bluuebunny/crossref_metadata_2025 huggingface dataset:
Simplified mechanistic models of gene regulation for analysis and design
Authors: Hancock Edward J. , Stan Guy-Bart , Arpino James A. J. , Papachristodoulou Antonis
Published: June 2015

Simplified mechanistic models of gene regulation are fundamental to systems biology and essential for synthetic biology. However, conventional simplified models typically have outputs that are not directly measurable and are based on assumptions that do not often hold under experimental conditions. To resolve these issues, we propose a ‘model reduction’ methodology and simplified kinetic models of total mRNA and total protein concentration, which link measurements, models and biochemical mechanisms. The proposed approach is based on assumptions that hold generally and include typical cases in systems and synthetic biology where conventional models do not hold. We use novel assumptions regarding the ‘speed of reactions’, which are required for the methodology to be consistent with experimental data. We also apply the methodology to propose simplified models of gene regulation in the presence of multiple protein binding sites, providing both biological insights and an illustration of the generality of the methodology. Lastly, we show that modelling total protein concentration allows us to address key questions on gene regulation, such as efficiency, burden, competition and modularity.
Contaminant adhesion (aerial/ground biofouling) on the skin of a gecko
Authors: Watson Gregory S. , Cribb Bronwen W. , Schwarzkopf Lin , Watson Jolanta A.
Published: June 2015

In this study, we have investigated the micro- and nano-structuring and contaminant adhesional forces of the outer skin layer of the ground dwelling gecko—
Lucasium steindachneri.
The lizard's skin displayed a high density of hairs with lengths up to 4 μm which were spherically capped with a radius of curvature typically less than 30 nm. The adhesion of artificial hydrophilic (silica) and hydrophobic (C
18
) spherical particles and natural pollen grains were measured by atomic force microscopy and demonstrated extremely low values comparable to those recorded on superhydrophobic insects. The lizard scales which exhibited a three-tier hierarchical architecture demonstrated higher adhesion than the trough regions between scales. The two-tier roughness of the troughs comprising folding of the skin (wrinkling) limits the number of contacting hairs with particles of the dimensions used in our study. The gecko skin architecture on both the dorsal and trough regions demonstrates an optimized topography for minimizing solid–solid and solid–liquid particle contact area, as well as facilitating a variety of particulate removal mechanisms including water-assisted processes. These contrasting skin topographies may also be optimized for other functions such as increased structural integrity, levels of wear protection and flexibility of skin for movement and growth. While single hair adhesion is low, contributions of many thousands of individual hairs (especially on the abdominal scale surface and if deformation occurs) may potentially aid in providing additional adhesional capabilities (sticking ability) for some gecko species when interacting with environmental substrates such as rocks, foliage and even man-made structuring.
Bone strain magnitude is correlated with bone strain rate in tetrapods: implications for models of mechanotransduction
Authors: Aiello B. R. , Iriarte-Diaz J. , Blob R. W. , Butcher M. T. , Carrano M. T. , Espinoza N. R. , Main R. P. , Ross C. F.
Published: June 2015

Hypotheses suggest that structural integrity of vertebrate bones is maintained by controlling bone strain magnitude via adaptive modelling in response to mechanical stimuli. Increased tissue-level strain magnitude and rate have both been identified as potent stimuli leading to increased bone formation. Mechanotransduction models hypothesize that osteocytes sense bone deformation by detecting fluid flow-induced drag in the bone's lacunar–canalicular porosity. This model suggests that the osteocyte's intracellular response depends on fluid-flow rate, a product of bone strain rate and gradient, but does not provide a mechanism for detection of strain magnitude. Such a mechanism is necessary for bone modelling to adapt to loads, because strain magnitude is an important determinant of skeletal fracture. Using strain gauge data from the limb bones of amphibians, reptiles, birds and mammals, we identified strong correlations between strain rate and magnitude across clades employing diverse locomotor styles and degrees of rhythmicity. The breadth of our sample suggests that this pattern is likely to be a common feature of tetrapod bone loading. Moreover, finding that bone strain magnitude is encoded in strain rate at the tissue level is consistent with the hypothesis that it might be encoded in fluid-flow rate at the cellular level, facilitating bone adaptation via mechanotransduction.
Peto's paradox and the promise of comparative oncology
Authors: Nunney Leonard , Maley Carlo C. , Breen Matthew , Hochberg Michael E. , Schiffman Joshua D.
Published: June 2015

The past several decades have seen a paradigm shift with the integration of evolutionary thinking into studying cancer. The evolutionary lens is most commonly employed in understanding cancer emergence, tumour growth and metastasis, but there is an increasing realization that cancer defences both between tissues within the individual and between species have been influenced by natural selection. This special issue focuses on discoveries of these deeper evolutionary phenomena in the emerging area of ‘comparative oncology’. Comparing cancer dynamics in different tissues or species can lead to insights into how biology and ecology have led to differences in carcinogenesis, and the diversity, incidence and lethality of cancers. In this introduction to the special issue, we review the history of the field and outline how the contributions use empirical, comparative and theoretical approaches to address the processes and patterns associated with ‘Peto's paradox’, the lack of a statistical relationship of cancer incidence with body size and longevity. This burgeoning area of research can help us understand that cancer is not only a disease but is also a driving force in biological systems and species life histories. Comparative oncology will be key to understanding globally important health issues, including cancer epidemiology, prevention and improved therapies.
Cancer susceptibility and reproductive trade-offs: a model of the evolution of cancer defences
Authors: Boddy Amy M. , Kokko Hanna , Breden Felix , Wilkinson Gerald S. , Aktipis C. Athena
Published: June 2015

The factors influencing cancer susceptibility and why it varies across species are major open questions in the field of cancer biology. One underexplored source of variation in cancer susceptibility may arise from trade-offs between reproductive competitiveness (e.g. sexually selected traits, earlier reproduction and higher fertility) and cancer defence. We build a model that contrasts the probabilistic onset of cancer with other, extrinsic causes of mortality and use it to predict that intense reproductive competition will lower cancer defences and increase cancer incidence. We explore the trade-off between cancer defences and intraspecific competition across different extrinsic mortality conditions and different levels of trade-off intensity, and find the largest effect of competition on cancer in species where low extrinsic mortality combines with strong trade-offs. In such species, selection to delay cancer and selection to outcompete conspecifics are both strong, and the latter conflicts with the former. We discuss evidence for the assumed trade-off between reproductive competitiveness and cancer susceptibility. Sexually selected traits such as ornaments or large body size require high levels of cell proliferation and appear to be associated with greater cancer susceptibility. Similar associations exist for female traits such as continuous egg-laying in domestic hens and earlier reproductive maturity. Trade-offs between reproduction and cancer defences may be instantiated by a variety of mechanisms, including higher levels of growth factors and hormones, less efficient cell-cycle control and less DNA repair, or simply a larger number of cell divisions (relevant when reproductive success requires large body size or rapid reproductive cycles). These mechanisms can affect intra- and interspecific variation in cancer susceptibility arising from rapid cell proliferation during reproductive maturation, intrasexual competition and reproduction.
Inclusive fitness effects can select for cancer suppression into old age
Authors: Brown Joel S. , Aktipis C. Athena
Published: June 2015

Natural selection can favour health at youth or middle age (high reproductive value) over health at old age (low reproductive value). This means, all else being equal, selection for cancer suppression should dramatically drop after reproductive age. However, in species with significant parental investment, the capacity to enhance inclusive fitness may increase the reproductive value of older individuals or even those past reproductive age. Variation in parental investment levels could therefore contribute to variation in cancer susceptibility across species. In this article, we describe a simple model and framework for the evolution of cancer suppression with varying levels of parental investment and use this model to make testable predictions about variation in cancer suppression across species. This model can be extended to show that selection for cancer suppression is stronger in species with cooperative breeding systems and intergenerational transfers. We consider three cases that can select for cancer suppression into old age: (i) extended parental care that increases the survivorship of their offspring, (ii) grandparents contributing to higher fecundity of their children and (iii) cooperative breeding where helpers forgo reproduction or even survivorship to assist parents in having higher fecundity.
Cellular reprogramming dynamics follow a simple one-dimensional reaction coordinate
Authors: Pusuluri Sai Teja , Lang Alex H. , Mehta Pankaj , Castillo Horacio E.
Published: June 2015

Cellular reprogramming, the conversion of one cell type to another, has fundamentally transformed our conception of cell types. Cellular reprogramming induces global changes in gene expression involving hundreds of transcription factors and thousands of genes and understanding how cells globally alter their gene expression profile during reprogramming is an open problem. Here we reanalyze time-series data on cellular reprogramming from differentiated cell types to induced pluripotent stem cells (iPSCs) and show that gene expression dynamics during reprogramming follow a simple one-dimensional reaction coordinate. This reaction coordinate is independent of both the time it takes to reach the iPSC state as well as the details of experimental protocol used. Using Monte-Carlo simulations, we show that such a reaction coordinate emerges naturally from epigenetic landscape models of cell identity where cellular reprogramming is viewed as a “barrier-crossing” between the starting and ending cell fates. The model also provides gene-level insight into reprogramming dynamics and resolves a debate in the stem cell field about the different phases of reprogramming dynamics. Overall, our analysis and model suggest that gene expression dynamics during reprogramming follow a canonical trajectory consistent with the idea of an “ optimal path” in gene expression space for reprogramming.
Crystal structure of (E)-1,2-bis(4-bromo-2,6-difluorophenyl)diazene
Authors: Broichhagen Johannes , Woodmansee David H. , Trauner Dirk , Mayer Peter
Published: June 2015

In the crystal, molecules of the centrosymmetric title compound, C12H4Br2F4N2, are linked into strands along [011] by weak C—H...F contacts. Furthermore, the molecules are π–π stacked with perpendicular ring distances of 3.4530 (9) Å.
Examining the effectiveness of phishing filters against DNS based phishing attacks
Authors: Purkait Swapan
Published: June 2015

Purpose

– This paper aims to report on research that tests the effectiveness of anti-phishing tools in detecting phishing attacks by conducting some real-time experiments using freshly hosted phishing sites. Almost all modern-day Web browsers and antivirus programs provide security indicators to mitigate the widespread problem of phishing on the Internet.

Design/methodology/approach

– The current work examines and evaluates the effectiveness of five popular Web browsers, two third-party phishing toolbar add-ons and seven popular antivirus programs in terms of their capability to detect locally hosted spoofed websites. The same tools have also been tested against fresh phishing sites hosted on Internet.

Findings

– The experiments yielded alarming results. Although the success rate against live phishing sites was encouraging, only 3 of the 14 tools tested could successfully detect a single spoofed website hosted locally.

Originality/value

– This work proposes the inclusion of domain name system server authentication and verification of name servers for a visiting website for all future anti-phishing toolbars. It also proposes that a Web browser should maintain a white list of websites that engage in online monetary transactions so that when a user requires to access any of these, the default protocol should always be HTTPS (Hypertext Transfer Protocol Secure), without which a Web browser should prevent the page from loading.
Determinants of school efficiency
Authors: Huguenin Jean-Marc
Published: June 2015

Purpose

– The purpose of this paper is: to measure school technical efficiency and to identify the determinants of primary school performance.

Design/methodology/approach

– A two-stage data envelopment analysis (DEA) of school efficiency is conducted. At the first stage, DEA is employed to calculate an individual efficiency score for each school. At the second stage, efficiency is regressed on school characteristics and environmental variables.

Findings

– The mean technical efficiency of schools in the State of Geneva is equal to 93 per cent. By improving the operation of schools, 7 per cent (100−93) of inputs could be saved, representing 17,744,656 Swiss francs in 2010. School efficiency is negatively influenced by: operations being held on multiple sites, the proportion of disadvantaged pupils enroled at the school and the provision of special education, but positively influenced by school size (captured by the number of pupils).

Practical implications

– Technically, the determinants of school efficiency are outside of the control of headteachers. However, it is still possible to either boost the positive impact or curb the negative impact. In the context of the State of Geneva, the policy-related implications of the current study could be summarized as follows. New schools or existing multi-site schools should be concentrated on common sites; if this is not possible, the use of information and communication technology in school management and teaching should be developed and encouraged. In order to correct the negative influence of disadvantaged pupils on school performance, policymakers should focus on related social policies, such as pre-school, health, housing and benefits policies, rather than on allocating additional resources to schools. Finally, with an average of 381 pupils per school, school size could be increased to maximize school efficiency.

Originality/value

– Unlike most similar studies, the model in this study is tested for multicollinearity, heteroskedasticity and endogeneity. It is therefore robust. Moreover, one explanatory variable of school efficiency (operations being held on multiple sites) is a truly original variable as it has never been tested so far.
Co-design visual merchandising in 3D virtual stores: a facet theory approach
Authors: Wu Juanjuan , Kim Angella , Koo Jayoung
Published: June 2015

Purpose

– The purpose of this paper is to discover user-generated visual merchandising (VM) directives that could guide VM in physical stores as well as shed light on future development of customizable virtual stores for online retailing.

Design/methodology/approach

– Applying a facet theory approach, our research involved consumers (n=145) in co-designing VM directives in a 3D virtual store in collaboration with target corporation. In total, 67 virtual shops in three product categories, i.e., women’s ready-to-wear, boy’s Cherokee, and men’s swim wear, were content analysed, along with written reports.

Findings

– The research findings focused on the three facets of VM: merchandising presentation (fixturing, product density, manner of presentation, and product adjacency), in-store environment (layout and interior), and in-store promotion (signage). The research revealed the elements that these facets contain and the relationships between the elements. The findings suggest that retailers should design an ecological instead of a merely utilitarian environment; clear section identity helps shoppers find a sense of ownership and boundaries; and stores should also present a lifestyle solution instead of a merchandise selection.

Originality/value

– The research contributes both original creations of VM directives and a methodical framework that moves the subject of VM from the physical to the virtual environment and shifts the traditional in-house function of VM to an open innovation in which consumers participate.
Industrial branding in the digital age
Authors: Lipiäinen Heini Sisko Maarit , Karjaluoto Heikki
Published: June 2015

Purpose

– The purpose of this paper is to describe the overall branding logic of an international industrial company operating in the renewable energy industry and to respond to calls for empirical research on how to build a business-to-business (B2B) brand in the digital age and how digital media can be used for branding. A digital branding model is also developed.

Design/methodology/approach

– A single case study of a company at the forefront of digital media usage is used to develop the model. The main data come from semi-structured theme interviews and from content analysis of the channels used to create a brand on the Internet.

Findings

– In the digital age, firms seem to benefit from having a strong market orientation and a holistic branding approach with robust integration of their different functions. Branding in the digital age not only requires strong internal communication and consistent external communication, but also positioning of the brand in topical conversations. For an industrial organization, becoming an opinion leader is a strategy well-suited to branding and can be supported by creating relevant content subsequently delivered through various social media channels.

Research limitations/implications

– The results of this study are based on a single case study and hence are not generalizable.

Originality/value

– This study is among the first to respond to the calls for empirical research on industrial brand management in the digital age and contributes to the emerging B2B branding and branding on digital age literature.
Antecedents of social media B2B use in industrial marketing context: customers’ view
Authors: Keinänen Hanna , Kuivalainen Olli
Published: June 2015

Purpose

– The purpose of this study is to clarify business-to-business (B2B) customers’ behavior regarding their social media use for B2B purposes and the antecedents of this behavior in the industrial marketing setting. It explores the influence of corporate culture, colleagues’ support and personal and psychological factors on customer behavior toward social media business use.

Design/methodology/approach

– The authors conducted an online questionnaire survey among key customer accounts of an information technology service company (N = 82). Partial least squares (PLS) path modeling was utilized to analyze the relationship between the dependent variable (social media business use) and the independent variables.

Findings

– Results show that private social media usage has the most significant relationship with the social media business use. Colleagues at work are also supporting B2B social media use and personal characteristics are also of importance. Surprisingly, perception of usability of social media for B2B use did not explain social media business use within our sample.

Research limitations/implications

– The chosen methodology, sampling frame and sample size may limit generalizability. Therefore, researchers are encouraged to test the proposed hypothesis in other settings, particularly as the diffusion of B2B social media increases.

Practical implications

– The paper provides insights into how marketing managers can make an impact with their social media marketing. For example, when planning social media activities, companies need to consider which social media services could serve their marketing and communication targets and would reach the customers.

Originality/value

– Studies related to social media in B2B, especially from a customer’s perspective, are still limited, and the authors do not know how customer firms value industrial marketing activities in social media. This novel paper provides insights into managers’ reasons for using social media and gives guidelines for B2B marketers on how to conduct social media marketing in the future.
Big is beautiful: the information content of bank rating changes
Authors: Fieberg Christian , Körner Finn Marten , Prokop Jörg , Varmaz Armin
Published: June 2015

Purpose

– The purpose of this paper is to study the information content of about 3,300 global bank rating changes before and after the Lehman bankruptcy in September 2008 to assess if differences in stock market reactions for small and big banks emerge.

Design/methodology/approach

– The analysis of the stock market reactions of rating changes (upgrades and downgrades) and bank’s size (small and big) is conducted by an event study approach.

Findings

– The authors find that while upgrades are not associated with significant abnormal bank stock returns, downgrades have a significantly negative effect. This result holds for both small and big banks, while negative abnormal returns are considerably stronger for the former. For small banks, the authors observe an increase in negative cumulative abnormal returns post-Lehman. The lack of a reaction to large banks’ rating downgrades in the narrow [−1,+1] event window indicates that their stock prices may, to some extent, be insulated from negative rating information even post-Lehman, which the authors attribute to an implicit “too big to fail” subsidy anticipated by equity investors.

Originality/value

– This paper provides insights to the differences in the information content of changes in small and big banks’ credit rating on stock returns that is unrelated to the well-known size effect. Compared to small banks, big banks seem to some extent be insulated from negative rating changes even post-Lehman – contributing to the on-going too big to fail debate.
Effect of pomegranate seed powder, grape seed extract and tomato powder on the quality characteristics of chicken nuggets
Authors: Kaur Simranjeet , Kumar Sunil , Bhat Z. F. , Kumar Arvind
Published: June 2015

Purpose

– The purpose of this paper was to evaluate the effect of pomegranate seed powder, grape seed extract and tomato powder on the quality characteristics of chicken nuggets during refrigerated storage.

Design/methodology/approach

– The study was designed to evaluate the effect of pomegranate seed powder, grape seed extract and tomato powder on the storage quality parameters of chicken nuggets. The products were developed by incorporating optimum level of pomegranate seed powder (3 per cent), grape seed extract (0.3 per cent) and tomato powder (2 per cent) separately and were aerobically packaged in low-density polyethylene pouches and assessed for various storage quality parameters under refrigerated (4±1°C) conditions for 21 days of storage. The products were evaluated for various physico-chemical, microbiological and sensory parameters at regular intervals of 0, 7, 14 and 21 days.

Findings

– A significant (p
<
0.05) effect of pomegranate seed powder, grape seed extract and tomato powder was observed on the pH and thiobarbituric acid reacting substances (mg malondialdehyde/kg) values of the chicken nuggets. A significant (p
<
0.05) effect was also observed on the microbiological characteristics, as the products incorporated with pomegranate seed powder, grape seed extract and tomato powder showed significantly (p
<
0.05) lower values for total plate count, psychrophilic count and yeast and mould count during the period of storage. Coliforms were not detected throughout the period of storage. Significantly (p
<
0.05) higher scores were observed for various sensory parameters of the products incorporated with pomegranate seed powder (3 per cent), grape seed extract (0.3 per cent) and tomato powder (2 per cent).

Originality/value

– Pomegranate seed powder (3 per cent), grape seed extract (0.3 per cent) and tomato powder (2 per cent) successfully improved the oxidative stability and storage quality of the products during refrigerated (4±1°C) storage and may be commercially exploited to improve the storage quality of muscle foods without adversely affecting the sensory quality of the products.
Red meat consumption and type 2 diabetes mellitus risk
Authors: Derbyshire Emma , Ruxton Carrie
Published: June 2015

Purpose

– This review aims to evaluate and review literature published in the area of rising concerns that red meat consumption may be associated with risk of type 2 diabetes mellitus (T2DM), although there have been discrepancies between study findings, and put the findings into context.

Design/methodology/approach

– Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was undertaken to locate and summarise relevant studies which included epidemiological and clinical studies published between 2004 and 2014.

Findings

– A total of 23 studies were found, with 21 epidemiological and two clinical studies meeting the criteria. Overall, the totality of the evidence indicates that while processed meat consumption appears to be associated with T2DM risk, the effect is much weaker for red meat, with some associations attenuated after controlling for body weight parameters. Where studies have considered high intakes in relation to T2DM risk, meat intake has tended to exceed 600 g per week. Therefore, keeping red meat intakes within recommended guidelines of no more than 500 g per week, while opting for lean cuts or trimming fat, would seem to be an evidence-based response.

Research limitations/implications

– The majority of studies conducted to date have been observational cohorts which cannot determine cause and effect. Most of these used food frequency questionnaires which are known to be subject to misclassification errors (Brown, 2006). Clearly, more randomised controlled trials are needed to establish whether red meat consumption impacts on markers of glucose control. Until then, conclusions can only be viewed as speculative.

Originality/value

– This paper provides an up-to-date systematic review of the literature, looking at inter-relationships between red meat consumption and T2DM risk.
Integration of stakeholder interests in housing companies’ strategic management
Authors: Heitel Stephanie , Kämpf-Dern Annette , Pfnür Andreas
Published: June 2015

Purpose

– In addition to financial returns, German housing companies are expected to achieve social and ecological outcomes. This achievement is challenging for management, as expectations from different stakeholders are only partly apparent and often conflicting. The paper aims to discuss these issues.

Design/methodology/approach

– This paper presents a process model that supports the management of housing companies to systematically explore, evaluate, and integrate stakeholders’ interests into the company’s strategic targets.

Findings

– The integrated process model improves sustainable value creation, as stakeholders’ interests are transparent and can thus be better satisfied.

Research limitations/implications

– Due to the action research design, further research cycles and empirical testing with other companies are needed before findings can be generalised.

Practical implications

– The process enables housing companies to focus on value-generating activities, to react timely to changing needs, and to improve their relationships with stakeholders. Management benefits from increased clarity and legitimacy for strategic decisions as stakeholder demands are made transparent and integrated into the strategic targets.

Originality/value

– Compared to common participation approaches, all stakeholder groups are consulted, and their expectations are documented transparently within the suggested process model. This results in a better foundation for sustainable management planning and decisions.
Terminal osseous dysplasia with pigmentary defects; Case and brief review of filamin A‐related disorders
Authors: Bhabha Friyana K , Walsh Maie , Orchard David , Savarirayan Ravi
Published: June 2015

Terminal osseous dysplasia with pigmentary defects (TOD) is an extremely rare X‐linked dominant disorder, which is characterised by cutaneous digital fibromas, pigmentary skin defects and skeletal abnormalities. A single mutation in the last nucleotide of exon 31 of the filamin A gene (FLNA) has recently been identified as a cause of the disease. We describe a case of an 18‐month‐old girl with the clinical phenotype of TOD and the disease‐specific FLNA mutation confirmed by genetic testing. This report highlights the importance of recognising this distinct phenotype that can present to a wide variety of health‐care professionals, and reviews the spectrum of filamin A disorders.
How do you think she feels? Vulnerability in empathy and the role of attention in school‐aged children born extremely preterm
Authors: Campbell Catherine , Horlin Chiara , Reid Corinne , McMichael Judy , Forrest Laura , Brydges Chris , French Noel , Anderson Mike
Published: June 2015

The aim of this study was to examine empathic competence in children born extremely preterm (EP, <28 weeks) given vulnerabilities in social relationships. Empathy in typically developing children is mediated by executive functions. Executive functioning is also impaired in preterm children. Of particular interest in this study are the attentional components of executive functioning as mediators of empathic development. Thirty‐two 7‐year‐old EP children and 40 age‐matched term children participated in the Project K.I.D.S program and completed the Kids Empathy Development Scale (KEDS), Wechsler Intelligence Scale for Children (WISC‐IV), and Test of Everyday Attention for Children (TEA‐Ch). Children born extremely preterm exhibited poorer performance on all measures. The mediating role of attention in empathy competence was not supported by mediation modelling when FSIQ was controlled. As predicted, the EP group showed weaker empathic development relative to typically developing children. They also showed poorer attentional abilities. However, the effect of preterm birth on empathy was not mediated by executive‐level attention. The cognitive mechanisms underpinning poor empathy competence in EP children remain unclear. Future research needs to examine the role of inhibition, social–emotional recognition, and regulation.
Silent cerebral infarcts in very young children with sickle cell anaemia are associated with a higher risk of stroke
Authors: Cancio Maria I. , Helton Kathleen J. , Schreiber Jane E. , Smeltzer Matthew P. , Kang Guolian , Wang Winfred C.
Published: June 2015

Silent cerebral infarctions (SCI) are the most common neurological injury in children with sickle cell anaemia (SCA), but their incidence/prognosis in early childhood has not been well described. We report clinical, neuroradiological, psychometric and academic follow‐up over an average period of 14 years in 37 children with SCA who had magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the brain between ages 7 and 48 months. Ten patients (27%) younger than age 5 years (Group I) had SCI, as did 12 (32%) older than 5 years (Group II). Fifteen (41%) had no lesions (Group III). Overt stroke or transient ischaemic attack occurred in 5/9 (56%) in Group I. Most Group I patients had progressive MRI abnormalities, concurrent stenosis, decreased cognitive ability, attention/executive function deficits and hindered academic attainment. The proportions of subjects in Group I with subsequent neurological events (P ≤ 0·006), progressive ischaemia (P ≤ 0·001) and vascular stenosis (P ≤ 0·006) were greater than in Groups II and III. Thus, SCI in young children with SCA may predict overt central nervous system events, progressive MRI abnormalities, stenosis, cognitive dysfunction and poor academic performance. Children younger than 5 years may benefit from MRI/MRA testing and should be considered for aggressive intervention when SCI are detected.
Transmembrane Helix Assembly by Max–Min Ant System Algorithm
Authors: Sujaree Kanon , Kitjaruwankul Sunan , Boonamnaj Panisak , Supunyabut Chirayut , Sompornpisut Pornthep
Published: June 2015

Because of the rapid progress in biochemical and structural studies of membrane proteins, considerable attention has been given on developing efficient computational methods for solving low‐to‐medium resolution structures using sparse structural data. In this study, we demonstrate a novel algorithm, max–min ant system (MMAS), designed to find an assembly of α‐helical transmembrane proteins using a rigid helix arrangement guided by distance constraints. The new algorithm generates a large variety with finite number of orientations of transmembrane helix bundle and finds the solution that is matched with the provided distance constraints based on the behavior of ants to search for the shortest possible path between their nest and the food source. To demonstrate the efficiency of the novel search algorithm, MMAS is applied to determine the transmembrane packing of KcsA and MscL ion channels from a limited distance information extracted from the crystal structures, and the packing of KvAP voltage sensor domain using a set of 10 experimentally determined constraints, and the results are compared with those of two popular used stochastic methods, simulated annealing Monte Carlo method and genetic algorithm.
Synthesis, Biological Evaluation, and Docking of Dihydropyrazole Sulfonamide Containing 2‐hydroxyphenyl Moiety: A Series of Novel MMP‐2 Inhibitors
Authors: Wang Peng‐Fei , Qiu Han‐Yue , Baloch Shahla Karim , Gong Hai‐Bin , Wang Zhong‐Chang , Zhu Hai‐Liang
Published: June 2015

In this study, we synthesized a series of dihydropyrazole sulfonamide derivatives containing 2‐hydroxyphenyl moiety as antitumor agents to target the matrix metalloproteinase‐2 (MMP‐2). All of the synthesized compounds were examined by bioactivity assays, in which compound 4c turned out as a potential antagonist of MMP‐2 along with potent anticancer activity against four tumor cell lines. Structure–activity relationship analysis was also performed to examine how structural changes impacted the bioactivity. Suggested to be caused by the induction of apoptosis, the antitumor mechanism of 4c was further confirmed by PI combining with annexin V‐FITC staining assay using flow cytometry analysis. These new findings along with molecular docking observations suggested that compound 4c could be developed as a potential anticancer agent.
Dentists’ self‐estimation of their competence to treat avulsion and root fracture injuries
Authors: Skaare Anne B , Pawlowski Andrzej Adam , Maseng Aas Anne‐Lise , Espelid Ivar
Published: June 2015

Aim

The purpose of this study was to evaluate the knowledge of Norwegian dentists on avulsion and root fracture injuries.

Method

An electronic questionnaire (QuestBack) was sent in 2012 to all dentists (n = 255) employed in the Public Dental Service (PDS) in three counties of Norway. The dentists were asked to state whether they felt they had sufficient competence to treat avulsion and root fractures immediately and long term. Based on international guidelines, the authors achieved a consensus for ideal treatment. Based on two cases, the clinicians were to assess their own competence. They were classified into either a ‘sufficient competence’ (SC) group or an ‘insufficient competence’ (ISC) group. The data were evaluated by descriptive statistics and chi‐square bivariate analysis.

Results

The response rate was 64%, 95 dentists (62%) in the SC group and 58 (38%) in the ISC group. Significantly more young dentists responded (P < 0.001). Correct treatment (reposition and splint) for a one‐day‐old fracture in the middle third of the root with luxation of the coronal fragment was chosen more often by the SC group compared with the ISC group (P = 0.03), but estimating the long‐term prognosis, there was no difference (P = 0.14). In a case with a previous avulsion injury and obvious signs of pulp necrosis and external infection‐related root resorption, the majority (n = 97, 63%) would choose root canal treatment with a Ca(OH)₂ dressing which was considered correct treatment, but fewer than half of the clinicians (40%) diagnosed the external infection related to root resorption which was visible on a radiograph. There was no difference between the groups (P = 0.81).

Conclusion

The study shows that overall knowledge among Norwegian dentists is good, but more knowledge on detecting and diagnosing external root resorption is needed. Self‐estimation of own competence does not reflect level of knowledge.
Transient visual responses reset the phase of low‐frequency oscillations in the skeletomotor periphery
Authors: Wood Daniel K. , Gu Chao , Corneil Brian D. , Gribble Paul L. , Goodale Melvyn A.
Published: June 2015

We recorded muscle activity from an upper limb muscle while human subjects reached towards peripheral targets. We tested the hypothesis that the transient visual response sweeps not only through the central nervous system, but also through the peripheral nervous system. Like the transient visual response in the central nervous system, stimulus‐locked muscle responses (< 100 ms) were sensitive to stimulus contrast, and were temporally and spatially dissociable from voluntary orienting activity. Also, the arrival of visual responses reduced the variability of muscle activity by resetting the phase of ongoing low‐frequency oscillations. This latter finding critically extends the emerging evidence that the feedforward visual sweep reduces neural variability via phase resetting. We conclude that, when sensory information is relevant to a particular effector, detailed information about the sensorimotor transformation, even from the earliest stages, is found in the peripheral nervous system.
Formation of a hard tissue barrier after experimental pulp capping or partial pulpotomy in humans: an updated systematic review
Authors: Fransson H. , Wolf E. , Petersson K.
Published: June 2015

The aim was to update a systematic review of pulp capping and partial pulpotomy by Olsson et al. (2006), by evaluating new evidence on formation of a hard tissue barrier after pulp capping and partial pulpotomy of experimental exposures in humans. PubMed (01‐01‐2005 to 01‐03‐2014) and CENTRAL were searched using specific keywords. Hand searches were made and the level of evidence for each included article was evaluated by the authors. The evidence of the conclusions was graded as strong, moderately strong, limited or insufficient. The initial search in PubMed yielded 215 abstracts. Hand searches of reference lists yielded no additional original scientific articles. After a selection process and interpretation, 22 articles were included and rated for level of evidence: no article was rated as high and seven as moderate. Overall the methodological quality of studies has improved since the previous systematic review was published in 2006. The conclusions are that there is limited scientific evidence that application of calcium hydroxide or mineral trioxide aggregate to an exposed pulp frequently results in formation of a hard tissue barrier, whereas adhesives or enamel matrix derivatives do not. There is insufficient scientific evidence that mineral trioxide aggregate promotes hard tissue formation more frequently than calcium hydroxide.
Mast cell–macrophage dynamics in modulation of dengue virus infection in skin
Authors: Chu Ya‐Ting , Wan Shu‐Wen , Anderson Robert , Lin Yee‐Shin
Published: June 2015

Dengue virus (DENV) infection causes dengue fever, dengue haemorrhagic fever, or dengue shock syndrome. Mast cells have been speculated to play a role in DENV disease although their precise roles are unclear. In this study, we used mast cell‐deficient KitW‐sh/W‐sh mice to investigate the involvement of mast cells after intradermal DENV infection. An approximately two‐ to three‐fold higher level of DENV NS3 antigen was detected at the skin inoculation site in DENV‐infected KitW‐sh/W‐sh mice than in DENV‐infected wild‐type (WT) mice (using a dose of 1 × 109 plaque‐forming units/mouse). Moreover, as an indicator of heightened pathogenesis, a more prolonged bleeding time was observed in DENV‐infected KitW‐sh/W‐sh mice than in WT mice. Monocytes/macrophages are considered to be important targets for DENV infection, so we investigated the susceptibility and chemokine response of DENV‐infected peritoneal macrophages from KitW‐sh/W‐sh and WT mice both ex vivo and in vivo. There was a tendency for higher DENV infection and higher secretion of CCL2 (MCP‐1) from peritoneal macrophages isolated from KitW‐sh/W‐sh mice than those from WT mice. In vivo studies using intradermal inoculation of DENV showed about twofold higher levels of infiltrating macrophages and CCL2 (MCP‐1) at the inoculation site in both mock control and DENV‐inoculated KitW‐sh/W‐sh mice than in corresponding WT mice. In summary, compared with WT mice, KitW‐sh/W‐sh mice show enhanced DENV infection and macrophage infiltration at the skin inoculation site as well as increased DENV‐associated bleeding time. The results indicate an intriguing interplay between mast cells and tissue macrophages to restrict DENV replication in the skin.
rIL‐10 enhances IL‐10 signalling proteins in foetal alveolar type II cells exposed to hyperoxia
Authors: Lee Hyeon‐Soo , Lee Dong Gun
Published: June 2015

Although the mechanisms by which hyperoxia promotes bronchopulmonary dysplasia are not fully defined, the inability to maintain optimal interleukin (IL)‐10 levels in response to injury secondary to hyperoxia seems to play an important role. We previously defined that hyperoxia decreased IL‐10 production and pre‐treatment with recombinant IL‐10 (rIL‐10) protected these cells from injury. The objectives of these studies were to investigate the responses of IL‐10 receptors (IL‐10Rs) and IL‐10 signalling proteins (IL‐10SPs) in hyperoxic foetal alveolar type II cells (FATIICs) with and without rIL‐10. FATIICs were isolated on embryonic day 19 and exposed to 65%‐oxygen for 24 hrs. Cells in room air were used as controls. IL‐10Rs protein and mRNA were analysed by ELISA and qRT‐PCR, respectively. IL‐10SPs were assessed by Western blot using phospho‐specific antibodies. IL‐10Rs protein and mRNA increased significantly in FATIICs during hyperoxia, but JAK1 and TYK2 phosphorylation showed the opposite pattern. To evaluate the impact of IL‐8 (shown previously to be increased) and the role of IL‐10Rs, IL‐10SPs were reanalysed in IL‐8‐added normoxic cells and in the IL‐10Rs’ siRNA‐treated hyperoxic cells. The IL‐10Rs’ siRNA‐treated hyperoxic cells and IL‐8‐added normoxic cells showed the same pattern in IL10SPs with the hyproxic cells. And pre‐treatment with rIL‐10 prior to hyperoxia exposure increased phosphorylated IL‐10SPs, compared to the rIL‐10‐untreated hyperoxic cells. These studies suggest that JAK1 and TYK2 were significantly suppressed during hyperoxia, where IL‐8 may play a role, and rIL‐10 may have an effect on reverting the suppressed JAK1 and TYK2 in FATIICs exposed to hyperoxia.
Association between overweight/obesity and increased risk of periodontitis
Authors: Suvan Jean E. , Petrie Aviva , Nibali Luigi , Darbar Ulpee , Rakmanee Thanasak , Donos Nikos , D'Aiuto Francesco
Published: June 2015

Objective

To investigate periodontitis as a co‐morbidity of overweight/obesity in an age‐matched sample of periodontitis cases or periodontally healthy controls.

Methods

Participants were periodontally assessed using whole mouth clinical periodontal measures. Multivariable conditional logistic regression was used to calculate the odds ratio for diagnosis of periodontitis when body mass index (kg/m2), overweight (BMI 25–29.99 kg/m2, or obese BMI ≥ 30 kg/m2) were the explanatory variables. A receiver operating characteristic (ROC) curve was generated of all possible BMI (kg/m2) cut‐off points discriminating individuals for diagnosis of periodontitis.

Results

The study comprised 286 participants. BMI showed a dose–response association with increased odds (1.12 per increase of 1 kg/m2, 95% CI 1.05–1.20, p = 0.001) of being a case compared to a control independent of gender, ethnicity, smoking status and dental plaque level. Similarly overweight/obese were independently associated with increased odds of diagnosis of periodontitis for overweight (OR = 2.56, 95% CI 1.210–5.400, p = 0.014) and for obese (OR = 3.11, 95% CI 1.052–6.481, p = 0.015) compared to normal weight individuals. The ROC curve analysis confirmed diagnosis of periodontitis was 1.6 times more likely in an individual with the BMI ≥ 24.32 kg/m2.

Conclusions

Overweight/obese individuals are more likely to suffer from periodontitis compared to normal weight individuals in this case–control sample.
Comparing clinical and economic outcomes of biologic and conventional medications in postmenopausal women with osteoporosis
Authors: Hernandez Inmaculada , Zhang Yuting
Published: June 2015

Rationale, aims and objectives

Biologics are substantially more expensive than their conventional counterparts but it is unclear whether extra costs deliver better health outcomes. We compare clinical and economic outcomes between teriparatide (monthly costs $1120) and bisphosphonates (monthly costs $14) among postmenopausal women with osteoporosis.

Methods

From a 5% random sample of Medicare beneficiaries, we selected women newly diagnosed with osteoporosis between 1 January 2007 and 31 December 2011 and who initiated teriparatide or bisphosphonates after the diagnosis. We followed them up until one of these events: switching osteoporosis treatment, death, or the end of study period ‐ 31 December 2011. Clinical outcomes included hip fracture, vertebral fracture, fracture of radius, ulna or carpal bones, other upper limb fractures, other lower limb fractures and any fracture. Economic outcomes included medical costs, pharmacy costs, and total costs associated with osteoporosis. Using conventional propensity score, high‐dimensional propensity score and instrumental variable analysis, we constructed Cox proportional hazards models to evaluate the risk of fracture and two‐part models to compare costs.

Results

Teriparatide users had higher risk of fracture and higher costs, compared with similar bisphosphonates users. The hazard ratios of fracture for teriparatide relative to bisphosphonates ranged from 1.37 to 2.12, depending on methods. There was no difference in the risk of hip fracture between treatment groups. Total annual costs related to osteoporosis were between $2733 and $3352 higher for teriparatide users.

Conclusions

The biological agent, teriparatide, is more expensive yet less effective than conventional treatment, bisphosphonates.