenčić Jasenka
Published: November 2012

Blend nanocomposites of high-impact polystyrene and ethylene–vinyl acetate at a ratio of 3:1, with the addition of aluminum hydroxide Al(OH)3 and diphenyl 2-ethylhexyl phosphate (DPO) as fire retardants (FRs) and silica (SiO2) nanofiller were prepared by extrusion. Thermal decomposition, mechanism and kinetics of degradation of the studied samples were characterized by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The fire-retarded samples were characterized by following the degradation kinetics obtained from TGA data by recording the samples at four different heating rates. That enables us to determine one of the kinetic parameters, activation energy ( Ea) of thermal decomposition. The effect of high concentration of FRs on morphology and properties of the studied samples were analyzed by scanning electron microscopy and mechanical properties. The obtained results show that the FRs delay thermal decomposition, particularly in combination with SiO2 nanofiller, which significantly contributes to slowing down the degradation process.
A cross-national study on mobile business: how will ecosystems evolve?
Authors: Park Jinsoo , Choi Minjung
Published: November 2012

This paper tries to identify what shapes the mobile services industry and what changes will take place to the worldwide mobile business. Two case markets are introduced for comparison and analysis: Japan and Finland. Japan is an exemplar country where both the mobile subscription penetration rate and the revenue from data transfer are world record high. Finland is a birthplace of the world’s leading handset manufacturer as well as the center for a substantial number of innovations in Europe. The two countries represent a stark contrast in the industry structure: vertical and integrated vs. horizontal and modular. After an in-depth comparison of the two markets, a brief prospect of the future mobile industry is provided.
An educational package that supports laycarers to safely manage breakthrough subcutaneous injections for home-based palliative care patients: Development and evaluation of a service quality improvement
Authors: Healy Sue , Israel Fiona , Charles Margaret A , Reymond Liz
Published: November 2012

Background:

Palliative care services strive to support people to live and die well in their chosen environment, with optimal symptom control and a pattern of care supportive of laycarers. The likelihood of patients remaining at home often depends upon laycarers, who may be required to manage subcutaneous medications.

Aim and Design:

This study reports the development, trial and evaluation of a package that teaches laycarers to manage subcutaneous medications used for symptom control in home-based patients. The package was developed by palliative care stakeholders and comprises an educational session, delivered by nurses, and a range of demonstrative, audiovisual and written resources.

Settings/Participants:

The package was trialled across 24 sites and was evaluated by 76 laycarers (pre- and post-use) and 53 nurses (at study completion).

Results:

Outcomes of primary interest were perceived global usefulness of the package and rated relevance of components. Laycarers and nurses rated the usefulness and relevance of the package highly – all means were above 5 on a 7-point scale. Also, laycarers were invited to comment on the package, and three focus groups for 26 nurses explored post hoc issues following package implementation.

Conclusions:

In terms of the palliative patient’s illness trajectory, consensus was that the time for package introduction depended upon each particular clinical situation and laycarer. Nursing opinion was divided concerning whether it is safe and appropriate for laycarers to manage subcutaneous injections. Nevertheless, this study demonstrates that the package supports laycarers to manage subcutaneous medications. This has important implications for families, services and health-care systems.
The Impact of Revenue Diversification on Expected Revenue and Volatility for Nonprofit Organizations
Authors: Mayer Walter J. , Wang Hui-chen , Egginton Jared F. , Flint Hannah S.
Published: November 2012

We investigate the relationship between revenue diversification and volatility for nonprofits. Modern portfolio theory suggests that more diversification reduces volatility at the expense of reduced expected revenue. We find that this relationship should not be taken for granted. We use a new empirical measure of volatility that addresses estimation issues of expected revenue, including heteroskedasticity and the omission of the effect of diversification on expected revenue. We also examine the impact on nonprofits of different types of diversification. We find that the effects of diversification on volatility and expected revenue depend on the compositional change in the portfolio. For example, a more diversified portfolio achieved by replacing earned income with donations reduces both volatility and expected revenue, while replacing investment income with donations to achieve an increase in diversification of the same magnitude reduces volatility and increases expected revenue. This suggests other motives for nonprofit organizations to hold investments.
Combination of flotation and flame atomic absorption spectrometry for determination, preconcentration and separation of trace amounts of metal ions in biological samples
Authors: Ghaedi Mehrorang , Niknam Khodabakhsh , kokhdan Syamak Nasiri , Soylak Mustafa
Published: November 2012

An efficient enrichment procedure based on the combination of flame atomic absorption spectrometry (FAAS) and flotation for determination of Cd2+, Ag+ and Zn2+ ions in various biological samples using new collector is studied. The influence of pH, amount of 2-(((1H-benzo[d]imidazol-2-yl)methoxy)methyl)-1H-benzo[d]imidazole (HBIMMHBI) as collector, sample matrix, type and amount of eluting agent, type and amount of surfactant as floating agent, ionic strength and air flow rates on the extraction efficiency were evaluated and optimized. It is ascertained that under study metal ions is preconcentrated simultaneously from matrix in the presence of 0.005 M HBIMMHBI, 0.085% (w/v) of SDS form 750 mL at pH 6.5. The floated complexes metal ions eluted quantitatively with 6 mL of 1.0 M HNO3 in methanol lead to achieve preconcentration factor of 125. The detection limits for analyte ions were in the range of 1.3–2.4 ng mL-1, with recoveries more than 95% and relative SD lower than 4%.
“Othering” agricultural biotechnology: Slovenian media representation of agricultural biotechnology
Authors: Zajc Jožica , Erjavec Karmen
Published: November 2012

While studies on media representations of agricultural biotechnology mostly analyse media texts, this work is intended to fill a research gap with an analysis of journalistic interpretations of media representations. The purpose of this project was to determine how news media represent agricultural biotechnology and how journalists interpret their own representations. A content and critical discourse analysis of news texts published in the Slovenian media over two years and in-depth interviews with their authors were conducted. News texts results suggest that most of the news posts were “othering” biotechnology and biotechnologists: biotechnology as a science and individual scientists are represented as “they,” who are socially irresponsible, ignorant, arrogant, and “our” enemies who produce unnatural processes and work for biotechnology companies, whose greed is destroying people, animals, and the environment. Most journalists consider these representations to be objective because they have published the biotechnologists’ opinions, despite their own negative attitudes towards biotechnology.
Fatty acid composition in hybrid pigs as based on local fatty Lithuanian breed and wild boar
Authors: Razmait ė V , Švirmickas GJ
Published: November 2012

The study was designed to investigate the fatty acid composition in longissimus dorsi (LD) and semimembranosus muscles (SM) and subcutaneous tissue of hybrid (1/4 Lithuanian indigenous wattle, 1/4 wild boar and 1/2 Yorkshire or 1/2 Landrace) pigs. The SM showed a tendency to have lower contents of monounsaturated fatty acids (MUFA) and higher contents of polyunsaturated fatty acids (PUFA) than the LD muscle. No statistically significant differences were observed between the muscles in lipid quality indices, i.e., atherogenic (AI) and thrombogenix (TI) indices and the ratio of hypocholesterolemic and hypercholesterolemic fatty acids (h/H). In the SM, the content of PUFA from Yorkshire-sired hybrids was relatively 47.8% higher, including C18:2n-6, C20:4n-6 and DPA (C22:5n-3) that were higher, respectively, by 44.3%, 86.6% and 51.6% in comparison with those from Landrace-sired hybrids. The gilts had a lower content of MUFA, including C18:1 and C20:1n-9 fatty acids in the LD muscle and tended to have a higher content of PUFA in the SM compared to the barrows. Neither the terminal breed in crossing, nor the gender had any significant effects on the proportions of total saturated, MUFA and PUFA in the subcutaneous tissue.
Changes in Quality and Biochemical Parameters in ‘Idared’ apples during Prolonged Shelf Life and 1-MCP treatment
Authors: Bizjak Jan , Slatnar Ana , Stampar Franci , Veberic Robert
Published: November 2012

In this study, changes in quality and various biochemical parameters of ‘Idared’ apples during prolonged shelf life period after ultra-low oxygen (ULO) storage were investigated. Additionally, the impact of the postharvest application of 1-methylcyclopropene (1-MCP) on different parameters was evaluated. After the harvest, apples were stored in the ULO storage for 6 months and then exposed to room temperature. Fruit firmness, peel color, and changes in sugars, organic acids and phenolics were monitored during the 3 weeks of shelf life. Malic acid, sugars and firmness decreased at room temperature. However, the color of the apples remained unchanged. The level of citric and ascorbic acid remained constant. Levels of phenolics in the peel increased significantly, whereas remained constant in the pulp of apples. 1-MCP treatment resulted in higher amounts of fructose and glucose, malic acid and greater firmness of apples. However, 1-MCP did not influence the phenolic content, ascorbic acid or color. The results obtained indicate that the content of different health-promoting compounds of apples does not change dramatically at room temperature. At the same time these results suggest that 1-MCP could be useful for maintaining certain quality and biochemical parameters and might extend the shelf life of apples.
Psychiatric Home Health Care Skilled Nursing Services
Authors: Thobaben Marshelle
Published: November 2012

Skilled psychiatric nursing services can be an integral component of Medicare certified home health care agencies. Medicare will reimburse home health care agencies for psychiatric nursing home visits on an intermittent basis for qualified psychiatric clients who are under the care of a psychiatrist, have psychiatric diagnoses, and are homebound secondary to psychological or medical problems. Clients’ diagnosed psychiatric disorders may include dementia, schizophrenia, depression, anxiety, bipolar disorder, and substance abuse. Nursing services are provided under a plan of care that is developed and signed by a psychiatrist in consultation with psychiatric nurse and reviewed at least every 60 days by the psychiatrist.
The Multiple Systems Model of Angry Rumination
Authors: Denson Thomas F.
Published: November 2012

Angry rumination is perseverative thinking about a personally meaningful anger-inducing event and is a risk factor for aggression. This article presents a new model for understanding angry rumination across five levels of analysis: cognitive, neurobiological, affective, executive control, and behavioral. The type of rumination that occurs at the cognitive level moderates affective responding and neurobiological activation, which influences executive control and aggression. Angry rumination recruits brain regions implicated in cognitive control, emotion regulation, negative affect, physiological arousal, social cognition, and self-reflection on emotional states. Moreover, angry rumination temporarily reduces self-control, which can increase aggression. The article suggests a functional account of angry rumination, identifies gaps in our knowledge, and proposes future research directions based on hypotheses derived from the model.
A Critical Examination of Popular Assumptions About the Benefits and Outcomes of Monogamous Relationships
Authors: Conley Terri D. , Ziegler Ali , Moors Amy C. , Matsick Jes L. , Valentine Brandon
Published: November 2012

In this article, we critically examine the social institution of monogamy. First, we discuss the lack of an adequate and consistent definition of the construct of monogamy and consider how common monogamy is. Next, we address perceived benefits of monogamy and whether those ostensible benefits are supported by empirical evidence. We conclude that evidence for the benefits of monogamy relative to other relationship styles is currently lacking, suggesting that, for those who choose it, consensual non-monogamy may be a viable alternative to monogamy. Implications for theories of close relationships are discussed.
Evaluation in management education: A visual approach to drawing out emotion in student learning
Authors: Ward Jenna , Shortt Harriet
Published: November 2012

This article introduces a confluent method of evaluation from the qualitative paradigm that encourages student feedback via a sensory route, namely, participant-produced drawings. Through a phenomenological qualitative inquiry carried out at a UK university where the use of participant-produced drawings were piloted, three areas for consideration with regards to enhancing the evaluation of undergraduate provision in management education were identified: (a) giving students space to emotionally respond to their learning, (b) acknowledging the temporal aspect of student learning and (c) offering students the opportunity to set and shape the evaluative agenda. Participant-produced drawing is offered as a method of evaluation that is appreciative of the cognitive-affective learning debate and the rapidly changing nature of higher education practice. We argue that this method provides rich evaluative data on the affective nature of learning that is not as easily explored by traditional, quantitative methods.
The ironies of leadership: insights from a narrative analysis of the TV Western drama series, Rawhide
Authors: Watson Cate
Published: November 2012

Constructs of leadership remain deeply contested despite the research effort expended in this area, suggesting that alternative approaches yielding different insights may prove useful to furthering understanding of this enigmatic concept. In this article I adopt a narrative approach to explore constructions of leadership in and through the TV Western drama series Rawhide, a cattle drive epic, in which leadership is a central theme. Here, I present two readings of leadership as portrayed by trail boss Gil Favor and I draw on this double movement and the possibilities for ironic epiphany opened up by it in analysing leadership. The first reading addresses the text through the lens(es) of leadership theory drawing on both contemporary theory ( Rawhide was first broadcast between 1959–1965) and more recent constructs. This analysis of the text produces insights into the epistemic constraints, or social discourses, which surround its production; the second reading looks for ways to disrupt the narrative of leadership presented. This gives rise to paradox and produces leadership as irony. The article concludes by considering the implications of this for conceptualizing leadership.
Multiple sclerosis risk genotypes correlate with an elevated cerebrospinal fluid level of the suggested prognostic marker CXCL13
Authors: Lindén M , Khademi M , Lima Bomfim I , Piehl F , Jagodic M , Kockum I , Olsson T
Published: November 2012

Background:

The mechanisms of multiple sclerosis (MS) pathogenesis are still largely unknown. The heterogeneity of disease manifestations make the prediction of prognosis and choice of appropriate treatment protocols challenging. Recently, increased cerebrospinal fluid (CSF) levels of the B-cell chemokine CXCL13 was proposed as a possible marker for a more severe disease course and conversion from clinically isolated syndrome (CIS) to relapsing–remitting MS (RRMS).

Objective:

To investigate whether there are genetic susceptibility variants in MS that correlate with the levels of CXCL13 present in the CSF of MS patients.

Methods:

We genotyped the human leukocyte antigens HLA-DRB1 and HLA-A, plus a panel of single nucleotide polymorphisms (SNPs) that have been associated with susceptibility to MS and then correlated the genotypes with the levels of CXCL13, as measured with ELISA in the CSF of a total of 663 patients with MS, CIS, other neurological diseases (OND) or OND with an inflammatory component (iOND).

Results:

Presence of the HLA-DRB1*15 and the MS risk genotypes for SNPs in the RGS1, IRF5 and OLIG3/TNFAIP3 gene regions correlated significantly with increased levels of CXCL13.

Conclusion:

Our results pointed towards a genetic predisposition for increased CXCL13 levels, which in MS patients correlates with the severity of the disease course. These findings encourage further investigation and replication, in an independent patient cohort.
Using the Modified Checklist for Autism in Toddlers in a well-child clinic in Turkey: Adapting the screening method based on culture and setting
Authors: Kara Bülent , Mukaddes Nahit Motavalli , Altınkaya Işılay , Güntepe Dilek , Gökçay Gülbin , Özmen Meral
Published: November 2012

We aimed to adapt the Modified Checklist for Autism in Toddlers to Turkish culture. The Modified Checklist for Autism in Toddlers was filled out independently by 191 parents while they were waiting for the well-child examination of their child. A high screen-positive rate was found. Because of this high false-positive rate, a second study was done in which the Modified Checklist for Autism in Toddlers was administered by health-care staff in a short interview with two groups of parents. The first group (the high-risk group) comprised 80 children aged 18–36 months, who were initially diagnosed with pervasive developmental disorders. The second group (the low-risk group) comprised 538 children of the same age, who were followed regularly by the well-child clinic. Two screen positives were found in the low-risk group. These two children, a random sample of 120 children from the low-risk group, and all the high-risk group were invited to a clinical evaluation. The diagnostic power of the Modified Checklist for Autism in Toddlers was assessed against clinical diagnosis and the Childhood Autism Rating Scale. The positive predictive value of the Modified Checklist for Autism in Toddlers was found to be 75%. Our findings led us to conclude that the Modified Checklist for Autism in Toddlers is a useful tool in Turkey for screening of pervasive developmental disorders in primary care, but in our culture, it is completed more accurately when health-care personnel ask the parents the questions. This study shows that Modified Checklist for Autism in Toddlers screening should be adapted based on culture and setting.
Animating streamlines with orthogonal advancing waves
Authors: Yeh Chih-Kuo , Liu Zhanping , Kao David L , Lee Tong-Yee
Published: November 2012

Self-animating image of flow through repeated asymmetric patterns (RAPs) is an innovative approach for creating illusory motion using a single image. In this paper, we present a smooth cyclic variable-speed RAP animation model that emulates orthogonal advancing waves from a geometry-based flow representation. It enables dense, accurate visualization of complex real-world flows using animated streamlines of an elegant placement coupled with visually appealing orthogonal advancing waves. The animation model first performs velocity (magnitude) integral luminance transition on individual streamlines. Then, inter-streamline synchronization in luminance varying along the tangential direction is imposed. Next, tangential flow streaks are constructed using evenly spaced hue differing in the orthogonal direction. In addition, an energy-decreasing strategy is proposed that adopts an iterative yet efficient procedure for determining the luminance phase and hue of each streamline in HSL (hue, saturation, and lightness or brightness) color space. To increase the contrast between flow streaks, adaptive luminance interleaving in the direction perpendicular to the flow is further applied. We demonstrate the effectiveness of the animation model using some synthetic and real flows. Color figures, images, and accompanying animations are available at http://graphics.csie.ncku.edu.tw/flowvis .
Mental Health Promotion in a School Community by Using the Results From the Well-Being Profile
Authors: Puolakka Kristiina , Haapasalo-Pesu Kirsi-Maria , Konu Anne , Åstedt-Kurki Päivi , Paavilainen Eija
Published: November 2012

This article presents an action research project as a method to combine science and practical expertise in order to develop the practices of the health care system. The project aimed at developing mental health promotion in the school community in general and at finding tools for timely help when mental health is at risk. The underlying idea is that mental health is an integral part of health and by promoting general well-being it is also possible to promote and ensure mental health at school. The study was conducted in a Finnish lower secondary school of 446 pupils where the pupils are aged between 12 and 15 years. The initial survey was conducted using the School Well-being Profile, a tool developed by Anne Konu. A well-being questionnaire was used to identify the areas in need of improvement, providing the basis for planning and implementing development measures together with the local actors. The instrument proved to be a usable way of collecting feedback of the well-being of the school environment. As a result of the action research project, the school’s physical conditions and social relationships improved and appropriate practices for future problem situations were set.
Inmates’ Perceptions of the Benefits and Harm of Prison Interviews
Authors: Copes Heith , Hochstetler Andy , Brown Anastasia
Published: November 2012

We report here on inmates’ experiences with participating in interview-based research to provide insights on the ethics and validity of research on prisoners. We interviewed 40 inmates to explore their reasons for participating in previous research, the benefits and harm they experienced, and whether they felt coerced into participation. Inmates report several benefits from participating in research, including psychological satisfactions, a respite from the boredom of prison life, and monetary gain. Participants stated that they did not experience harm from the research or feel coerced to take part.
Numerical study of airflow and heat transfer in an air-cooled room with different inlet positions
Authors: Rodríguez Norma A , Hinojosa Jesús F
Published: November 2012

This study is focused to airflow and heat transfer analyses in an air-cooled room. Three-dimensional numerical results of a rectangular room considering three different inlet configurations are presented. The study was carried out considering turbulent flow and the radiative exchange between the walls. A vertical wall receives a constant heat flux, and the opposite wall is maintained at a uniform and constant temperature; the remaining walls are adiabatic. The air inlet velocity was 0.5 m/s and the emissivity of the walls was considered as 0.8. The mathematical model was solved numerically with Computational Fluid Dynamics software. The temperature fields, flow patterns, heat transfer coefficients, and temperature distribution effectiveness are presented and discussed. It was found that the heat transfer due to the radiative effect is around 50% for the three cases studied; besides, the heat transfer coefficients and temperature distribution effectiveness are highly dependent on the inlet position.
Avanafil for the treatment of erectile dysfunction: initial data and clinical key properties
Authors: Kedia George T. , Ückert Stefan , Assadi-Pour Farhang , Kuczyk Markus A. , Albrecht Knut
Published: November 2012

Orally active, selective inhibitors of phosphodiesterase type 5 (PDE 5, cyclic GMP PDE), such as sildenafil, tadalafil and vardenafil, are currently the first-choice treatment options for the clinical management of erectile dysfunction (ED) of various etiologies and severities. However, a significant number of patients remain dissatisfied with the available therapies due a lack of efficacy or discomfort arising from adverse events. Several new PDE5 inhibitors, among which are avanafil (TA-1790), lodenafil, mirodenafil, udenafil, SLX-2101, JNJ-10280205 and JNJ-10287069, have recently been approved and introduced into the market or are in the final stages of their clinical development. Avanafil (marketed in the US under the brand name STENDRA™) has been developed by VIVUS Inc. (Mountain View, CA, USA) and has recently received approval from the US Food and Drug Administration (FDA) for use in the treatment of male ED. The drug has demonstrated improved selectivity for PDE5, is rapidly absorbed after oral administration with a fast onset of action and a plasma half-life that is comparable to sildenfil and vardenafil. In phase II and phase III clinical trials that included a large number of patients, avanafil has been shown to be effective and well tolerated. Owing to its favorable pharmacodynamic and pharmacokinetic profile, avanafil is considered as a promising new option in the treatment of ED. The present article summarizes the initial data and clinical key properties of avanafil.
Clinical drug resistance linked to interconvertible phenotypic and functional states of tumor-propagating cells in multiple myeloma
Authors: Chaidos Aristeidis , Barnes Chris P. , Cowan Gillian , May Philippa C. , Melo Valeria , Hatjiharissi Evdoxia , Papaioannou Maria , Harrington Heather , Doolittle Helen , Terpos Evangelos , Dimopoulos Meletios , Abdalla Saad , Yarranton Helen , Naresh Kikkeri , Foroni Letizia , Reid Alistair , Rahemtulla Amin , Stumpf Michael , Roberts Irene , Karadimitris Anastasios
Published: November 2012

The phenotype and function of cells enriched in tumor-propagating activity and their relationship to the phenotypic architecture in multiple myeloma (MM) are controversial. Here, in a cohort of 30 patients, we show that MM composes 4 hierarchically organized, clonally related subpopulations, which, although phenotypically distinct, share the same oncogenic chromosomal abnormalities as well as immunoglobulin heavy chain complementarity region 3 area sequence. Assessed in xenograft assays, myeloma-propagating activity is the exclusive property of a population characterized by its ability for bidirectional transition between the dominant CD19−CD138+ plasma cell (PC) and a low frequency CD19−CD138− subpopulation (termed Pre-PC); in addition, Pre-PCs are more quiescent and unlike PCs, are primarily localized at extramedullary sites. As shown by gene expression profiling, compared with PCs, Pre-PCs are enriched in epigenetic regulators, suggesting that epigenetic plasticity underpins the phenotypic diversification of myeloma-propagating cells. Prospective assessment in paired, pretreatment, and posttreatment bone marrow samples shows that Pre-PCs are up to 300-fold more drug-resistant than PCs. Thus, clinical drug resistance in MM is linked to reversible, bidirectional phenotypic transition of myeloma-propagating cells. These novel biologic insights have important clinical implications in relation to assessment of minimal residual disease and development of alternative therapeutic strategies in MM.
Structural framework of c-Src activation by integrin β3
Authors: Xiao Run , Xi Xiao-Dong , Chen Zhu , Chen Sai-Juan , Meng Guoyu
Published: November 2012

The integrin β3-mediated c-Src priming and activation, via the SH3 domain, is consistently associated with diseases, such as the formation of thrombosis and the migration of tumor cells. Conventionally, activation of c-Src is often induced by the binding of proline-rich sequences to its SH3 domain. Instead, integrin β3 uses R760GT762 for priming and activation. Because of the lack of structural information, it is not clear where RGT will bind to SH3, and under what mechanism this interaction can prime/activate c-Src. In this study, we present a 2.0-Å x-ray crystal structure in which SH3 is complexed with the RGT peptide. The binding site lies in the “N”-Src loop of the SH3 domain. Structure-based site-directed mutagenesis showed that perturbation on the “N”-Src loop disrupts the interaction between the SH3 domain and the RGT peptide. Furthermore, the simulated c-Src:β3 complex based on the crystal structure of SH3:RGT suggests that the binding of the RGT peptide might disrupt the intramolecular interaction between the SH3 and linker domains, leading to the disengagement of Trp260:“C”-helix and further activation of c-Src.
Small RNA and transcriptome deep sequencing proffers insight into floral gene regulation in Rosa cultivars
Authors: Kim Jungeun , Park June Hyun , Lim Chan Ju , Lim Jae Yun , Ryu Jee-Youn , Lee Bong-Woo , Choi Jae-Pil , Kim Woong Bom , Lee Ha Yeon , Choi Yourim , Kim Donghyun , Hur Cheol-Goo , Kim Sukweon , Noh Yoo-Sun , Shin Chanseok , Kwon Suk-Yoon
Published: November 2012

Background

Roses (Rosa sp.), which belong to the family Rosaceae, are the most economically important ornamental plants—making up 30% of the floriculture market. However, given high demand for roses, rose breeding programs are limited in molecular resources which can greatly enhance and speed breeding efforts. A better understanding of important genes that contribute to important floral development and desired phenotypes will lead to improved rose cultivars. For this study, we analyzed rose miRNAs and the rose flower transcriptome in order to generate a database to expound upon current knowledge regarding regulation of important floral characteristics. A rose genetic database will enable comprehensive analysis of gene expression and regulation via miRNA among different Rosa cultivars.

Results

We produced more than 0.5 million reads from expressed sequences, totalling more than 110 million bp. From these, we generated 35,657, 31,434, 34,725, and 39,722 flower unigenes from Rosa hybrid: ‘Vital’, ‘Maroussia’, and ‘Sympathy’ and Rosa rugosa Thunb. , respectively. The unigenes were assigned functional annotations, domains, metabolic pathways, Gene Ontology (GO) terms, Plant Ontology (PO) terms, and MIPS Functional Catalogue (FunCat) terms. Rose flower transcripts were compared with genes from whole genome sequences of Rosaceae members (apple, strawberry, and peach) and grape. We also produced approximately 40 million small RNA reads from flower tissue for Rosa, representing 267 unique miRNA tags. Among identified miRNAs, 25 of them were novel and 242 of them were conserved miRNAs. Statistical analyses of miRNA profiles revealed both shared and species-specific miRNAs, which presumably effect flower development and phenotypes.

Conclusions

In this study, we constructed a Rose miRNA and transcriptome database, and we analyzed the miRNAs and transcriptome generated from the flower tissues of four Rosa cultivars. The database provides a comprehensive genetic resource which can be used to better understand rose flower development and to identify candidate genes for important phenotypes.
Concerted suppression of all starch branching enzyme genes in barley produces amylose-only starch granules
Authors: Carciofi Massimiliano , Blennow Andreas , Jensen Susanne L , Shaik Shahnoor S , Henriksen Anette , Buléon Alain , Holm Preben B , Hebelstrup Kim H
Published: November 2012

Background

Starch is stored in higher plants as granules composed of semi-crystalline amylopectin and amorphous amylose. Starch granules provide energy for the plant during dark periods and for germination of seeds and tubers. Dietary starch is also a highly glycemic carbohydrate being degraded to glucose and rapidly absorbed in the small intestine. But a portion of dietary starch, termed “resistant starch” (RS) escapes digestion and reaches the large intestine, where it is fermented by colonic bacteria producing short chain fatty acids (SCFA) which are linked to several health benefits. The RS is preferentially derived from amylose, which can be increased by suppressing amylopectin synthesis by silencing of starch branching enzymes (SBEs). However all the previous works attempting the production of high RS crops resulted in only partly increased amylose-content and/or significant yield loss.

Results

In this study we invented a new method for silencing of multiple genes. Using a chimeric RNAi hairpin we simultaneously suppressed all genes coding for starch branching enzymes (SBE I, SBE IIa, SBE IIb) in barley (Hordeum vulgare L.), resulting in production of amylose-only starch granules in the endosperm. This trait was segregating 3:1. Amylose-only starch granules were irregularly shaped and showed peculiar thermal properties and crystallinity. Transgenic lines retained high-yield possibly due to a pleiotropic upregualtion of other starch biosynthetic genes compensating the SBEs loss. For gelatinized starch, a very high content of RS (65 %) was observed, which is 2.2-fold higher than control (29%). The amylose-only grains germinated with same frequency as control grains. However, initial growth was delayed in young plants.

Conclusions

This is the first time that pure amylose has been generated with high yield in a living organism. This was achieved by a new method of simultaneous suppression of the entire complement of genes encoding starch branching enzymes. We demonstrate that amylopectin is not essential for starch granule crystallinity and integrity. However the slower initial growth of shoots from amylose-only grains may be due to an important physiological role played by amylopectin ordered crystallinity for rapid starch remobilization explaining the broad conservation in the plant kingdom of the amylopectin structure.
Green tea consumption and risk of esophageal cancer: a meta-analysis of epidemiologic studies
Authors: Zheng Ping , Zheng Hai-ming , Deng Xing-ming , Zhang Yang-de
Published: November 2012

Background

Green tea has shown the role of chemoprevention for cancer. Recently, several studies suggested that green tea intake may have effect on esophageal cancer risk, whereas the results were inconsistent.

Methods

We performed a meta-analysis of all English and Chinese language studies of green tea consumption and esophageal cancer risk indexed in Medline, Embase, the Science Citation Index, the Chinese Biomedical Database and Wanfang Data from 1980 to June 2012. After reviewing each study, extracting data, and evaluating heterogeneity (Chi-square-based Q test and Ι2) and publication bias (Begg and Egger test), a meta-analysis was performed to evaluate the association between high/medium/low green tea consumption and non-drinking esophageal cancer risk. Pooled relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs) were calculated using the fixed- or random-effect models.

Results

Ten eligible epidemiologic studies including 33731 participants and 3557 cases for esophageal cancer were included. Eight of which were case–control studies, and two were cohort studies. Overall, there were no association between high/medium/low green tea consumption and non-drinking risk of esophageal cancer (High: highest vs non-drinker: RR/OR = 0.76, 95% CI: 0.49 to 1.02. Medium: drinker vs non-drinker: RR/OR = 0.86, 95% CI: 0.70 to 1.03. Low: lowest vs non-drinker: RR/OR = 0.83, 95% CI: 0.58 to 1.08). When stratified analyses according to study design (case–control and cohort studies), country (China and Japan), participates source (population-based and hospital-based case–control), and gender (female and male), there were significant association between high/medium/low green tea consumption and non-drinking risk of esophageal cancer among female (High: RR/OR = 0.32, 95% CI: 0.10 to 0.54. Medium: RR/OR = 0.43, 95% CI: 0.21 to 0.66. Low: RR/OR = 0.45, 95% CI: 0.10 to 0.79), but not the others.

Conclusions

We did not found significant association between green tea consumption and non-drinking esophageal cancer risk, but an evidence of protective effect was observed among female.
Renal AA-amyloidosis in intravenous drug users – a role for HIV-infection?
Authors: Jung Oliver , Haack Hans Stefan , Buettner Maike , Betz Christoph , Stephan Christoph , Gruetzmacher Peter , Amann Kerstin , Bickel Markus
Published: November 2012

Background

Chronic renal disease is a serious complication of long-term intravenous drug use (IVDU). Recent reports have postulated a changing pattern of underlying nephropathy over the last decades.

Methods

Retrospective investigation including all patients with prior or present IVDU that underwent renal biopsy because of chronic kidney disease between 01.04.2002 and 31.03.2012 in the city of Frankfurt/Main, Germany.

Results

Twenty four patients with IVDU underwent renal biopsy because of progressive chronic kidney disease or proteinuria. Renal AA-amyloidosis was the predominant cause of renal failure in 50% of patients. Membranoproliferative glomerulonephritis (GN) was the second most common cause found in 21%. Patients with AA-amyloidosis were more likely to be HIV infected (67 vs.17%; p=0.036) and tended to have a higher rate of repeated systemic infections (92 vs. 50%; p=0.069). Patients with AA-amyloidosis presented with progressive renal disease and nephrotic-range proteinuria but most patients had no peripheral edema or systemic hypertension. Development of proteinuria preceded the decline of GFR for approximately 1–2 years.

Conclusions

AA-amyloidosis was the predominant cause of progressive renal disease in the last 10 years in patients with IVDU. The highest rate of AA-amyloidosis observed was seen in HIV infected patients with IVDU. We speculate that chronic HIV-infection as well as the associated immunosuppression might promote development of AA-amyloidosis by increasing frequency and duration of infections acquired by IVDU.
Acute symptomatic hypoglycaemia mimicking ischaemic stroke on imaging: a systemic review
Authors: Yong Ai Wain , Morris Zoe , Shuler Kirsten , Smith Colin , Wardlaw Joanna
Published: November 2012

Background

Acute symptomatic hypoglycaemia is a differential diagnosis in patients presenting with stroke-like neurological impairment, but few textbooks describe the full brain imaging appearances. We systematically reviewed the literature to identify how often hypoglycaemia may mimic ischaemic stroke on imaging, common patterns and relationships with hypoglycaemia severity, duration, clinical outcome and add two new cases.

Methods

We searched EMBASE and Medline databases for papers reporting imaging in adults with symptomatic hypoglycaemia. We analysed the clinical presentation, outcome, brain imaging findings, duration and severity of hypoglycaemia, time course of lesion appearance, including two new cases.

Results

We found 42 papers describing computed tomography or magnetic resonance imaging in 65 patients, plus our two cases with symptomatic hypoglycaemia. Imaging abnormalities on computed tomography and magnetic resonance were uni or bilateral, cortical or sub-cortical. Thirteen (20%) mimicked cortical or lacunar stroke. Acute lesions had restricted diffusion on magnetic resonance or low attenuation on computed tomography, plus swelling; older lesions showed focal atrophy or disappeared, as with ischaemic stroke. The association between the depth or duration of hypoglycaemia, the severity or extent of neurological deficit, and the imaging abnormalities, was weak.

Conclusion

Imaging abnormalities in patients with hypoglycaemia are uncommon but very variable, weakly associated with neurological deficit, and about a fifth mimic acute ischaemic stroke. Blood glucose testing should be routine in all patients with acute neurological impairment and hypoglycaemia should be included in the differential diagnosis of imaging appearances in patients presenting with acute stroke.
Minocycline-associated rimmed vacuolar myopathy in a patient with rheumatoid arthritis
Authors: Bokuda Kota , Sugaya Keizo , Tamura Shunichiro , Miyamoto Kazuhito , Matsubara Shiro , Komori Takashi
Published: November 2012

Background

The autophagic vacuolar myopathies (AVM) are a group of inherited myopathies defined by the presence of autophagic vacuoles in pathological muscle specimens. AVM can be categorized into three groups: acid maltase deficiency, myopathies characterized by autophagic vacuoles with unique sarcolemmal features, and rimmed vacuolar myopathies (RVM). While the pathogeneses of these conditions are still being elucidated, some drugs (e.g., chloroquine, its analog, hydroxychloroquine, and colchicine) can also cause AVM. Minocycline is a disease-modifying anti-rheumatic drug that may be used in the treatment of rheumatoid arthritis (RA). Here, we describe the first case of minocycline-associated AVM with rimmed vacuole formation.

Case presentation

A 75-year-old woman suffering from RA has been continuously treated with minocycline (200 mg/day) for the past 7 years. During this time, she developed a myopathy that predominantly affected her lower limbs. Histological studies of biopsied muscle revealed scattered atrophic myofibers with rimmed vacuoles that contained pigment granules. Histochemical staining revealed that the pigment comprised both iron and melanin, which is consistent with type II minocycline-induced cutaneous pigmentation. Under electron microscopy, autophagic vacuoles were consistently observed in association with numerous collections of pigment granules.

Conclusions

This is the first report of minocycline-induced pigmentation in skeletal muscle. The strong association between autophagic vacuoles and the accumulation of minocycline-induced pigments suggest that long-term minocycline treatment induced pigment accumulation, leading to elevation of autophagic activity and RVM. It might also be possible that minocycline directly activated autophagy, as the observed pigments are known to form complexes containing minocycline and/or its metabolites. As long-term minocycline treatment is expected to be used more widely in the future, we must draw attention to this adverse effect.