bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards the comprehensive and systematic assessment of the adaptive reuse of Islamic architectural heritage in Cairo
Authors: Shehata Waleed Tarek Ali , Moustafa Yasser , Sherif Lobna , Botros Ashraf
Published: May 2015

Purpose

– Many of the heritage adaptive reuse projects in Islamic Cairo did not report success. Existing evaluations are usually drawn from a singular perspective – such as preservation and sustainability. The purpose of this paper is to generate a comprehensive assessment framework of adaptively reused heritage buildings that is specifically developed for the case of Islamic heritage of Cairo.

Design/methodology/approach

– This paper depends on an extensive literature review about primary goals of adapting heritage for reuse. Related to each goal, multiple criteria of assessment are derived from literature, and then explained to mention worldwide benchmarks in that field.

Findings

– A successful heritage adaptation project shall aim to achieve: building preservation, success of new function, and local community development. The framework is able to organize the adaptive reuse literature in general, and to specifically provide direct goals and guidelines in the case of Cairo.

Research limitations/implications

– In research and practice, priorities of heritage reuse vary from case-to case; however, this paper considers all assessment criteria to be of equal importance.

Practical implications

– In order to apply and technically develop this assessment framework, future research can describe methodologies for assessment and to set optimum quantitative and/or qualitative indicators’ thresholds for each criterion.

Social implications

– This paper highlights that new uses of heritage buildings should be assessed for having a role in the upgrading the socio-economic milieu of the people living. The new functions shall act as a stimulant for economic upraising and social reinforcement for the local business and small traditional industries.

Originality/value

– The framework can be used as a checklist in either the planning of adaptive reuse projects or the evaluation of already completed ones. The framework shall assist governmental institutions, developers, owners, community groups, practitioners, and others in bringing forward successful adaptation schemes in Cairo.
Dynamic integrity: a concept to historic urban landscape
Authors: Mendes Zancheti Silvio , Piccolo Loretto Rosane
Published: May 2015

Purpose

– The purpose of this paper is to set out a proposal for the concept of dynamic integrity. It is a heritage quality that may be attributed to heritage properties whose attributes are capable to express past and present meanings, and therefore values, in a context of change, without relying exclusively on records of memory. So, dynamic integrity (DI) emphasizes continuity in changing urban context and may be a key concept for the new Historic Urban Landscape (HUL) approach.

Design/methodology/approach

– The concept of DI was developed using theory of complexity to critic the existing definitions of integrity and their use to in context of urban heritage area under the pressure for change.

Findings

– The current concept of integrity, adopted by heritage field of knowledge, is not capable to deal with the complexity of the HUL. There is a tendency to define conservation as the regulation or control of change. This assumption is problematic since it emphasizes the changes of meanings, values and attributes, instead of the idea of continuity. Controlling change means fixing the attributes that express the meanings of heritage areas, and this is a task fated to be unsuccessful in complex cities or, even in not so complex urban sites.

Originality/value

– It is the first time that the concept of integrity has been put to explain and manage the dynamics of urban heritage areas.
Ecomuseum, community museology, local distinctiveness, Hüsamettindere village, Bogatepe village, Turkey
Authors: Dogan Mustafa
Published: May 2015

Purpose

– The concept of sustainable development is now widely accepted as a means of protecting natural resources and cultural heritage. One approach to ensuring sustainability, especially in relation to cultural tourism, is the ecomuseum. Turkey has considerable potential to develop ecomuseological models to encourage local sustainable development. The purpose of this paper is to explore the development of ecomuseums in Turkey by analysing the recent implementation of the concept in Hüsamettindere and Bogatepe villages. Current practices at these two sites are evaluated in comparison with the basic principles of ecomuseum theory.

Design/methodology/approach

– This paper explores local community involvement in two emerging ecomuseums in Turkey based on several years of participant action research by the author; it describes the nature of the two ecomuseums based on that experience. In addition an in-depth survey was carried out between February and April 2013 by Canakkale Onsekiz Mart University when 45 local participants were interviewed for their views on the ecomuseum developments, using the MACDAB method (Borrelli et al., 2008) as a guide.

Findings

– Even though the two implementations in Turkey have different features deriving from their local dynamics, they have had a similar experience in terms of the development process. Both began with a volunteer movement, the organisation of the local community, the formation of civil initiatives, a joint decision-making processes and the existence of participation and consensus. This process conforms to the basic principles of ecomuseology. The ecomuseums have also raised concerns about the loss of rural heritage and the mechanisms for conserving it within the model of the “living” ecomuseum. The most significant fact to emerge from this initial review of the two ecomuseums is that it is not necessarily their ability to conserve fragments of tangible and intangible heritage that is paramount in Turkey, but their importance in providing employment opportunities in rural areas.

Originality/value

– Ecomuseum movement is a very important and practical model for sustainable development and tourism. Ecomuseums can also be functional tools for protecting of cultural heritage and developing of local areas. Even though Turkey has got many cultural heritage sources, they are not used productively for local sustainable development. The two implementations will be sample to all natural and cultural heritage areas of Turkey for sustainable development.
A model for the diffusion of knowledge sharing technologies inside private transport companies
Authors: Del Giudice Manlio , Della Peruta Maria Rosaria , Maggioni Vincenzo
Published: May 2015

Purpose

– This paper aims to investigate, inside the private sector of transport, a model for the diffusion of knowledge-sharing technologies with non-uniform internal influence that has been developed by Easingwoodet al.(1983).

Design/methodology/approach

– The authors performed an empirical evaluation of the performances of the model by Easingwoodet al.(1983) by analyzing data gathered from almost 230 taxi drivers joining two of the biggest taxi brokers operating in the Southern Italian city of Naples.

Findings

– Such an analysis reveals that the model by Easingwoodet al.(1983) provides an excellent agreement with the empirical data and allows to obtain interesting predictions on the future evolution of the sector performances in terms of increasing use of knowledge-sharing technologies within the taxi drivers’ community of practice (CoP).

Research limitations/implications

– In particular, the authors show that a unique solution always exists, which is defined on the whole (positive) set of times and, in the long run, tends to a steady-state equilibrium. A first limit of the present research is certainly the use of a sample restricted to the taxi companies from only one city: future investigations should consider a larger sample by interviewing taxi companies from multiple regions as well. Another limit is that the model performed does not take into account all the factors influencing the diffusion of knowledge-sharing technologies within the CoP. Finally, the research design is not considering the impact of the diffusion of knowledge-sharing technologies on the customer relationship management.

Originality/value

– The research shows the application of a valid model both for evaluating the diffusion of technologies for sharing knowledge within a CoP and for estimating its development trend. It represents the first original study in Italy that empirically investigates the diffusion of technological innovations for the knowledge management in an industry typically dominated by tacit codes of knowledge-sharing: the taxi companies.
Public sector knowledge management: a structured literature review
Authors: Massaro Maurizio , Dumay John , Garlatti Andrea
Published: May 2015

Purpose

– This paper aims to review and critique the public sector knowledge management (KM) literature, offers an overview of the state of public sector KM research and outlines a future research agenda.

Design/methodology/approach

– Articles published in KM journals are analyzed using a structured literature review methodology. The paper analyzes 180 papers published within ten journals specializing in the field of KM.

Findings

– Public sector KM is a research area of growing importance. Findings show that few authors specialize in the field and there are several obstacles to developing a cohesive body of literature. Low levels of international cooperation among authors and international comparisons mean that the literature is fragmented. Some research topics and some geographical areas within the public sector theme are over-analyzed, while others are under-investigated. Additionally, academic researchers should re-think their methodological approach if they wish to make significant contributions to the literature and work toward developing research which impacts practice in conjunction with practitioners.

Originality/value

– The paper presents a comprehensive structured literature review of the articles published in KM journals. The paper’s findings can offer insights into future research needs.
Understanding “disengagement from knowledge sharing”: engagement theory versus adaptive cost theory
Authors: Ford Dianne , Myrden Susan E. , Jones Tim D
Published: May 2015

Purpose

– The purpose of this paper is using competing hypotheses (a spillover hypothesis, based on Engagement Theory, and a provisioning hypothesis, based on Adaptive Cost Theory) to help explain why employees become disengaged from knowledge sharing.

Design/methodology/approach

– Employed knowledge workers completed an online questionnaire regarding their job characteristics, their general health and wellness, perceived organizational support, job engagement and disengagement from knowledge sharing.

Findings

– The findings provide empirical support for Adaptive Cost Theory and illustrate the relationship between Engagement Theory and the Disengagement from Knowledge Sharing. In particular, this research illustrates the importance of health and wellness for preventing disengagement from knowledge sharing. In addition, the findings introduce a new finding of tensions between job engagement and knowledge sharing, which supports knowledge workers’ complaints of “being too busy” to share.

Research limitations/implications

– This study uses cross-sectional methodology; however, the participants are employed and in the field. Given the theoretical arguments that disengagement from knowledge sharing should be either short term or transient, future research should follow-up with diary methods to capture this to confirm the study’s conclusions.

Practical implications

– The findings of this study provide some insight for practitioners on how to prevent disengagement from knowledge sharing. New predictors and an interesting tension between job engagement and knowledge sharing are identified.

Originality/value

– This study examines an alternative explanation for the lack of knowledge sharing in organizations, and uses competing theories to identify the reasons for the disengagement from knowledge sharing.
Can soap be a sustainable alternative to petroleum-based thermal insulation?
Authors: Read Lee , Arayici Yusuf
Published: May 2015

Purpose

– Thermal insulation is important to achieve energy efficiency in a buildings’ lifespan while maintaining comfort. Traditionally, the majority of insulation in buildings is man-made petroleum based products with limited or no-end life usage. However, from an environmental and economic sustainability perspective, they are not sustainable as natural resources are finite and in danger of run-out. Furthermore, they are also highly influenced by the increasing price and the ongoing scarcity of fossil fuel oils. The paper aims to discuss these issues.

Design/methodology/approach

– This paper introduces soap based insulation from recycled materials as a sustainable alternative to petroleum counterparts. The methodology is lab based experimentation and iterative tests. The phased based research process for the incremental development of the soap based thermal insulation is explained.

Findings

– Findings reveal that soap based insulation can be one possible way forward in the quest for natural and sustainable thermal insulation from recycled products to preserve and conserve the sustainable environment.

Originality/value

– Thus, the paper provides a unique environmentally friendly approach as an alternative to those existing petroleum counterparts for thermal insulation in buildings.
Turning building renovation measures into energy saving opportunities
Authors: Gohardani Navid , Af Klintberg Tord , Björk Folke
Published: May 2015

Purpose

– The purpose of this paper is to promote energy saving measures concurrent with major planned renovation/refurbishment in residential buildings.

Design/methodology/approach

– The methodology comprises of case studies, in which the influence of various factors is identified on the overall decision making related to building renovation/refurbishment.

Findings

– The employed operational decision support process enables energy saving opportunities for residential buildings in conjunction with planned major renovations/refurbishments.

Research limitations/implications

– The research scope is confined to residential buildings in Sweden and cooperatives with tenants as the owners and governors.

Practical implications

– A novel approach to synergistic energy saving and renovation in residential buildings is exhibited.

Social implications

– The paper presents an altered viewpoint of energy renovation means for residential buildings in the built environment.

Originality/value

– The paper presents a novel approach for building owners to renovate a building in terms of improved performance, energy efficiency and indoor comfort in combination with planned renovations/refurbishments.
The Role of Strategic Agility in Acquisitions
Authors: Junni Paulina , Sarala Riikka M. , Tarba Shlomo Y. , Weber Yaakov
Published: May 2015

The aim of the present study is to examine the role of strategic agility as a component of the acquisition process by investigating its constituent elements and effects on knowledge transfer in the context of acquisitions. The study also elaborates on the relationship between knowledge transfer and performance in acquisitions. We test our theoretical model on a quantitative data set of acquisitions conducted by Finnish companies.
The Struggle for Strategy: On the Politics of the Basic Income Proposal
Authors: De Wispelaere Jurgen
Published: May 2015

Policy interest in the basic income (BI) proposal is booming, but remarkably little attention is spent on systematically examining political strategies to build robust enabling coalitions in favour of BI. This article reviews two thorny problems that affect the coalition-building efforts of BI advocates: the problem of cheap political support suggests most BI support may be of little value to further its implementation, while the problem of persistent political division argues superficial agreement among committed BI advocates may mask persistent disagreement on which precise model to adopt. The article discusses the relevance of each of these problems for BI politics, employing both analytical arguments and brief illustrations taken from debates in various countries.
Altered profile of serum microRNAs in pancreatic cancer‐associated new‐onset diabetes mellitus
Authors: Dai Xin , Pang Wenjing , Zhou Yufeng , Yao Weiyan , Xia Lu , Wang Cheng , Chen Xi , Zen Ke , Zhang Chen‐Yu , Yuan Yaozong
Published: May 2015

Background

New‐onset diabetes mellitus in pancreatic cancer has been recognized as a paraneoplastic phenomenon caused by the existence of the tumor. Circulating microRNAs (miRNAs) are emerging as non‐invasive biomarkers for the detection of various cancers. In the present study, we hypothesized that a specific serum miRNA profile exists in pancreatic cancer‐associated new‐onset diabetes mellitus (PaC‐DM).

Methods

Initial screening of differentially expressed miRNAs in pooled serum samples from 25 PaC‐DM patients, 25 non‐cancer new‐onset type 2 diabetes mellitus (T2DM) patients, and 25 healthy controls was performed by TaqMan low‐density arrays (TLDA). A stem–loop quantitative reverse transcription–polymerase chain reaction (qRT‐PCR) was conducted to confirm the relative concentrations of candidate miRNAs in 80 PaC‐DM, 85 non‐cancer new‐onset T2DM patients, and 80 healthy controls.

Results

The TLDA identified 16 serum miRNAs that were significantly increased in PaC‐DM samples. A combination of six serum miRNAs (miR‐483‐5p, miR‐19a, miR‐29a, miR‐20a, miR‐24, miR‐25) was selected by qRT‐PCR as a biomarker for PaC‐DM. The area under the receiver operating characteristic curve (AUC) for the six‐miRNA panel training and validation sets was 0.959 (95% confidence interval [CI] 0.890–1.028) and 0.902 (95% CI 0.844–0.955), respectively. The combination of these six miRNAs enabled the discrimination of PaC‐DM from non‐cancer new‐onset T2DM with an AUC of 0.885 (95% CI 0.784–0.986) and 0.887 (95% CI 0.823–0.952) for the training and validation sets, respectively.

Conclusion

The six‐serum miRNA panel may have potential as a biomarker for the accurate diagnosis and discrimination of PaC‐DM from healthy controls and non‐cancer new‐onset T2DM.
Efficacy and safety of nonsteroidal anti‐inflammatory drugs in Asian patients with knee osteoarthritis: summary of a randomized, placebo‐controlled study
Authors: Essex Margaret N. , O'Connell Michael A. , Behar Regina , Bao Weihang
Published: May 2015

Aim

To compare the efficacy, tolerability and safety of celecoxib, naproxen and placebo in Asian patients with osteoarthritis (OA) of the knee.

Method

Patients of Asian descent with knee OA, aged ≥ 45 years, in a flare state with a functional capacity classification of I–III, received celecoxib 200 mg once daily, naproxen 500 mg twice daily or placebo, for 6 weeks. The change in Patient's Assessment of Arthritis Pain (week 6 vs. baseline) was the primary endpoint. Secondary endpoints, including Patient's and Physician's Global Assessments of Arthritis, Western Ontario and McMaster Universities OA Index (WOMAC), use of complementary and alternative medicines, incidence of treatment‐emergent adverse events (TEAEs) and measurements of upper gastrointestinal tolerability, were also assessed.

Results

Three hundred and sixty‐seven patients were randomized: 145 to celecoxib, 144 to naproxen and 78 to placebo. Celecoxib was as effective as naproxen in reducing OA pain (least squares mean change from baseline in visual analogue scale score [standard error] −37.1 [2.0] for celecoxib and −37.5 [2.0] for naproxen). Patient's and Physician's Global Assessment of Arthritis, WOMAC scores, Pain Satisfaction Scale and Patient Health Questionnaire‐9 showed statistically significant improvement in active treatment groups versus placebo, with the exception of naproxen WOMAC scores. Treatment‐related TEAEs occurred in 19 (13%), 34 (24%) and six (8%) patients in the celecoxib, naproxen and placebo groups, respectively.

Conclusion

Celecoxib and naproxen were comparable in their effects to reduce the signs and symptoms of knee OA in Asian patients. Celecoxib was shown to be safe and well tolerated in this patient population.
Rad51 in regulating the radiosensitivity of non‐small cell lung cancer with different epidermal growth factor receptor mutation status
Authors: Zhong Xing , Luo Guomin , Zhou Xiaojuan , Luo Wen , Wu Xia , Zhong Renming , Wang Yanping , Xu Feng , Wang Jin
Published: May 2015

Background

Non‐small cell lung cancer (NSCLC) harboring kinase‐domain mutations in epidermal growth factor receptors (EGFR) has been observed to be sensitive to ionizing radiation (IR). We explore Rad51‐dependent homologous recombination (HR) DNA repair in regulating radiosensitivity in two NSCLC cell lines with different EGFR mutation status.

Methods

NSCLC cell lines, wild‐type EGFR A549 and mutant EGFR H820 with an in‐frame deletion in exon 19 of EGFR (ΔE746–E750), were cultured. Radiosensitivity was estimated by colony forming assay. Rad51 expression was evaluated by quantitative real time‐polymerase chain reaction and Western‐blot. Lentiviral small hairpin ribonucleic acid‐Rad51 and ΔE746–E750 deletion mutant EGFR were constructed and transfected into cells. Flowcytometry assay was used to analyze DNA double strand breaks, cell cycle alterations, and apoptosis.

Results

A549 had a higher survival factor (SF)2 (0.66 vs. 0.44) and lower α/β value (4.07 vs. 9.01). Compared with the A549 cell, the H820 cell exhibited defective arrest in the S‐phase, a higher rate of G2/M accumulation, early apoptosis, and residual γ‐H2AX. Downregulated Rad51 expression decreased SF2 (0.42 vs. 0.31) and increased the α/β ratio (7.51 vs. 10.5), G2/M accumulation, early apoptosis, and γ‐H2AX in two cell lines. H820 had a low IR‐induced Rad51 expression and nuclear translocation. Exogenous expression of the ΔE746–E750 deletion mutant EGFR caused the A549 cell to become more radiosensitive.

Conclusions

An EGFR mutated NSCLC cell line is sensitive to IR, which is correlated with reduced IR‐induced Rad51 expression and nuclear translocation. The signaling pathway of EGFR maintaining Rad51 protein levels maybe a novel lung cancer therapeutic target to overcome radioresistance.
Community composition and activity of insectivorous bats in Mediterranean olive farms
Authors: Herrera J. M. , Costa P. , Medinas D. , Marques J. T. , Mira A.
Published: May 2015

Olive (Olea europaea L.) farming is one of the most widespread agricultural practice throughout the Mediterranean basin. Current trends even predict an increase in land area devoted to olive farms as well as the intensification of farming practices. However, knowledge of the effects of olive farming on animal species still remains elusive and conservation and management guidelines for the relevant stakeholders are therefore urgently needed. Here, we investigate community composition and activity patterns of insectivorous bats in Mediterranean olive monocultures in Southern Portugal. Bats surveys were carried out in three types of olive farms representing increasing levels of management intensity: (1) traditional olive farms, managed with few or no chemical inputs or manual labor; (2) semi‐intensive olive farms, which share certain characteristics with traditional plantations, but are more intensively managed; (3) intensive olive farms, which are managed with high and frequent chemical inputs, and highly mechanized systems. We found differences in species richness and activity levels between farming practices. Both the number of species and foraging activity declined with increasing management intensity. However, olive groves as a whole showed a lower number of species compared with the regional species pool and extremely low activity levels, suggesting that large and homogeneous olive monocultures may serve more as commuting areas than true foraging habitats for bats. To our knowledge, this is the first study explicitly demonstrating the pervasive impact of olive farming on the community composition and activity levels of insectivorous bats. In the face of an even‐increasing proportion of land surface devoted to olive farming in Mediterranean landscapes, our findings are therefore of great concern. We suggest that increasing habitat heterogeneity would contribute to preserve the community composition and ecological functionality of insectivorous bats in extensive olive monocultures.
E‐cigarettes generate high levels of aldehydes only in ‘dry puff’ conditions
Authors: Farsalinos Konstantinos E. , Voudris Vassilis , Poulas Konstantinos
Published: May 2015

Background and aims

Aldehydes are emitted by electronic cigarettes due to thermal decomposition of liquid components. Although elevated levels have been reported with new‐generation high‐power devices, it is unclear whether they are relevant to true exposure of users (vapers) because overheating produces an unpleasant taste, called a dry puff, which vapers learn to avoid. The aim was to evaluate aldehyde emissions at different power levels associated with normal and dry puff conditions.

Design

Two customizable atomizers were prepared so that one (A1) had a double wick, resulting in high liquid supply and lower chance of overheating at high power levels, while the other (A2) was a conventional setup (single wick). Experienced vapers took 4‐s puffs at 6.5 watts (W), 7.5 W, 9 W and 10 W power levels with both atomizers and were asked to report whether dry puffs were generated. The atomizers were then attached to a smoking machine and aerosol was trapped.

Setting

Clinic office and analytical chemistry laboratory in Greece.

Participants

Seven experienced vapers.

Measurements

Aldehyde levels were measured in the aerosol.

Findings

All vapers identified dry puff conditions at 9 W and 10 W with A2. A1 did not lead to dry puffs at any power level. Minimal amounts of aldehydes per 10 puffs were found at all power levels with A1 (up to 11.3 µg for formaldehyde, 4.5 µg for acetaldehyde and 1.0 µg for acrolein) and at 6.5 W and 7.5 W with A2 (up to 3.7 µg for formaldehyde, 0.8 µg for acetaldehyde and 1.3 µg for acrolein). The levels were increased by 30 to 250 times in dry puff conditions (up to 344.6 µg for formaldehyde, 206.3 µg for acetaldehyde and 210.4 µg for acrolein, P < 0.001), while acetone was detected only in dry puff conditions (up to 22.5 µg).

Conclusions

Electronic cigarettes produce high levels of aldehyde only in dry puff conditions, in which the liquid overheats, causing a strong unpleasant taste that e‐cigarette users detect and avoid. Under normal vaping conditions aldehyde emissions are minimal, even in new‐generation high‐power e‐cigarettes.
Oral mucosal disease in an Australian urban Indigenous community using autofluorescence imaging and reflectance spectroscopy
Authors: Lalla Y , Matias MAT , Farah CS
Published: May 2015

Background

The aim of this study was to document the oral mucosal burden in an urban Indigenous community and to evaluate the efficacy of an adjunctive optical device (Identafi™) in a general dental practice.

Methods

Three hundred and forty‐two patients who presented to an urban Aboriginal and Torres Strait Islander Community Health Service (ATSICHS) were examined using conventional oral examination (COE) and with a multispectral device (Identafi™). Loss of autofluorescence (LAF) and the visibility of diffuse vasculature were noted.

Results

The urban Indigenous community assessed did not display significantly higher rates of smoking, alcohol consumption or lesion prevalence compared to non‐Indigenous counterparts. The white and violet light functions of Identafi™ provided excellent lesion visibility in 84.5% and 77.9% of cases respectively compared to 75% with COE, and were capable of highlighting new lesions not seen during COE.

Conclusions

The urban Indigenous community does not appear to display a significantly higher prevalence of risk factors such as smoking and alcohol consumption compared to their non‐Indigenous counterparts living in the same region, nor are they more likely to have oral mucosal lesions. The incidence of intraoral pigmentation has the potential to complicate use of autofluorescence screening devices, emphasizing the importance of skill and training when using this technology.
Exploration of the mechanisms of biofilm formation by Enterococcus faecalis in glucose starvation environments
Authors: Ran SJ , Jiang W , Zhu CL , Liang JP
Published: May 2015

Background

Enterococcus faecalis is the most common single species present in teeth after failed root canal therapy. This is mainly due to its ability to maintain viability for a long time in filled root canals where nutrients are normally sparse. The aim of this study was to explore the mechanism of E. faecalis survival and biofilm formation in glucose‐starved environments.

Methods

Enterococcus faecalis ATCC 33186 was inoculated in energy starvation media for biofilm formation. Confocal laser scanning microscopy and fluorescent DNA‐binding agents were employed to assess biofilm‐forming ability. The physiochemical properties of the biofilm cell wall were investigated by measuring the hydrophobicity, extracellular polysaccharide and ATPase activity. The expression of stress and virulence genes was quantified by real‐time quantitative polymerase chain reaction.

Results

The ability for biofilm formation decreased with a decreasing concentration of glucose. The cell surface hydrophobicity increased dramatically with decreasing glucose concentration. Water‐soluble exopolysaccharide (WSE) synthesis decreased in glucose starvation media, whereas water‐insoluble exopolysaccharide (WIE) synthesis increased. A marked decrease in ATPase activity was observed only in a no glucose medium. In addition, transcription of ace, fsrB and gelE genes increased under glucose starvation stress while atpE, salB and esp genes were down‐regulated.

Conclusions

Enterococcus faecalis survival and biofilm formation under glucose starvation stress may be attributed to an increase in cell‐surface hydrophobicity and additionally to the up‐regulation of some genes involved in stress response and biofilm formation. These characteristics may explain why E. faecalis can maintain viability for a long time in an energy‐starved environment and why it is frequently isolated from persistently infected root canals.
Diversity of Cervicovaginal Cytokine Response to Incident Chlamydia trachomatis Infection Among a Prospective Cohort of Young Women
Authors: Hwang Loris Y. , Scott Mark E. , Ma Yifei , Moscicki Anna‐Barbara
Published: May 2015

Problem

Animal, in vitro, and ex vivo studies have identified several cytokines involved in host immunity to genital Chlamydia trachomatis (CT) infection. However, in vivo cytokine responses are not well described. Our objectives were to document cervicovaginal cytokine levels and intrawoman cytokine changes during incident CT in a prospective cohort.

Methods

From our prospective cohort, 62 women had incident CT, comprising a CT‐negative visit followed by a CT‐positive visit. At these visits, cytokine protein levels (IL‐6, IL‐8, IL‐1α, IL‐1β, MIP‐1α, RANTES, IFN‐γ) were measured using cervicovaginal lavages and the MILLIPLEX™/Luminex® multiplex assay. Quartiles were defined for each cytokine from all 124 visits.

Results

At the group level, RANTES was higher (P < 0.01) at the CT‐positive visit than at baseline, but the other cytokines did not significantly differ. For intrawoman cytokine changes, women with a cytokine level that increased at least one quartile higher (going from baseline to the CT‐positive visit) ranged between 26 and 53%. Women with a cytokine level staying in the same quartile ranged between 32 and 48%. Women with a cytokine level that decreased at least one quartile lower ranged between 15 and 37%.

Conclusion

Intrawoman cervicovaginal cytokine changes during incident CT appear heterogeneous and may reflect differences in natural host immunity.
BAX and BCL‐2 polymorphisms, as predictors of proliferative vitreoretinopathy development in patients suffering retinal detachment: the Retina 4 project
Authors: Pastor‐Idoate Salvador , Rodríguez‐Hernández Irene , Rojas Jimena , Fernández Itziar , García‐Gutierrez María‐Teresa , Ruiz‐Moreno Jose M. , Rocha‐Sousa Amandio , Ramkissoon Yashin D. , Harsum Steven , MacLaren Robert E. , Charteris David G. , Van Meurs Jan C. , González‐Sarmiento Rogelio , Pastor Jose C. ,   the Genetics on PVR Study Group
Published: May 2015

Purpose

To compare the distribution of BCL‐2 ‐938C>A (rs2279115) and BAX ‐248G>A (rs4645878) genotypes among European subjects undergoing rhegmatogenous retinal detachment (RRD) surgery in relation to the further development of proliferative vitreoretinopathy (PVR).

Methods

A case–control gene association study, as a part of Retina 4 project, was designed. rs2279115 and rs4645878 polymorphisms were analysed in 555 samples from patients with RRD (134 with PVR secondary to surgery). Proportions of genotypes and AA homozygous groups of BCL‐2 and BAX polymorphisms between subsamples were analysed in two phases. Genotypic and allelic frequencies were compared in global sample and in subsamples.

Results

BAX: Differences were observed in the genotype frequencies and in AA carriers between controls and cases in the global series. The odds ratio (OR) of A carriers in the global sample was 1.7 (95% CI: 1.23–2.51). Proportions of genotypes in Spain + Portugal were significant different. The OR of A carriers from Spain and Portugal was 1.8 (95% CI: 1.11–2.95). BCL‐2: No significant differences were observed in genotype frequencies. However, proportions of genotypes in Spain + Portugal were significant. A protective effect (OR: 0.6 95% CI: 0.43–0.96) was found in A carriers from Spain and Portugal.

Conclusions

Results suggest that A allele of rs4645878 could be a biomarker of high risk of developing PVR in patients undergoing RD surgery. The possible role of BCL‐2 (inhibitor of necroptosis pathway) as a possible new target in PVR prophylaxis should be investigated.
Basophil activation by mosquito extracts in patients with hypersensitivity to mosquito bites
Authors: Sakakibara Yasuhisa , Wada Taizo , Muraoka Masahiro , Matsuda Yusuke , Toma Tomoko , Yachie Akihiro
Published: May 2015

Hypersensitivity to mosquito bites (HMB) is a cutaneous disorder belonging to the group of Epstein–Barr virus (EBV)‐associated T/natural killer (NK)‐cell lymphoproliferative diseases, and is primarily mediated by EBV‐infected NK cells. It is characterized by intense local skin reactions accompanied by general symptoms after mosquito bites, and infiltration of EBV‐infected NK cells into the bite sites. However, the mechanisms underlying these reactions have not been fully examined. We recently described the activation of circulating basophils by mosquito extracts in vitro in a patient with HMB. To further investigate this finding, we studied four additional patients with HMB. All patients showed typical clinical features of HMB after mosquito bites and they had NK lymphocytosis and high peripheral blood EBV DNA loads. We found evidence of EBV infection in NK cells through in situ hybridization that detected EBV‐encoded small RNA‐1, and flow cytometry showed HLA‐DR expression on almost all NK cells. Basophil activation tests with the extracts of epidemic mosquitoes Culex pipiens pallens and Aedes albopictus showed positive responses to one or both extracts in all samples from patients with HMB, suggesting the presence of mosquito antigen‐specific IgE and its binding to basophils. In particular, the extract of Aedes albopictus was able to activate basophils in all available patient samples. These results indicate that basophils and/or mast cells activated by mosquito bites may be involved in initiation and development of severe skin reactions to mosquito bites in HMB.
Cooperatively transcriptional and epigenetic regulation of sonic hedgehog overexpression drives malignant potential of breast cancer
Authors: Duan Zhao‐Heng , Wang Hao‐Chuan , Zhao Dong‐Mei , Ji Xiao‐Xin , Song Min , Yang Xiao‐Jun , Cui Wei
Published: May 2015

Sonic hedgehog (Shh), a ligand of Hedgehog signaling pathway, is considered an important oncogene and an exciting potential therapeutic target in several cancers. Comprehensive understanding of the regulation mechanism of Shh in cancer cells is necessary to find an effective approach to selectively block its tumorigenic function. We and others previously demonstrated that nuclear factor‐kappa B (NF‐κB) activation and promoter hypomethylation contributed to the overexpression of Shh. However, the relationship between transcriptional and epigenetic regulation of Shh, and their roles in the malignant phenotype of cancer cells are still not clearly elucidated. In the present study, our data showed that the level of Shh was higher in breast cancer tissues with positive NF‐κB nuclear staining and promoter hypomethylation. In addition, survival analysis revealed that Shh overexpression, but not hypomethylation and NF‐κB nuclear staining, was a poor prognosis indicator for breast cancers. Moreover, in vitro data demonstrated that both NF‐κB activation and hypomethylation in promoter region were positively associated with the overexpression of Shh. Mechanistically, the hypomethylation in Shh promoter could facilitate NF‐κB binding to its site, and subsequently cooperate to induce transcription of Shh. Furthermore, the biological function data indicated that overexpressed Shh enhanced the self‐renewal capacity and migration ability of breast cancer cells, which could be augmented by promoter demethylation and NF‐κB activation. Overall, our findings reveal multiple and cooperative mechanisms of Shh upregulation in cancer cells, and the roles of Shh in tumor malignant behavior, thus suggesting a new strategy for therapeutic interventions to reduce Shh in tumors and improve patients’ prognosis.
Associations between metabolomic‐identified changes of biomarkers and arterial stiffness in subjects progressing to impaired fasting glucose
Authors: Jung Saem , Kim Minjoo , Lee Young Ju , Lee Sang‐Hyun , Lee Jong Ho
Published: May 2015

Objective

We investigated correlations between age‐related changes in circulating metabolites and arterial stiffness in impaired fasting glucose (IFG).

Design, subjects, measurement

This prospective cohort study included 602 healthy, normal fasting glucose (NFG) subjects (30–65 years old) who underwent triennial medical evaluation. After 3 years, 9·3% of subjects developed IFG (n = 56). Age, gender, BMI and fasting glucose were used to match the remaining NFG subjects (n = 546) that were included for the control group (NFG group, n = 80).

Results

After 3 years, levels of fasting glucose, insulin and malondialdehyde, and brachial–ankle pulse wave velocity (baPWV) were significantly greater in the IFG group than in the NFG group after adjusting for baseline values. The IFG group had a greater increase in lactosylceramide (P = 0·001, q < 0·05) and a greater reduction in phosphatidylcholine (PC) (18:0/20:4) than the NFG group. Multiple linear regression analysis showed that the change in baPWV was independently and positively associated with changes in fasting glucose and lactosylceramide. In all subjects, lactosylceramide levels positively correlated with changes in baPWV and fasting glucose, while premenopausal women were not shown, and negatively correlated with changes in PC and LDL particle size.

Conclusions

This study indicates that age‐related increase in circulating lactosylceramide is an independent predictor of increased arterial stiffness in subjects with impaired fasting glucose.
Association between salivary amylase (AMY1) gene copy numbers and insulin resistance in asymptomatic Korean men
Authors: Choi Y.‐J. , Nam Y.‐S. , Yun J. M. , Park J. H. , Cho B. L. , Son H.‐Y. , Kim J. I. , Yun J. W.
Published: May 2015

Aims

Salivary amylase gene (AMY1) copy number variations (CNVs) correlate directly with salivary amylase activity and serum amylase levels. Previously, individuals with high AMY1 CNVs exhibited low postprandial glucose levels and postprandial early insulin surge, suggesting that high AMY1 gene copy numbers may play a role in lowering the risk of insulin resistance.

Methods

We verified the relationship between AMY1 CNVs and homeostatic model assessment–insulin resistance (HOMA‐IR) in a cohort of 1257 Korean men aged 20–65 years who visited two medical centres for regular health check‐ups, and in subgroups of current smokers and regular alcohol drinkers. Individuals with fasting plasma glucose levels > 10.0 mmol/l, HbA1c ≥ 64 mmol/mol (8.0%) or who used oral hypoglycaemic agents or insulin were excluded.

Results

AMY1 CNVs correlated negatively with HOMA‐IR even after adjusting for covariates (e.g. BMI, systolic blood pressure, triacylglycerol, alcohol consumption, smoking and physical activity). When the participants were divided according to current smoking and alcohol consumption habits, negative correlations between AMY1 CNVs and HOMA‐IR were more evident among non‐smokers and regular drinkers and were non‐significant among smokers and non‐regular drinkers.

Conclusions

Low AMY1 CNVs correlated with high insulin resistance in asymptomatic Korean men, and such a relationship presented differently according to the status of smoking and alcohol consumption.
Association of IRF8 gene polymorphisms with autoimmune thyroid disease
Authors: Lin Jiunn‐Diann , Wang Yuan‐Hung , Liu Chia‐Hung , Lin Ying‐Chin , Lin Jui‐An , Lin Yuh‐Feng , Tang Kam‐Tsun , Cheng Chao‐Wen
Published: May 2015

Background

The occurrence of autoimmune thyroid disease (AITD) is known to have a major adverse effect on interferon (INF)‐α treatment. The genetic variant of the INF regulatory factor 8 (IRF8), a type 1 INF regulator, is associated with susceptibility to systemic lupus erythematosus and multiple sclerosis. In this study, we investigated possible associations of the IRF8 polymorphisms, rs17445836 and rs2280381, with AITD in an ethnic Chinese population.

Material and methods

In total, 278 patients with Graves' disease (GD) and 55 patients with Hashimoto's thyroiditis (HT), and 252 healthy controls were enrolled. Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) and direct sequencing were used for genotyping.

Results

Significantly lower frequencies of the GA genotype and A allele of rs17445836 were found in the HT group than in the control group (P = 0·028, odds ratio (OR) = 4·71 and P = 0·022, OR = 4·40, respectively). Both rs17445836 and rs2280381 were associated with the presence of an antimicrosomal antibody (AmiA), and rs2280381 was also associated with the presence of an antithyroglobulin antibody (ATA) in AITD. Moreover, rs17445836 was associated with the level of AmiA in AITD.

Conclusions

rs17445836 of IRF8 is a possible genetic variant associated with the development of HT. rs17445836 was associated with the production of thyroid antibody, and the GG genotype of rs17445836 was associated with a higher AmiA titre than the GA genotype.
Why Do Fund Families Release Underperforming Incubated Mutual Funds?
Authors: Shirley Sara E. , Stark Jeffrey R.
Published: May 2015

Although the average incubated mutual fund outperforms nonincubated funds by up to 3.41% annually, a large number of released funds underperform during incubation. We find that launching underperforming incubated mutual funds is associated with objectives that attract large inflows and lower relative risk. These findings are consistent with the use of incubation to maximize fee revenue through means other than the flow‐to‐performance relationship. We also find that underperforming incubated funds are incubated longer suggesting that families release funds opportunistically to take advantage of outperformance when it is observed.
Hypofibrinogenemia and liver disease: a new case of Aguadilla fibrinogen and review of the literature
Authors: Casini A. , Sokollik C. , Lukowski S. W. , Lurz E. , Rieubland C. , de Moerloose P. , Neerman‐Arbez M.
Published: May 2015

Introduction

Fibrinogen storage disease (FSD) is characterized by hypofibrinogenemia and hepatic inclusions due to impaired release of mutant fibrinogen which accumulates and aggregates in the hepatocellular endoplasmic reticulum. Liver disease is variable.

Aim

We studied a new Swiss family with fibrinogen Aguadilla. In order to understand the molecular peculiarity of FSD mutations, fibrinogen Aguadilla and the three other causative mutations, all located in the γD domain, were modelled.

Method

The proband is a Swiss girl aged 4 investigated because of fatigue and elevated liver enzymes. Protein structure models were prepared using the Swiss‐PdbViewer and POV‐Ray software.

Results

The proband was found to be heterozygous for fibrinogen Aguadilla: FGG Arg375Trp. Familial screening revealed that her mother and maternal grandmother were also affected and, in addition, respectively heterozygous and homozygous for the hereditary haemochromatosis mutation HFE C282Y. Models of backbone and side‐chain interactions for fibrinogen Aguadilla in a 10‐angstrom region revealed the loss of five H‐bonds and the gain of one H‐bond between structurally important amino acids. The structure predicted for fibrinogen Angers showed a novel helical structure in place of hole ‘a’ on the outer edge of γD likely to have a negative impact on fibrinogen assembly and secretion.

Conclusion

The mechanism by which FSD mutations generate hepatic intracellular inclusions is still not clearly established although the promotion of aberrant intermolecular strand insertions is emerging as a likely cause. Reporting new cases is essential in the light of novel opportunities of treatment offered by increasing knowledge of the degradation pathway and autophagy.
Results of a phase I/II open‐label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients
Authors: Martinowitz U. , Lissitchkov T. , Lubetsky A. , Jotov G. , Barazani‐Brutman T. , Voigt C. , Jacobs I. , Wuerfel T. , Santagostino E.
Published: May 2015

Introduction

rIX‐FP is a coagulation factor IX (recombinant), albumin fusion protein with more than fivefold half‐life prolongation over other standard factor IX (FIX) products available on the market.

Aim

This prospective phase II, open‐label study evaluated the safety and efficacy of rIX‐FP for the prevention of bleeding episodes during weekly prophylaxis and assessed the haemostatic efficacy for on‐demand treatment of bleeding episodes in previously treated patients with haemophilia B.

Methods

The study consisted of a 10–14 day evaluation of rIX‐FP pharmacokinetics (PK), and an 11 month safety and efficacy evaluation period with subjects receiving weekly prophylaxis treatment. Safety was evaluated by the occurrence of related adverse events, and immunogenic events, including development of inhibitors. Efficacy was evaluated by annualized spontaneous bleeding rate (AsBR), and the number of injections to achieve haemostasis.

Results

Seventeen subjects participated in the study, 13 received weekly prophylaxis and 4 received episodic treatment only. No inhibitors were detected in any subject. The mean and median AsBR were 1.25, and 1.13 respectively in the weekly prophylaxis arm. All bleeding episodes were treated with 1 or 2 injections of rIX‐FP. Three prophylaxis subjects who were treated on demand prior to study entry had >85% reduction in AsBR compared to the bleeding rate prior to study entry.

Conclusion

This study demonstrated the efficacy for weekly routine prophylaxis of rIX‐FP to prevent spontaneous bleeding episodes and for the treatment of bleeding episodes. In addition no safety issues were detected during the study and an improved PK profile was demonstrated.