bluuebunny/crossref_metadata_2025 huggingface dataset:
Testase 1 (ADAM 24) a sperm surface metalloprotease is required for normal fertility in mice
Authors: Zhu Guo‐Zhang , Gupta Surabhi , Myles Diana Gold , Primakoff Paul
Published: September 2009

ADAM family members play important roles in various physiological and pathological processes, for example, fertilization, embryogenesis, neurogenesis, and development of asthma and arthritis (Primakoff and Myles, 2000. Trends Genet 16: 83–87; Edwards et al., 2008. Mol Aspects Med 29: 258–289). We previously reported that testase 1 (ADAM 24) is the first identified metalloprotease present on the surface of mature sperm. To investigate a potential role of testase 1 in fertilization, we generated testase 1 deficient mice. Testase 1 null male mice showed reduced fertility, producing only half the number of offspring when compared to wild‐type littermates. In a standard in vitro fertilization assay, we found that sperm lacking testase 1 gave rise to polyspermic fertilization, a phenotypic feature that might contribute to failure of normal embryo development due to polyaneuploidy. Furthermore, in vivo, we found that testase 1 null males produced a higher number of polyspermic embryos at the pronuclear stage. These findings suggest that testase 1 is a sperm plasma membrane component which contributes to the prevention of polyspermy at the level of the oocyte plasma membrane. Mol. Reprod. Dev. 76: 1106–1114, 2009. © 2009 Wiley‐Liss, Inc.
Evoked myotonia can be “dialed‐up” by increasing stimulus train length in myotonic dystrophy type 1
Authors: Logigian Eric L. , Twydell Paul , Dilek Nuran , Martens William B. , Quinn Chris , Wiegner Allen W. , Heatwole Chad R. , Thornton Charles A. , Moxley Richard T.
Published: September 2009

It is unknown how evoked myotonia varies with stimulus frequency or train length, or how it compares to voluntary myotonia in myotonic dystrophy type 1 (DM1). First dorsal interosseous (FDI) tetanic contractions evoked by trains of 10–20 ulnar nerve stimuli at 10–50 HZ were recorded in 10 DM1 patients and 10 normals. For comparison, maximum voluntary handgrip contractions were also recorded. An automated computer program placed cursors along the declining (relaxation) phase of the force recordings at 90% and 5% of peak force (PF) and calculated relaxation times (RTs) between these points. For all stimulus frequencies and train lengths, evoked RTs were much shorter, and evoked PFs were much greater in normals than in DM1. In normals, evoked RT was independent of stimulus frequency and train length, while in DM1 RT was longer for train lengths of 20 stimuli (mean: 9 s in DM1; 0.20 in normals) than for 10 stimuli (mean: 3 s in DM1, 0.19 in normals), but it did not change with stimulus frequency. In both groups PF increased greatly as stimulus frequency rose from 10–50 HZ but only slightly as train length rose from 10–20 stimuli. Voluntary handgrip RT (mean: 1.9 s) was less than evoked FDI RT (mean: 9 s). In DM1, evoked RT can be “dialed up” by increasing stimulus train length. Evoked myotonia testing utilizing a stimulus paradigm of at least 20 stimuli at 30–50 HZ may be useful in antimyotonic drug trials, particularly when grip RT is normal or equivocal. Muscle Nerve, 2010
Rheological characteristics of solid–fluid transition in dry granular dense flows: A thermodynamically consistent constitutive model with a pressure‐ratio order parameter
Authors: Fang Chung
Published: September 2009

Dry granular flows are characterized as quasi‐static, dense and collisional states by the interactions among the grains, which is indexed macroscopically by an internal variable, called the order parameter defined as the square root of the static pressure to the total pressure. The solid–fluid state transition is regarded as a second‐order phase transition process, and is described by a kinematic evolution of the order parameter. The thermodynamic analysis, based on the Müller–Liu entropy principle, is employed to deduce the equilibrium responses of the constitutive equations, while the dynamic responses are postulated on the basis of a quasi‐linear and the second‐order Ginzburg–Landau phase transition theories. The obtained model is applied to study the rheological characteristics of a dry granular dense flow between two infinite parallel plates, of which the results are compared with those from DEM simulations to estimate the model validity. The present study provides a general framework for the theoretical justifications on the thermodynamic consistencies of order‐parameter‐based constitutive models, and can be extended to flows in quasi‐static or collisional states. Copyright © 2009 John Wiley & Sons, Ltd.
Steady‐state solution for cylindrical penetrometers
Authors: Klar Assaf , Pinkert Shmulik
Published: September 2009

This paper suggests a new method for obtaining steady‐state solutions for ‘full‐flow’ penetrometers. The method is based on the numerical solution of the small strain plastic‐flow problem (i.e. rigid plastic material) with an inhomogeneous strength field, which is determined by converting changes of material properties over time in a stationary frame of reference into spatial distribution of strength in a moving frame of reference. Rather than building streamlines from back integration of soil element distortion, as previous methods have suggested, the method treats the domain as continuous with the associated field equations. The method employs an upstream weighting technique for the determination of information flow within the domain. The execution order for the calculation is based on topological ordering. This results in the calculation having a complexity of O(N), as compared with O(N1.5) for the strain path or streamline methods (N is the number of discretized points), which significantly reduces the calculation time. The formulation is presented for the cylindrical (T‐bar) penetrometer, and includes aspects of soil strength degradation, strain rate effects, strength anisotropy, and interface strength law. Comparison to previously published values, based on large displacement finite element simulations with remeshing, showed good agreement, indicating on the correctness of the suggested approach. Investigation into the soil rigid‐body rotation and the remolding effect on anisotropy characteristics showed an interesting behavior, where the decrease of strength anisotropy due to remolding has a greater influence when the soil strength is higher in the vertical direction. Copyright © 2009 John Wiley & Sons, Ltd.
An adaptive stabilization strategy for enhanced strain methods in non‐linear elasticity
Authors: Ten Eyck Alex , Lew Adrian
Published: September 2009

This paper proposes and analyzes an adaptive stabilization strategy for enhanced strain (ES) methods applied to quasistatic non‐linear elasticity problems. The approach is formulated for any type of enhancements or material models, and it is distinguished by the fact that the stabilization term is solution dependent. The stabilization strategy is first constructed for general linearized elasticity problems, and then extended to the non‐linear elastic regime via an incremental variational principle. A heuristic choice of the stabilization parameters is proposed, which in the numerical examples proved to provide stable approximations for a large range of deformations, different problems and material models. We also provide explicit lower bounds for the stabilization parameters that guarantee that the method will be stable. These are not advocated, since they are generally larger than the ones based on heuristics, and hence prone to deteriorate the locking‐free behavior of ES methods. Numerical examples with two different non‐linear elastic models in thin geometries and incompressible situations show that the method remains stable and locking free over a large range of deformations. Finally, the method is strongly based on earlier developments for discontinuous Galerkin methods, and hence throughout the paper we offer a perspective about the similarities between the two. Copyright © 2009 John Wiley & Sons, Ltd.
Error estimation in a stochastic finite element method in electrokinetics
Authors: Clénet S. , Ida N.
Published: September 2009

Input data to a numerical model are not necessarily well known. Uncertainties may exist both in material properties and in the geometry of the device. They can be due, for instance, to ageing or imperfections in the manufacturing process. Input data can be modelled as random variables leading to a stochastic model. In electromagnetism, this leads to solution of a stochastic partial differential equation system. The solution can be approximated by a linear combination of basis functions rising from the tensorial product of the basis functions used to discretize the space (nodal shape function for example) and basis functions used to discretize the random dimension (a polynomial chaos expansion for example). Some methods (SSFEM, collocation) have been proposed in the literature to calculate such approximation. The issue is then how to compare the different approaches in an objective way. One solution is to use an appropriate a posteriori numerical error estimator. In this paper, we present an error estimator based on the constitutive relation error in electrokinetics, which allows the calculation of the distance between an average solution and the unknown exact solution. The method of calculation of the error is detailed in this paper from two solutions that satisfy the two equilibrium equations. In an example, we compare two different approximations (Legendre and Hermite polynomial chaos expansions) for the random dimension using the proposed error estimator. In addition, we show how to choose the appropriate order for the polynomial chaos expansion for the proposed error estimator. Copyright © 2009 John Wiley & Sons, Ltd.
MALDI‐TOF MS‐based drug susceptibility testing of pathogens: The example of Candida albicans and fluconazole
Authors: Marinach Carine , Alanio Alexandre , Palous Martine , Kwasek Stéphanie , Fekkar Arnaud , Brossas Jean‐Yves , Brun Sophie , Snounou Georges , Hennequin Christophe , Sanglard Dominique , Datry Annick , Golmard Jean‐Louis , Mazier Dominique
Published: September 2009

MALDI‐TOF MS can be used for the identification of microorganism species. We have extended its application to a novel assay of Candida albicans susceptibility to fluconazole, based on monitoring modifications of the proteome of yeast cells grown in the presence of varying drug concentrations. The method was accurate, and reliable, and showed full agreement with the Clinical Laboratory Standards Institute's reference method. This proof‐of‐concept demonstration highlights the potential for this approach to test other pathogens.
Mechanism of formation of the C‐terminal β‐hairpin of the B3 domain of the immunoglobulin binding protein G from Streptococcus. III. Dynamics of long‐range hydrophobic interactions
Authors: Lewandowska Agnieszka , Ołdziej Stanisław , Liwo Adam , Scheraga Harold A.
Published: September 2009

A 20‐residue peptide, IG(42–61), derived from the C‐terminal β‐hairpin of the B3 domain of the immunoglobulin binding protein G from Streptoccocus was studied using circular dichroism, nuclear magnetic resonance (NMR) spectroscopy at various temperatures and by differential scanning calorimetry (DSC). Unlike other related peptides studied so far, this peptide displays two heat capacity peaks in DSC measurements (at a scanning rate of 1.5 deg/min at a peptide concentration of 0.07 mM), which suggests a three‐state folding/unfolding process. The results from DSC and NMR measurements suggest the formation of a dynamic network of hydrophobic interactions stabilizing the structure, which resembles a β‐hairpin shape over a wide range of temperatures (283–313 K). Our results show that IG (42–61) possesses a well‐organized three‐dimensional structure stabilized by long‐range hydrophobic interactions (Tyr50 ··· Phe57 and Trp48 ··· Val59) at T = 283 K and (Trp48 ··· Val59) at 305 and 313 K. The mechanism of β‐hairpin folding and unfolding, as well as the influence of peptide length on its conformational properties, are also discussed. Proteins 2010. © 2009 Wiley‐Liss, Inc.
Backbone dynamics of TFE‐induced native‐like fold of region 4 of Escherichia coli RNA polymerase σ70 subunit
Authors: Kaczka Piotr , Polkowska‐Nowakowska Agnieszka , Bolewska Krystyna , Zhukov Igor , Poznański Jarosław , Wierzchowski Kazimierz L.
Published: September 2009

Folding of a recombinant protein rECσ comprising domain 4 of E. coli RNA polymerase σ70 subunit, upon addition of 2,2,2‐trifluoroethanol (TFE) to its aqueous solution, was monitored by heteronuclear NMR spectroscopy. The TFE‐induced migration of resonance signals in a series of 15N‐HSQC spectra displayed sequence‐dependent heterogeneity. A common trend of uniform upfield shift in both 1H and 15N dimensions, indicative of generation of helical structures, breaks down for some residues almost cooperatively at 10–15% TFE (v/v), pointing to the buildup of non‐helical regions separating the initially induced helices. The preferences of residues to assume either helical or non‐helical conformation are correlated with the location in the sequence rather than with their type. CSI descriptors and 15N relaxation data obtained for the protein at 10% TFE allowed characterization of the stability of the pre‐folded state of rECσ. By all the criteria applied, three highly populated α‐helical regions separated by much more flexible residues forming a loop and a turn in the DNA‐binding HLHTH motif were identified. The location of the secondary structure elements along the protein sequence coincides with those found in homologous proteins, and with the helix nucleation regions determined in unfolded rECσ at low pH. The bimodal distribution of the 15N relaxation parameters enabled identification of residues forming a framework of the folded protein strictly corresponding to the HLHTH motif, bracketed by unfolded terminal regions. Thus, in respect to rECσ in aqueous solution TFE acts not only as a strong helix inducer, but also as a folding agent. Proteins 2010. © 2009 Wiley‐Liss, Inc.
Slow formation of aggregation‐resistant β‐sheet folding intermediates
Authors: Junker Mirco , Clark Patricia L.
Published: September 2009

Protein folding has been studied extensively for decades, yet our ability to predict how proteins reach their native state from a mechanistic perspective is still rudimentary at best, limiting our understanding of folding‐related processes in vivo and our ability to manipulate proteins in vitro. Here, we investigate the in vitro refolding mechanism of a large β‐helix protein, pertactin, which has an extended, elongated shape. At 55 kDa, this single domain, all‐β‐sheet protein allows detailed analysis of the formation of β‐sheet structure in larger proteins. Using a combination of fluorescence and far‐UV circular dichroism spectroscopy, we show that the pertactin β‐helix refolds remarkably slowly, with multiexponential kinetics. Surprisingly, despite the slow refolding rates, large size, and β‐sheet‐rich topology, pertactin refolding is reversible and not complicated by off‐pathway aggregation. The slow pertactin refolding rate is not limited by proline isomerization, and 30% of secondary structure formation occurs within the rate‐limiting step. Furthermore, site‐specific labeling experiments indicate that the β‐helix refolds in a multistep but concerted process involving the entire protein, rather than via initial formation of the stable core substructure observed in equilibrium titrations. Hence pertactin provides a valuable system for studying the refolding properties of larger, β‐sheet‐rich proteins, and raises intriguing questions regarding the prevention of aggregation during the prolonged population of partially folded, β‐sheet‐rich refolding intermediates. Proteins 2010. © 2009 Wiley‐Liss, Inc.
Fipronil resistance in the whitebacked planthopper (Sogatella furcifera): possible resistance mechanisms and cross‐resistance
Authors: Tang Jian , Li Jian , Shao Ying , Yang Baojun , Liu Zewen
Published: September 2009

BACKGROUND: The whitebacked planthopper (WBPH), Sogatella furcifera (Horváth), is a major rice pest in many parts of Asia. Fipronil has been widely used to control rice pests, and resistance to fipronil has been reported in some important species.

RESULTS: A field population (F) of WBPH was collected, with 50.5‐fold resistance to fipronil, which increased to 137.5‐fold (F‐se) after continuous selection for 11 generations. The F‐se population did not show significant cross‐resistance to the insecticides examined by comparison with the F population. TPP (synergism ratio 1.9), DEM (1.5) and PBO (1.1) showed only slight synergism on fipronil in the F‐se population. A large increase was found in esterase and P450 monooxygenase activity in the F‐se population. In vitro, PBO inhibited both esterase and P450 monooxygenase activity, and TPP inhibited esterase activity in the F‐se population.

CONCLUSION: Synergistic study in vivo and biochemical study in vitro indicated that esterase and P450 monooxygenases might be important factors for fipronil resistance in the selected population F‐se. However, these biochemical factors could not lead to such high resistance (137.5‐fold) in the F‐se population, and target‐site insensitivity would be another or more important factor. Copyright © 2009 Society of Chemical Industry
Quality specifications for peptide drugs: a regulatory‐pharmaceutical approach
Authors: Vergote Valentijn , Burvenich Christian , Van de Wiele Christophe , De Spiegeleer Bart
Published: September 2009

Peptide drugs, as all types of pharmaceuticals, require adequate specifications (i.e. quality attributes, procedures and acceptance criteria) as part of their quality assurance to ensure the safety and efficacy of drug substances (i.e. active pharmaceutical ingredients) and drug products (i.e. finished pharmaceutical dosage forms). Compendial monographs are updated regularly to keep up with the most recent advances in peptide synthesis (e.g. reduced by‐products) and analytical technology. Nevertheless, currently applied pharmacopoeial peptide specifications are barely harmonized yet (e.g. large differences between the European Pharmacopoeia and the United States Pharmacopeia), increasing the manufacturers' burden of performing analytical procedures in different ways, using different acceptance criteria. Additionally, the peptide monographs are not always consistent within a single pharmacopoeia. In this review, we highlight the main differences and similarities in compendial peptide specifications (including identification, purity and assay). Based on comparison, and together with additional information from peptide drug substance manufacturers and public evaluation reports on registration files of non‐pharmacopoeial peptide drugs, a consistent monograph structure is proposed. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.
Reinforcement learning design for cancer clinical trials
Authors: Zhao Yufan , Kosorok Michael R. , Zeng Donglin
Published: September 2009

We develop reinforcement learning trials for discovering individualized treatment regimens for life‐threatening diseases such as cancer. A temporal‐difference learning method called Q‐learning is utilized that involves learning an optimal policy from a single training set of finite longitudinal patient trajectories. Approximating the Q‐function with time‐indexed parameters can be achieved by using support vector regression or extremely randomized trees. Within this framework, we demonstrate that the procedure can extract optimal strategies directly from clinical data without relying on the identification of any accurate mathematical models, unlike approaches based on adaptive design. We show that reinforcement learning has tremendous potential in clinical research because it can select actions that improve outcomes by taking into account delayed effects even when the relationship between actions and outcomes is not fully known. To support our claims, the methodology's practical utility is illustrated in a simulation analysis. In the immediate future, we will apply this general strategy to studying and identifying new treatments for advanced metastatic stage IIIB/IV non‐small cell lung cancer, which usually includes multiple lines of chemotherapy treatment. Moreover, there is significant potential of the proposed methodology for developing personalized treatment strategies in other cancers, in cystic fibrosis, and in other life‐threatening diseases. Copyright © 2009 John Wiley & Sons, Ltd.
Nonviral in Situ Green Fluorescent Protein Labeling and Culture of Primary, Adult Human Hair Follicle Epithelial Progenitor Cells
Authors: Tiede Stephan , Koop Norbert , Kloepper Jennifer E. , Fässler Reinhard , Paus Ralf
Published: September 2009

In this article we show that cloning of the human K15 promoter before a green fluorescence protein (GFP)/geneticin-resistance cassette and transfection of microdissected, organ-cultured adult human scalp hair follicles generates specific K15 promoter–driven GFP expression in their stem cell–rich bulge region. K15-GFP+ cells can be visualized in situ by GFP fluorescence and 2-photon laser scanning microscopy. Vital K15-GFP+ progenitor cells can then be selected by using the criteria of their green fluorescence, adhesion to collagen type IV and fibronectin, and geneticin resistance. Propagated K15-GFP+ cells express epithelial progenitor markers, show the expected differential gene expression profile of human bulge epithelium, and form holoclones. This application of nonretroviral, K15 promoter–driven, GFP labeling to adult human hair follicles facilitates the characterization and manipulation of human epithelial stem cells, both in situ and in vitro, and should be transferable to other complex human tissues.

Disclosure of potential conflicts of interest is found at the end of this article.
Multipathway Kinase Signatures of Multipotent Stromal Cells Are Predictive for Osteogenic Differentiation
Authors: Platt Manu O. , Wilder Catera L. , Wells Alan , Griffith Linda G. , Lauffenburger Douglas A.
Published: September 2009

Bone marrow-derived multipotent stromal cells (MSCs) offer great promise for regenerating tissue. Although certain transcription factors have been identified in association with tendency toward particular MSC differentiation phenotypes, the regulatory network of key receptor-mediated signaling pathways activated by extracellular ligands that induce various differentiation responses remains poorly understood. Attempts to predict differentiation fate tendencies from individual pathways in isolation are problematic due to the complex pathway interactions inherent in signaling networks. Accordingly, we have undertaken a multivariate systems approach integrating experimental measurement of multiple kinase pathway activities and osteogenic differentiation in MSCs, together with computational analysis to elucidate quantitative combinations of kinase signals predictive of cell behavior across diverse contexts. In particular, for culture on polymeric biomaterial surfaces presenting tethered epidermal growth factor, type I collagen, neither, or both, we have found that a partial least-squares regression model yields successful prediction of phenotypic behavior on the basis of two principal components comprising the weighted sums of eight intracellular phosphoproteins: phospho-epidermal growth factor receptor, phospho-Akt, phospho-extracellular signal-related kinase 1/2, phospho-heat shock protein 27, phospho-c-Jun, phospho-glycogen synthase kinase 3α/β, phospho-p38, and phospho-signal transducer and activator of transcription 3. This combination provides the strongest predictive capability for 21-day differentiated phenotype status when calculated from day-7 signal measurements; day-4 and day-14 signal measurements are also significantly predictive, indicating a broad time frame during MSC osteogenesis wherein multiple pathways and states of the kinase signaling network are quantitatively integrated to regulate gene expression, cell processes, and ultimately, cell fate.

Disclosure of potential conflicts of interest is found at the end of this article.
A Novel Role for γ-Secretase in the Formation of Primitive Streak-like Intermediates from ES Cells in Culture
Authors: Hughes James N. , Dodge Natasha , Rathjen Peter D. , Rathjen Joy
Published: September 2009

γ-Secretase is a membrane-associated protease with multiple intracellular targets, a number of which have been shown to influence embryonic development and embryonic stem (ES) cell differentiation. This paper describes the use of the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) to evaluate the role of γ-secretase in the differentiation of pluripotent stem cells to the germ lineages. The addition of DAPT did not prevent the formation of primitive ectoderm-like cells from ES cells in culture. In contrast, the addition of DAPT during primitive ectoderm-like cell differentiation interfered with the ability of both serum and BMP4 to induce a primitive streak-like intermediate and resulted in the preferential formation of neurectoderm. Similarly, DAPT reduced the formation of primitive streak-like intermediates from differentiating human ES cells; the culture conditions used resulted in a population enriched in human surface ectoderm. These data suggest that γ-secretase may form part of the general pathway by which mesoderm is specified within the primitive streak. The addition of an E-cadherin neutralizing antibody was able to partially reverse the effect of DAPT, suggesting that DAPT may be preventing the formation of primitive streak-like intermediates and promoting neurectoderm differentiation by stabilizing E-cadherin and preventing its proteolysis.

Disclosure of potential conflicts of interest is found at the end of this article.
MPR1 as a novel selection marker in Saccharomyces cerevisiae
Authors: Ogawa‐Mitsuhashi Kaoru , Sagane Koji , Kuromitsu Junro , Takagi Hiroshi , Tsukahara Kappei
Published: September 2009

L‐Azetidine‐2‐carboxylic acid (AZC) is a toxic four‐membered ring analogue of L‐proline that is transported into cells by proline transporters. AZC and L‐proline in the cells are competitively incorporated into nascent proteins. When AZC is present in a minimum medium, misfolded proteins are synthesized in the cells, thereby inhibiting cell growth. The MPR1 gene has been isolated from the budding yeast Saccharomyces cerevisiae Σ1278b as a multicopy suppressor of AZC‐induced growth inhibition. MPR1 encodes a novel acetyltransferase that detoxifies AZC via N‐acetylation. Since MPR1 is absent in the laboratory strain of S. cerevisiae S288C, it could be a positive selection marker that confers AZC resistance in the S288C background strains. To examine the usefulness of MPR1, we constructed some plasmid vectors that harboured MPR1 under the control of various promoters and introduced them into the S288C‐derived strains. The expression of MPR1 conferred AZC resistance that was largely dependent on the expression level of MPR1. In an additional experiment, the galactose‐inducible MPR1 and ppr1+, the fission yeast Schizosaccharomyces pombe homologue of MPR1, were used for gene disruption by homologous recombination, and here AZC‐resistant colonies were also successfully selected. We concluded that our MPR1–AZC system provides a powerful tool for yeast transformation. Copyright © 2009 John Wiley & Sons, Ltd.
The ‘Broken Society’ Election: Class Hatred and the Politics of Poverty and Place in Glasgow East
Authors: Mooney Gerry
Published: September 2009

This paper considers some of the ways in which representations of people experiencing poverty and disadvantaged places continue to be informed by ideas of individual inadequacy, dependency and disorder. Drawing on media reportage of poverty during the Glasgow East by-election in July 2008, it argues not only that people defined as ‘poor’ and locales that are severely disadvantaged continue to be ‘othered’ through such narratives, but also that this provides a clear indication of the ways in which the politics of poverty and state welfare are increasingly being fought-out in the media. It is argued that such misrecognition amounts to social injustice and stands in the way of progressive approaches to poverty and social welfare.
Defining the Issue: The Intersection of Domestic Abuse and Disability
Authors: Nixon Jennifer
Published: September 2009

This paper reports the findings of a qualitative study on the politicisation of domestic violence as it relates to the experiences of disabled survivors and argues that definitions of domestic violence are currently being debated within the disability and domestic violence spheres. Data are drawn from interviews with participants who have been active in politicising this issue and are affiliated to either the disabled people's movement or the movement against domestic violence in England and North Carolina. Although this issue is becoming increasingly politicised, this paper argues the process is currently marked by widespread discrepancies in defining domestic violence experienced by disabled people.
Understanding the exercise of agency within structural inequality: the case of personal debt
Authors: Orton Michael
Published: September 2009

This article contributes to debates about agency (meaning the behaviour of individuals) and structure, by drawing on empirical research into personal debt. Consideration of debt allows for debate about agency and structure beyond the narrow confines of welfare, and for the examination of agency in relation to citizens at different points in the broader socio-economic structure, not solely poor people. Based on the research findings, themselves grounded in interviewees' experience, the question of why two people in the same material circumstances will have different experiences becomes reframed as why two people whose exercise of agency is the same, face very different outcomes? It is argued that while the research supports a ‘both-and’ rather than ‘either-or’ approach to understanding agency and structure, a ‘both-and’ approach still does not fully capture the experience of interviewees. The key point is that the exercise of agency is overlaid onto structural inequality, and it is understanding the exercise of ‘agency within structure’ that is critical.
‘It Didn't Always Work’: Low-Income Children's Experiences of Changes in Mothers’ Working Patterns in the UK
Authors: Ridge Tess
Published: September 2009

Underpinning Labour's welfare-to-work policies is an assumption that employment will benefit disadvantaged children and their families. However, the effect of low-income and unstable employment on lone mothers and their children is uncertain. This article draws on interviews with children drawn from a qualitative, longitudinal study of low-income working family life, to explore the accounts of those children whose mother's entry into the labour market was unsuccessful. The article examines how children experienced their mother's employment and the impact of ‘failed’ work transitions on their well-being and their perceptions of the value of work for them and their families.
Indonesian Children's Views and Experiences of Work and Poverty
Authors: Bessell Sharon
Published: September 2009

While the causes of child labour are multifaceted and complex, economic disadvantage is generally identified as an important contributing factor. Child labour is also cited as perpetuating poverty. The precise relationship between child labour and poverty is, however, contested. This paper aims to deepen understanding of the relationship between children's work and poverty by focusing on children's views and experiences. Drawing on research with children in Indonesia, this paper examines two questions. First, how do working children define and experience poverty? Second, how do working children view the relationship between their work and poverty?
Effect of bone chip orientation on quantitative estimates of changes in bone mass using digital subtraction radiography
Authors: Mol André , Dunn Stanley M.
Published: September 2009

Objectives:  To assess the effect of the orientation of arbitrarily shaped bone chips on the correlation between radiographic estimates of bone loss and true mineral loss using digital subtraction radiography.

Methods:  Twenty arbitrarily shaped bone chips (dry weight 1–10 mg) were placed individually on the superior lingual aspect of the interdental alveolar bone of a dry dentate hemi‐mandible. After acquiring the first baseline image, each chip was rotated 90 degrees and a second radiograph was captured. Follow‐up images were created without the bone chips and after rotating the mandible 0, 1, 2, 4, and 6 degrees around a vertical axis. Aluminum step tablet intensities were used to normalize image intensities for each image pair. Follow‐up images were registered and geometrically standardized using projective standardization. Bone chips were dry ashed and analyzed for calcium content using atomic absorption.

Results:  No significant difference was found between the radiographic estimates of bone loss from the different bone chip orientations (Wilcoxon: P > 0.05). The correlation between the two series of estimates for all rotations was 0.93 (Spearman: P < 0.05). Linear regression analysis indicated that both correlates did not differ appreciably (

and

).

Conclusion:  It is concluded that the spatial orientation of arbitrarily shaped bone chips does not have a significant impact on quantitative estimates of changes in bone mass in digital subtraction radiography. These results were obtained in the presence of irreversible projection errors of up to six degrees and after application of projective standardization for image reconstruction and image registration.
Root surface debridement and endotoxin removal
Authors: Cadosch J. , Zimmermann U. , Ruppert M. , Guindy J. , Case D. , Zappa U.
Published: September 2009

Objective:  This study assessed associations between the number of standardized scaling strokes and the reduction of endotoxin on the root surface.

Background:  Therapy of periodontally involved teeth attempts removal of accretions by scaling and root planing. The amount of mechanical therapy required to free the root surface from etiologic factors remains unknown.

Methods:  Twenty‐four extracted human caries‐free single rooted teeth with at least 5 mm attachment loss were used. A region of interest (ROI) which contained subgingival calculus was defined on the root surface of each tooth. Standardized force instrumentation was applied using a force‐measuring curet. Fifty working strokes were applied to every ROI. Forces applied were recorded. The force recordings were converted from Millivolts into Newtons (N). After every unit of 5 strokes, presence of calculus was evaluated and scaling debris was collected. Endotoxin concentration was determined in the debris samples.

Results:  The endotoxin values for strokes 1–5 were statistically significantly greater than the values from all other stroke intervals. Complete calculus removal occured after a mean of 9.3 strokes. The endotoxin concentration reached a minimal level with concentrations of 0.03–0.306 EU/ml after calculus removal was complete.

Conclusion:  These findings suggest that completion of calculus removal coincides with endotoxin levels associated with clinically healthy teeth.
Effect of soluble receptors to interleukin‐1 and tumor necrosis factor alpha on experimentally induced root resorption in rats
Authors: Zhang Dongliang , Goetz Werner , Braumann Bert , Bourauel Christoph , Jaeger Andreas
Published: September 2009

Objective:  In this study, the role of the inflammatory cytokines interleukin‐1 (IL‐1) and tumor necrosis factor alpha (TNFα) in the course of mechanically induced root resorption was investigated.

Methods:  Mechanical induction of root resorption was performed on the upper left first molars in 18 male Wistar rats according to the method of Nakane and Kameyama. Starting on day minus 1, six animals received daily intraperitoneal injections of 2 ml of 1 µg/ml soluble receptors to IL‐1 (sIL‐1RII) and another six animals were administered the same dose of soluble receptors to TNFα (sTNFα‐RI). Six animals served as a control. On d 7 the left maxillae were prepared for histological and morphometric analysis of the extent of the root resorption that had developed.

Results:  The qualitative and quantitative results demonstrated that in both receptor groups the amount of root resorption was significantly reduced. Especially following systemic application of sTNFα‐RI, root resorption was nearly completely prevented.

Conclusions:  Our results indicate that IL‐1 and more particularly TNFα are important for the induction and the further process of mechanically induced root resorption in the rat.
Unique genes induced by mechanical stress in periodontal ligament cells
Authors: Myokai Fumio , Oyama Masataka , Nishimura Fusanori , Ohira Taisuke , Yamamoto Tadashi , Arai Hideo , Takashiba Shogo , Murayama Yoji
Published: September 2009

Objectives:  The aim of this study is to isolate mechanical stress‐induced genes (MSGens) from human periodontal ligament (PDL) cells and to analyze profiles of the mRNA expression of these genes.

Background:  Differential expression of genes in PDL cells under physiological stress such as occlusal force is thought to be orchestrated not only for the remodeling of PDL itself but also for the repair and regeneration of periodontal tissues. However, little is known about the genes expressed in PDL cells under mechanical stress.

Methods:  The cDNA from mechanical stress‐applied human PDL cells was subtracted against the cDNA from static control cells. The subtracted cDNA was amplified by polymerase chain reaction (PCR) and cloned for further analysis.

Results:  Among 68 independent clones isolated, 15 contained DNA fragments greater than 250 bp. Reverse Northern analysis revealed a marked induction of MSGen‐15 and MSGen‐28 mRNA expression in the mechanical stress‐applied cells. However, little difference in the magnitude of expression for the other MSGens was detected between the stress‐applied cells and the control cells. After nucleotide sequencing and the analysis of homology with known genes, five clones were identified; ribosomal protein S27 (MSGen‐9), MRG 15 (MSGen‐15), androgen‐binding protein (MSGen‐18), cathepsin H (MSGen‐28), and cytochrome c (MSGen‐47). Interestingly, it has been reported that MRG 15 is a novel transcription factor involved in the regulation of cell growth and senescence. The remaining 10 clones, classified into six sequence types, had no significant homology with any known genes.

Conclusions:  These results suggest that many known and unknown genes are expressed in response to mechanical stress in PDL cells, and that a transcription factor, MRG 15, may be responsible for molecular events in PDL cells under mechanical stress.
Effect of Emdogain® on human periodontal fibroblasts in an in vitro wound‐healing model
Authors: Rincon J. C. , Haase H. R. , Bartold P. M.
Published: September 2009

Objective:  The aim of this study was to evaluate the influence of Emdogain® (EMD) on cultured gingival fibroblasts, periodontal ligament fibroblasts and dermal fibroblasts, using an in vitro model of wound healing.

Background:  Enamel matrix derivative has been demonstrated to promote periodontal regeneration. However, the precise mechanisms by which this agent acts are still unclear.

Methods:  The effect of EMD on proliferation of the cells was studied using subconfluent cultures of gingival fibroblasts and periodontal ligament fibroblasts. The cells were made quiescent overnight and then stimulated with various concentrations of EMD (10, 50, 100 and 150 μg/ml) for 24 h. Negative and positive controls were cells cultured in media containing 0.2% and 10% fetal calf serum (FCS). The DNA synthesis was measured by the cellular uptake of [3H]thymidine. For in vitro wounding the cells were cultured, wounded and stimulated with 0.2% FCS, 10% FCS and EMD at a concentration of 20 μg/ml. The percentage of wound fill after treatment was measured after d 1, 4, 6, 12 and 16. The proliferation of cells was also calculated by the extent of incorporation of crystal violet.

Results:  The results demonstrated that cells in vitro fill an empty space by a combination of proliferation and cell migration. The most rapid closure of a wound area occurred where both proliferation and migration can occur as was seen when wounded cultures were maintained in 10% FCS or at a concentration of 20 μg/ml EMD which promoted proliferation.

Conclusions:  Therefore, EMD appears to exert an influence on cells that is compatible with improved wound healing.
The herpesvirus–Porphyromonas gingivalis–periodontitis axis
Authors: Slots J. , Kamma J.J. , Sugar C.
Published: September 2009

Objectives and background:  Members of the herpesvirus family have accumulated considerable support for a role in severe types of periodontitis. This study aimed to examine whether human cytomegalovirus (HCMV), Epstein–Barr virus type 1 (EBV‐1) or herpes simplex virus (HSV) together with the major periodontopathic bacterium Porphyromonas gingivalis might interact in the pathogenesis of periodontal breakdown.

Methods:  Sixteen subjects each contributed paper point samples from two progressing and two stable periodontitis lesions, as determined by ongoing loss of probing attachment. Polymerase chain reaction methodology was used to identify subgingival herpesviruses, P. gingivalis and other bacterial pathogens. Chi‐squared tests and multivariate logistic regression were employed to identify statistical associations between herpesviruses, periodontopathic bacteria and clinical variables.

Results:  HCMV and HSV were both significant predictors of the presence of subgingival P. gingivalis. In turn, P. gingivalis was positively associated with periodontitis active disease, probing attachment level, probing pocket depth, gingival bleeding upon probing and patient age. EBV‐1 was not linked to P. gingivalis, although the virus was predictive of periodontitis active disease. The periodontitis disease risk associated with herpesvirus–P. gingivalis combinations depended on both site‐specific and subject‐specific factors.

Conclusion:  The present data of aggressive periodontitis implicate HCMV, HSV and P. gingivalis as either cofactors in its etiology or triggers of relapses. Further studies are needed to determine the spectrum of periodontopathogenicity of herpesviruses and effective management of these viruses in periodontal sites.
The effects of enamel matrix derivative (EMD) on osteoblastic cells in culture and bone regeneration in a rat skull defect
Authors: Yoneda Satoshi , Itoh Daisuke , Kuroda Shinji , Kondo Hisatomo , Umezawa Akihiro , Ohya Keiichi , Ohyama Takashi , Kasugai Shohei
Published: September 2009

Objective:  Enamel matrix derivative (EMD) has been clinically used to promote periodontal tissue regeneration. The purpose of the present study is to clarify EMD affects on osteoblastic cells and bone regeneration.

Materials and Methods:  Mouse osteoblastic cells (ST2 cells and KUSA/A1 cells) are used in culture experiments. After cells were treated with EMD, cell growth was evaluated with DNA measurement, 5‐bromo‐2′‐deoxyurydine (BrdU) incorporation assay. Measurement of alkaline phosphatase (ALP) activity and mineralized‐nodule (MN) formation, Northern blotting analysis and zymography are also performed. In addition, EMD was applied to a rat skull defect and the defect was radiographically and histologically evaluated 2 weeks after the application.

Results:  EMD did not stimulate ST2 cell growth; however, it enhanced KUSA/A1 cell proliferation. Although EMD stimulated ALP activity in both the cells, ALP activity in KUSA/A1 cells was affected to a much greater degree. Corresponding to the increase in ALP activity, MN formation in KUSA/A1 cells was enhanced by EMD. EMD stimulated osteoblastic phenotype expression of KUSA/A1 cells such as type I collagen, osteopontin, transforming growth factor beta 1 and osteocalcin. EMD treatment also stimulated matrix metalloproteinase production in KUSA/A1 cells. Although the effects of EMD on osteoblastic cells depend on cell type, the overall effect of EMD on osteoblastic cells is stimulatory rather than inhibitory. Finally, EMD application to a rat skull defect accelerated new bone formation.

Conclusion:  These results indicate that EMD affects osteoblastic cells and has potential as a therapeutic material for bone healing.
Povidone‐iodine as a periodontal pocket disinfectant
Authors: Hoang T. , Jorgensen M. G. , Keim R. G. , Pattison A. M. , Slots J.
Published: September 2009

Objectives and background: Povidone‐iodine [polyvinylpyrrolidone‐iodine complex (PVP‐iodine)] might constitute a valuable adjunct to current periodontal therapy because of its broad‐spectrum antimicrobial activity, low potential for developing resistance and adverse reactions, wide availability, ease of use, and low financial cost. This investigation employed a randomized, split‐mouth study design to determine the microbiological and clinical effects of 10% PVP‐iodine subgingival irrigation in periodontitis lesions showing radiographic evidence of subgingival calculus.

Methods: Sixteen adults having at least one periodontal pocket of 6 mm or more in each quadrant of the dentition and harboring one or more periodontopathic bacteria participated in the study. In each subject, a study site in each quadrant was randomly chosen to receive either subgingival irrigation with 10% PVP‐iodine together with scaling and root planing, scaling and root planing alone, subgingival irrigation with 10% PVP‐iodine, or subgingival irrigation with sterile saline. Prior to therapy and at 5 weeks post‐treatment, microbiological culture was carried out without knowledge of the clinical status or the type of treatment rendered. A blinded clinical examiner determined presence of dental plaque, probing pocket depth, and gingival bleeding on probing. Microbiological and clinical data were analyzed using a repeated measures analysis of variance and Kruskal–Wallis rank test with the Tukey and Mann–Whitney post hoc tests.

Results: At 5 weeks post‐treatment, subgingival irrigation with PVP‐iodine together with scaling and root planing caused a 95% or greater reduction in total pathogen counts in 44% of pockets having ≥ 6 mm depth whereas scaling and root planing alone, povidone‐iodine irrigation alone and water irrigation alone caused 95% reduction of total pathogens only in 6–13% of similar study sites (P = 0.02). Reduction in mean pocket depth was 1.8 mm for the PVP‐iodine/scaling and root planing group, 1.6 mm for the scaling and root planing group, and 0.9 mm for the PVP‐iodine and the saline monotherapy groups, with statistical significance reached for the scaling and root planing group vs. the PVP‐iodine group (P = 0.04) and for the scaling and root planing group vs. the saline group (P = 0.02). Reduction in visible dental plaque, which ranged from 38% to 62%, showed no significant differences among treatment groups.

Conclusions: The addition of subgingival PVP‐iodine irrigation to conventional mechanical therapy may be a cost‐effective means of reducing total counts of periodontal pathogens and helping control periodontal disease. However, subgingival irrigation with PVP‐iodine without concomitant mechanical debridement might not improve microbiological and clinical variables in comparison with saline irrigation, at least not in sites with radiographic evidence of subgingival calculus.