bluuebunny/crossref_metadata_2025 huggingface dataset:
Eternal Recurrence in The Blind Owl
Authors: Cisco Michael
Published: August 2010

This article analyzes the surprisingly consistent way in which Sadeq Hedayat's novella, The Blind Owl, represents the concept of eternal recurrence. Hedayat employs repetition in a unique manner. Neither narrator ever remarks upon or seems to notice that events, motifs, and similar or identical epithets and phrasings which arise in their own thoughts and utterances are repeating, but they rather encounter every repeated event or thought as if it had only just occurred for the first time. While I do not claim that Hedayat was in any meaningful way a ‘Nietzschean’ thinker, philosophical ideas from Nietzsche's works and those of the French thinkers who came after, most notably Klossowski and Deleuze, interact strikingly with The Blind Owl and seem to bring hitherto unnoticed dimensions of this important work to our attention. Notably, Hedayat depicts a struggle with nihilism that is informed by the philosophical questions surrounding what came to be known as existentialism, but in a manner that is not merely derivative of European models.
Low expectations: does Italy factor into American foreign policy calculations?
Authors: Sperling James
Published: August 2010

The American attentive foreign policy elite's perceptions of Italy as a foreign policy actor appear inconsistent with Italy's global role. The paradox of Italy's global status as a middle-power and the absence of status within the American foreign policy community raises three questions: What role should we expect Italy to play in American foreign policy calculations given its structural position in the international system? What role does Italy play in aiding or hindering American foreign policy objectives within the transatlantic community? Is there a disjunction between the American elite's subjectively low expectations for Italy as a foreign policy actor and Italy's objective importance for the successful realisation of American foreign policy objectives?
A nice place to visit: Italy as seen by Canadians
Authors: Croci Osvaldo , Tossutti Livianna
Published: August 2010

This article analyses Canadian perceptions of Italy at the governmental and societal levels. It argues that Canadians pay relatively little attention to things Italian and that their images of Italy are somewhat stereotypical. Italian politics do not receive much attention and when they do, domestic political aspects prevail over foreign policy ones. The Canadian press represents Italy as a country with a cultural and artistic past, an economic system that finds it difficult to adjust to globalisation and hence destined to decline, a corrupt political system and last, but not least, a society exhibiting many curious, and even bizarre, streaks.
Germany's view of Italy in the new century: new challenges and old stereotypes
Authors: Diedrichs Udo
Published: August 2010

Italy's relationship with Germany has undergone substantial changes over the last 20 years. Since 1989, the two countries, traditional allies and partners in the EU and NATO, have experienced a number of tensions. A crucial problem for Germany lies in its incapacity to accept fully Italy's ambitions to be a leading European power. In domestic terms, the perception of Italy has been heavily overshadowed by the figure of Silvio Berlusconi who has allowed familiar stereotypes to survive and impeded a sober analysis of Italy's changed preferences.
‘Experts in truth?’: the politics of retribution in Italy and the role of historians
Authors: Pezzino Paolo
Published: August 2010

There have been many reflections on the relations between the judge and the historian which have concentrated on the differences between these two figures: but what happens in cases where an historian collaborates openly with a judge as an expert consultant? What happens when an investigative office, or a court, asks an historian to reconstruct an event which is subject to a judicial procedure, or when he or she has to pronounce the ‘last word’ on an event or a document? Or, in another possible scenario, what happens when a community asks an historian to pronounce on what happened in the past, in order to ascertain which, between two contesting memories of the representation of an event, is the one which corresponds to what ‘really happened’? In these cases historians are sought out to establish the truth–their professional skills as ‘truth experts’ are called upon. And there is an extraordinary faith that the truth will be discovered. The author reflects on these issues, using as a starting point his own personal experiences as a consultant in some recent Italian war-crimes trials.
Small Molecule Inhibition of HIV-1–Induced MHC-I Down-Regulation Identifies a Temporally Regulated Switch in Nef Action
Authors: Dikeakos Jimmy D. , Atkins Katelyn M. , Thomas Laurel , Emert-Sedlak Lori , Byeon In-Ja L. , Jung Jinwon , Ahn Jinwoo , Wortman Matthew D. , Kukull Ben , Saito Masumichi , Koizumi Hirokazu , Williamson Danielle M. , Hiyoshi Masateru , Barklis Eric , Takiguchi Masafumi , Suzu Shinya , Gronenborn Angela M. , Smithgall Thomas E. , Thomas Gary
Published: August 2010

HIV-1 Nef triggers down-regulation of cell-surface MHC-I by assembling a Src family kinase (SFK)-ZAP-70/Syk-PI3K cascade. Here, we report that chemical disruption of the Nef-SFK interaction with the small molecule inhibitor 2c blocks assembly of the multi-kinase complex and represses HIV-1–mediated MHC-I down-regulation in primary CD4+T-cells. 2c did not interfere with the PACS-2–dependent trafficking of Nef required for the Nef-SFK interaction or the AP-1 and PACS-1–dependent sequestering of internalized MHC-I, suggesting the inhibitor specifically interfered with the Nef-SFK interaction required for triggering MHC-I down-regulation. Transport studies revealed Nef directs a highly regulated program to down-regulate MHC-I in primary CD4+T-cells. During the first two days after infection, Nef assembles the 2c-sensitive multi-kinase complex to trigger down-regulation of cell-surface MHC-I. By three days postinfection Nef switches to a stoichiometric mode that prevents surface delivery of newly synthesized MHC-I. Pharmacologic inhibition of the multi-kinase cascade prevents the Nef-dependent block in MHC-I transport, suggesting the signaling and stoichiometric modes are causally linked. Together, these studies resolve the seemingly controversial models that describe Nef-induced MHC-I down-regulation and provide new insights into the mechanism of Nef action.
MetDAT: a modular and workflow-based free online pipeline for mass spectrometry data processing, analysis and interpretation
Authors: Biswas Ambarish , Mynampati Kalyan C. , Umashankar Shivshankar , Reuben Sheela , Parab Gauri , Rao Raghuraj , Kannan Velayutham S. , Swarup Sanjay
Published: August 2010

Summary: Analysis of high throughput metabolomics experiments is a resource-intensive process that includes pre-processing, pre-treatment and post-processing at each level of experimental hierarchy. We developed an interactive user-friendly online software called Metabolite Data Analysis Tool (MetDAT) for mass spectrometry data. It offers a pipeline of tools for file handling, data pre-processing, univariate and multivariate statistical analyses, database searching and pathway mapping. Outputs are produced in the form of text and high-quality images in real-time. MetDAT allows users to combine data management and experiment-centric workflows for optimization of metabolomics methods and metabolite analysis.

Availability: MetDAT is available free for academic use from http://smbl.nus.edu.sg/METDAT2/.

Contact:  sanjay@nus.edu.sg
Identifying informative subsets of the Gene Ontology with information bottleneck methods
Authors: Jin Bo , Lu Xinghua
Published: August 2010

Motivation: The Gene Ontology (GO) is a controlled vocabulary designed to represent the biological concepts pertaining to gene products. This study investigates the methods for identifying informative subsets of GO terms in an automatic and objective fashion. This task in turn requires addressing the following issues: how to represent the semantic context of GO terms, what metrics are suitable for measuring the semantic differences between terms, how to identify an informative subset that retains as much as possible of the original semantic information of GO.

Results: We represented the semantic context of a GO term using the word-usage-profile associated with the term, which enables one to measure the semantic differences between terms based on the differences in their semantic contexts. We further employed the information bottleneck methods to automatically identify subsets of GO terms that retain as much as possible of the semantic information in an annotation database. The automatically retrieved informative subsets align well with an expert-picked GO slim subset, cover important concepts and proteins, and enhance literature-based GO annotation.

Availability:  http://carcweb.musc.edu/TextminingProjects/

Contact:  xinghua@pitt.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Cross-species queries of large gene expression databases
Authors: Le Hai-Son , Oltvai Zoltán N. , Bar-Joseph Ziv
Published: August 2010

Motivation: Expression databases, including the Gene Expression Omnibus and ArrayExpress, have experienced significant growth over the past decade and now hold hundreds of thousands of arrays from multiple species. Since most drugs are initially tested on model organisms, the ability to compare expression experiments across species may help identify pathways that are activated in a similar way in humans and other organisms. However, while several methods exist for finding co-expressed genes in the same species as a query gene, looking at co-expression of homologs or arbitrary genes in other species is challenging. Unlike sequence, which is static, expression is dynamic and changes between tissues, conditions and time. Thus, to carry out cross-species analysis using these databases, we need methods that can match experiments in one species with experiments in another species.

Results: To facilitate queries in large databases, we developed a new method for comparing expression experiments from different species. We define a distance metric between the ranking of orthologous genes in the two species. We show how to solve an optimization problem for learning the parameters of this function using a training dataset of known similar expression experiments pairs. The function we learn outperforms previous methods and simpler rank comparison methods that have been used in the past for single species analysis. We used our method to compare millions of array pairs from mouse and human expression experiments. The resulting matches can be used to find functionally related genes, to hypothesize about biological response mechanisms and to highlight conditions and diseases that are activating similar pathways in both species.

Availability: Supporting methods, results and a Matlab implementation are available from http://sb.cs.cmu.edu/ExpQ/

Contact:  zivbj@cs.cmu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
NoiseMaker: simulated screens for statistical assessment
Authors: Kwan Phoenix , Birmingham Amanda
Published: August 2010

Summary: High-throughput screening (HTS) is a common technique for both drug discovery and basic research, but researchers often struggle with how best to derive hits from HTS data. While a wide range of hit identification techniques exist, little information is available about their sensitivity and specificity, especially in comparison to each other. To address this, we have developed the open-source NoiseMaker software tool for generation of realistically noisy virtual screens. By applying potential hit identification methods to NoiseMaker-simulated data and determining how many of the pre-defined true hits are recovered (as well as how many known non-hits are misidentified as hits), one can draw conclusions about the likely performance of these techniques on real data containing unknown true hits. Such simulations apply to a range of screens, such as those using small molecules, siRNAs, shRNAs, miRNA mimics or inhibitors, or gene over-expression; we demonstrate this utility by using it to explain apparently conflicting reports about the performance of the B score hit identification method.

Availability and implementation: NoiseMaker is written in C#, an ECMA and ISO standard language with compilers for multiple operating systems. Source code, a Windows installer and complete unit tests are available at http://sourceforge.net/projects/noisemaker. Full documentation and support are provided via an extensive help file and tool-tips, and the developers welcome user suggestions.

Contact:  amanda.birmingham@thermofisher.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
RBSDesigner: software for designing synthetic ribosome binding sites that yields a desired level of protein expression
Authors: Na Dokyun , Lee Doheon
Published: August 2010

Motivation: RBSDesigner predicts the translation efficiency of existing mRNA sequences and designs synthetic ribosome binding sites (RBSs) for a given coding sequence (CDS) to yield a desired level of protein expression. The program implements the mathematical model for translation initiation described in Na et al. (Mathematical modeling of translation initiation for the estimation of its efficiency to computationally design mRNA sequences with a desired expression level in prokaryotes. BMC Syst. Biol., 4, 71). The program additionally incorporates the effect on translation efficiency of the spacer length between a Shine–Dalgarno (SD) sequence and an AUG codon, which is crucial for the incorporation of fMet-tRNA into the ribosome. RBSDesigner provides a graphical user interface (GUI) for the convenient design of synthetic RBSs.

Availability: RBSDesigner is written in Python and Microsoft Visual Basic 6.0 and is publicly available as precompiled stand-alone software on the web (http://rbs.kaist.ac.kr).

Contact:  dhlee@kaist.ac.kr
Families' Perspectives on the Effect of Constipation and Fecal Incontinence on Quality of Life
Authors: Kaugars Astrida Seja , Silverman Alan , Kinservik Margo , Heinze Susan , Reinemann Lisa , Sander Megan , Schneider Brian , Sood Manu
Published: August 2010

Objectives:

Understanding families' quality of life can be important for interdisciplinary treatment planning. The present study examined child and parent perspectives about how constipation and fecal incontinence affect families' quality of life.

Patients and Methods:

Semistructured interviews were conducted with 8 children/adolescents and 8 caregivers. All of the children met Rome II criteria for functional constipation. Interviews were analyzed by an interdisciplinary team using a content analysis approach, which included developing a coding manual that described emergent themes from the interview transcripts.

Results:

Qualitative and quantitative responses revealed the varied experiences of participating families. Child and parent views may be misaligned, which can affect treatment planning and effectiveness. Families described variable satisfaction with the treatment recommendations they had been offered and experienced difficulty finding appropriate care. Children's social and family functioning were significantly affected by constipation and fecal incontinence difficulties. Both children and parents described the challenges of discussing the problems with others.

Conclusions:

Multiple domains of individual and family functioning are affected by children's constipation and fecal incontinence difficulties, thereby affecting the quality of life of both children and their parents. The findings underscore the need for providers to consider the influence of symptoms on adjustment to both the medical condition and treatment adherence and discuss concerns with children and parents. The results provide the foundation for developing a standardized tool for quantitative assessment of quality of life for children with constipation.
Response dynamics of phosphorelays suggest their potential utility in cell signalling
Authors: Csikász-Nagy Attila , Cardelli Luca , Soyer Orkun S.
Published: August 2010

Phosphorelays are extended two-component signalling systems found in diverse bacteria, lower eukaryotes and plants. Only few of these systems are characterized, and we still lack a full understanding of their signalling abilities. Here, we aim to achieve a global understanding of phosphorelay signalling and its dynamical properties. We develop a generic model, allowing us to systematically analyse response dynamics under different assumptions. Using this model, we find that the steady-state concentration of phosphorylated protein at the final layer of a phosphorelay is a linearly increasing, but eventually saturating function of the input. In contrast, the intermediate layers can display ultrasensitivity. We find that such ultrasensitivity is a direct result of the phosphorelay biochemistry; shuttling of a single phosphate group from the first to the last layer. The response dynamics of the phosphorelay results in tolerance of cross-talk, especially when it occurs as cross-deactivation. Further, it leads to a high signal-to-noise ratio for the final layer. We find that a relay length of four, which is most commonly observed, acts as a saturating point for these dynamic properties. These findings suggest that phosphorelays could act as a mechanism to reduce noise and effects of cross-talk on the final layer of the relay and enforce its input–response relation to be linear. In addition, our analysis suggests that middle layers of phosphorelays could embed thresholds. We discuss the consequence of these findings in relation to why cells might use phosphorelays along with enzymatic kinase cascades.
Moisture dynamics in walls: response to micro-environment and climate change
Authors: Hall Christopher , Hamilton Andrea , Hoff William D. , Viles Heather A. , Eklund Julie A.
Published: August 2010

A coupled sharp-front (SF) liquid transport and evaporation model is used to describe the capillary rise of moisture in monoliths and masonry structures. This provides a basis for the quantitative engineering analysis of moisture dynamics in such structures, with particular application to the conservation of historic buildings and monuments. We show how such a system responds to seasonal variations in the potential evaporation (PE) of the immediate environment, using meteorological data from southern England and Athens, Greece. Results from the SF analytical model are compared with those from finite-element unsaturated-flow simulations. We examine the magnitude and variation of the total flow through a structure as a primary factor in long-term damage caused by leaching, salt crystallization and chemical degradation. We find wide seasonal variation in the height of moisture rise, and this, together with the large estimated water flows, provides a new explanation of the observed position of salt-crystallization damage. The analysis also allows us to estimate the effects of future climate change on the capillary moisture dynamics of monoliths and masonry structures. For example, for southern England, predicted increases in PE for the period 2070–2100 suggest substantial increases in water flux, from which we expect increased damage rates.
Classical simulation of commuting quantum computations implies collapse of the polynomial hierarchy
Authors: Bremner Michael J. , Jozsa Richard , Shepherd Dan J.
Published: August 2010

We consider quantum computations comprising only commuting gates, known as IQP computations, and provide compelling evidence that the task of sampling their output probability distributions is unlikely to be achievable by any efficient classical means. More specifically, we introduce the class post-IQP of languages decided with bounded error by uniform families of IQP circuits with post-selection, and prove first that post-IQP equals the classical class PP. Using this result we show that if the output distributions of uniform IQP circuit families could be classically efficiently sampled, either exactly in total variation distance or even approximately up to 41 per cent multiplicative error in the probabilities, then the infinite tower of classical complexity classes known as the polynomial hierarchy would collapse to its third level. We mention some further results on the classical simulation properties of IQP circuit families, in particular showing that if the output distribution results from measurements on onlylines then it may, in fact, be classically efficiently sampled.
A congruent solution to arthropod phylogeny: phylogenomics, microRNAs and morphology support monophyletic Mandibulata
Authors: Rota-Stabelli Omar , Campbell Lahcen , Brinkmann Henner , Edgecombe Gregory D. , Longhorn Stuart J. , Peterson Kevin J. , Pisani Davide , Philippe Hervé , Telford Maximilian J.
Published: August 2010

While a unique origin of the euarthropods is well established, relationships between the four euarthropod classes—chelicerates, myriapods, crustaceans and hexapods—are less clear. Unsolved questions include the position of myriapods, the monophyletic origin of chelicerates, and the validity of the close relationship of euarthropods to tardigrades and onychophorans. Morphology predicts that myriapods, insects and crustaceans form a monophyletic group, the Mandibulata, which has been contradicted by many molecular studies that support an alternative Myriochelata hypothesis (Myriapoda plus Chelicerata). Because of the conflicting insights from published molecular datasets, evidence from nuclear-coding genes needs corroboration from independent data to define the relationships among major nodes in the euarthropod tree. Here, we address this issue by analysing two independent molecular datasets: a phylogenomic dataset of 198 protein-coding genes including new sequences for myriapods, and novel microRNA complements sampled from all major arthropod lineages. Our phylogenomic analyses strongly support Mandibulata, and show that Myriochelata is a tree-reconstruction artefact caused by saturation and long-branch attraction. The analysis of the microRNA dataset corroborates the Mandibulata, showing that the microRNAs miR-965 and miR-282 are present and expressed in all mandibulate species sampled, but not in the chelicerates. Mandibulata is further supported by the phylogenetic analysis of a comprehensive morphological dataset covering living and fossil arthropods, and including recently proposed, putative apomorphies of Myriochelata. Our phylogenomic analyses also provide strong support for the inclusion of pycnogonids in a monophyletic Chelicerata, a paraphyletic Cycloneuralia, and a common origin of Arthropoda (tardigrades, onychophorans and arthropods), suggesting that previous phylogenies grouping tardigrades and nematodes may also have been subject to tree-reconstruction artefacts.
Complete DNA barcode reference library for a country's butterfly fauna reveals high performance for temperate Europe
Authors: Dincă Vlad , Zakharov Evgeny V. , Hebert Paul D. N. , Vila Roger
Published: August 2010

DNA barcoding aims to accelerate species identification and discovery, but performance tests have shown marked differences in identification success. As a consequence, there remains a great need for comprehensive studies which objectively test the method in groups with a solid taxonomic framework. This study focuses on the 180 species of butterflies in Romania, accounting for about one third of the European butterfly fauna. This country includes five eco-regions, the highest of any in the European Union, and is a good representative for temperate areas. Morphology and DNA barcodes of more than 1300 specimens were carefully studied and compared. Our results indicate that 90 per cent of the species form barcode clusters allowing their reliable identification. The remaining cases involve nine closely related species pairs, some whose taxonomic status is controversial or that hybridize regularly. Interestingly, DNA barcoding was found to be the most effective identification tool, outperforming external morphology, and being slightly better than male genitalia. Romania is now the first country to have a comprehensive DNA barcode reference database for butterflies. Similar barcoding efforts based on comprehensive sampling of specific geographical regions can act as functional modules that will foster the early application of DNA barcoding while a global system is under development.
Host plant quality, selection history and trade-offs shape the immune responses ofManduca sexta
Authors: Diamond Sarah E. , Kingsolver Joel G.
Published: August 2010

Immune defences are an important component of fitness. Yet susceptibility to pathogens is common, suggesting the presence of ecological and evolutionary limitations on immune defences. Here, we use structural equation modelling to quantify the direct effects of resource quality and selection history, and their indirect effects mediated via body condition prior to an immune challenge on encapsulation and melanization immune defences in the tobacco hornworm,Manduca sexta. We also investigate allocation trade-offs among immune defences and growth rate following an immune challenge. We found considerable variation in the magnitude and direction of the direct effects of resource quality and selection history on immune defences and their indirect effects mediated via body condition and allocation trade-offs. Greater resource quality and evolutionary exposure to pathogens had positive direct effects on encapsulation and melanization. The indirect effect of resource quality on encapsulation mediated via body condition was substantial, whereas indirect effects on melanization were negligible. Individuals in better condition prior to the immune challenge had greater encapsulation; however, following the immune challenge, greater encapsulation traded off with slower growth rate. Our study demonstrates the importance of experimentally and analytically disentangling the relative contributions of direct and indirect effects to understand variation in immune defences.
Atomic resolution studies of haloalkane dehalogenases DhaA04, DhaA14 and DhaA15 with engineered access tunnels
Authors: Stsiapanava A. , Dohnalek J. , Gavira J. A. , Kuty M. , Koudelakova T. , Damborsky J. , Kuta Smatanova I.
Published: August 2010

The haloalkane dehalogenase DhaA fromRhodococcus rhodochrousNCIMB 13064 is a bacterial enzyme that shows catalytic activity for the hydrolytic degradation of the highly toxic industrial pollutant 1,2,3-trichloropropane (TCP). Mutagenesis focused on the access tunnels of DhaA produced protein variants with significantly improved activity towards TCP. Three mutants of DhaA named DhaA04 (C176Y), DhaA14 (I135F) and DhaA15 (C176Y + I135F) were constructed in order to study the functional relevance of the tunnels connecting the buried active site of the protein with the surrounding solvent. All three protein variants were crystallized using the sitting-drop vapour-diffusion technique. The crystals of DhaA04 belonged to the orthorhombic space groupP212121, while the crystals of DhaA14 and DhaA15 had triclinic symmetry in space groupP1. The crystal structures of DhaA04, DhaA14 and DhaA15 with ligands present in the active site were solved and refined using diffraction data to 1.23, 0.95 and 1.22 Å, resolution, respectively. Structural comparisons of the wild type and the three mutants suggest that the tunnels play a key role in the processes of ligand exchange between the buried active site and the surrounding solvent.
FS14.5 No suppression of nickel patch reactions by local betamethasone
Authors: Lauerma Antti , Molander Gerd , Petman Leena , Kannas Liisa
Published: August 2010

Background:  Topical corticosteroids are usually banned on test areas prior to patch testing. The previous literature on the effect of topical corticosteroids is conflicting.

Methods:  Patients allergic to nickel sulphate were patch tested on 4 sites with nickel on Day 0. Intracutaneous betamethasone was injected to test sites on Day −1, Day 0 and Day 1. NaCl injection on Day −1 was control. The patch test reactions were evaluated clinically and with laser doppler.

Observations:  There were no differences in patch test reaction intensities on sites treated with intracutaneous betamethasone as compared to control.

Conclusions:  A single local dose of potent corticosteroid does not suppress allergic patch reactions to nickel. The current practice of avoiding topical corticosteroid use prior to patch testing should be re‐evaluated.
FS14.6 Oral lichenoid reactions and amalgams: no topographical relationship
Authors: Pigatto Paolo , Passoni E , Crippa R , Tanzi C , Zerboni R , Brambilla L , Guzzi G , Muratori S
Published: August 2010

Background:  Several lines of evidence indicate a potential association between oral lichen‐reactions and the presence of dental amalgam fillings.

Aim:  We examined the relation between oral lichen reaction cases and the site of amalgam fillings in the oral cavity.

Methods:  We conducted an observational study in 5 consecutive patients who had OLR and underwent to dental amalgam replacement. The number of total amalgam surfaces and OLR sites were charted. Saliva samples were taken and levels of total mercury were measured by CV‐AAS method. Also we did patch‐testing with dental series in all patients. Results: Our observational study revealed that oral lichen reactions may not have an association with the physical proximity the mercury tooth fillings. Unexpectedly, we noted a complete remission in patients with OLR (n = 5). The patients with OLR presented allergies to mercury (n = 4) or gold (n = 1). All patients were negative for HCV/HBV and they had not been taking any drug‐induced lichenoid mucositis.

Findings:  In this case report series no topographical association was found between OLR and the dental amalgam fillings. All OLR cases were in full recovery after total amalgam removal within three months. Saliva mercury concentrations were significantly elevated in all subjects. After amalgam removal the mercury levels were undetectable. We suggest that dental amalgam removal is important therapeutic option in OLR cases even if the lichenoid lesions are not adjacent to dental amalgam restorations.
P05 Quantification of erythema using digital camera image analysis
Authors: Eun Hee‐Chul , Lee E , An S , Moon S , Cahang I
Published: August 2010

In general, Irritant skin reactions are graded by using visual scoring method for the degree of erythema, edema and scaling. The main disadvantage of this method lacks objectivity and parametric properties. The purpose of this study is to develop a quantitative evaluation method by using computerized color image analysis of skin erythema. We have described the objective measurement of the irritant skin responses by using skin surface color determination and compared it with the measurement by using traditional visual scoring method. Using R (Red), G (Green), B (Blue) value and CIE color parameters (L*a*b*) of digital camera image by using the software program, two kind of erythema index (ΔRG, Δab) and change in total color (ΔE*ab) were calculated. ΔRG value and Δab in digital camera image were highly correlated with the degree of erythema than chromameter measurements. And Δab (difference in color redness (a*) and yellow hue (b*)) with the exception of luminance (L* value) in CIE was well correlated than change in total color (ΔE*ab). Our data showed that erythema indices (ΔRG, Δab) were good parameters for evaluation of skin erythema produced by irritant reaction.
P06 Axillary irritation: methods of assessment
Authors: Peters L , Marriott Marie , Basketter DA
Published: August 2010

Axillary dermatitis can be associated with the use of underarm products. However the unique physiology of this region makes assessment of irritation problematic. Furthermore, given the type of products used in the underarm, the friction and occlusive nature of the site, it is necessary not only to concentrate on the area of application ie the area of hair growth, but also to examine the periphery. There is evidence that products tend to move to this area during the day possibly as a consequence of axillary physiology and mechanical effects. Consequent upon these various factors, predicting axillary irritation from acute patch tests on back or arm skin is problematic. In a recent comparison, we found that where approximately 10% of panellists reacted to a formulation by patch test, 50% developed axillary reactions during a 21 day use test. In addition, not all those who reacted in the patch test reacted in the axilla. Predicting axillary effects from repeated open tests seems better but still has challenges; currently we are assessing alternative strategies to permit rapid identification of potential issues without recourse to extended in use tests.
P09 Comparison between mild irritant response in haired and hairless guinea pigs
Authors: Andersen Flemming , Hedegaard Kathryn , Fullerton Ann
Published: August 2010

The hairless guinea pig offers the possibility of performing irritant studies without the use of depilatory agents or clipping. Studies have shown a response to allergens and simple irritants comparable to that of the haired guinea pig. Histoanatomical studies have demonstrated differences in cutaneous structure in the two strains, differences that might influence the response to mild irritants such as topical drug vehicles. The purpose of this study was to compare the usability of hairless (HLGP) and shaved haired guinea pigs (SGP) in tolerability studies of complex topical formulations. The tolerability of 6 selected skin care formulations (SCF), known to cause a differentiated irritative response in HLGP, was studied in 15 male SGP and 15 male HLGP. All animals were treated on a 5 × 5 cm area on each flank twice daily for 4 consecutive days with SCF. The irritant effects of the SCF were quantified clinically and by measurement of transepidermal water loss (TEWL) and colorimetry (a*‐parameter). Both species were able to differentiate between SCF in relation to skin tolerance and although the response pattern was somewhat different in the two species the ranking of the SCF was essentially the same using TEWL and clinical scoring. However, colorimetry was found to be unsuited for the evaluation of cutaneous irritation in the SGP over a period of days as regrowth of fur obfuscated the underlying erythema. In conclusion the HLGP appears to be a more suitable model for tolerability testing of composite formulations.
P11 The complex problem of sensitive skin
Authors: Basketter DA , Marriott Marie , Peters L , Cooper K , Holmes J
Published: August 2010

There exists within the population subsets of individuals who display heightened skin reactivity to materials the majority find tolerable. In a series of investigations, we have examined interrelationships between many of the endpoints associated with the term ‘sensitive skin’. In the most recent work, 58 volunteers were treated with 10% lactic acid, 50% ethanol, 0.5% menthol and 0.1% capsaicin on the nasolabial fold, unoccluded, for 8 minutes. Sensory reactions were recorded at 2.5, 5 and 8 minutes. Urticant susceptibility was evaluated with 1 M benzoic acid and 125 mM trans‐cinnamic acid applied to the volar forearm for 20 minutes. Visual assessments were taken at intervals for up to 4 hours after treatment. A 2 × 23 hour patch test was also conducted using 0.1% and 0.3% sodium dodecyl sulphate, 0.3% and 0.6% Tegobetain F50 and 0.1% and 0.2% benzalkonium chloride to determine irritant susceptibility. As found in previous studies, increased susceptibility to one endpoint was not predictive of sensitivity to another. In our hands, nasolabial stinging is a poor predictor of sensory as well general skin sensitivity. However, it may be possible to identify in the normal population individuals who are more generally sensitive to a range of non‐immunologic adverse skin reactions. Whether such individuals are those who experience problems with skin care products is open to question.
P15 A randomized double‐blind controlled trial comparing extra‐virgin coconut oil with mineral oil as a moisturizer for mild to moderate xerosis
Authors: Agero Anna Liza , Verallo‐Rowell V
Published: August 2010

Coconut oil, a traditional moisturizer used for centuries by people in the tropics, does not have any clinical studies documenting its effectivity and safety. This study aims to determine effectivity and safety of coconut oil compared to mineral oil as moisturizer for mild to moderate xerosis. A review board‐approved randomized double‐blind controlled trial was conducted in 34 patients after negative patch‐testing. Patients applied either coconut or mineral oil twice a day for two weeks. Quantitative outcomes for effectivity, measured at baseline and each weekly visit, were skin hydration (Corneometer CM825®) and skin lipids (Sebumeter SM810®); for safety, transepidermal water loss [TEWL](Tewameter TM210®) and skin surface pH (Skin pH meter PH900®). Patients and investigator evaluated symptoms of dryness, scaling, roughness, and pruritus using visual analogue scales (VAS) and grading of xerosis. Both groups showed significant improvement in skin hydration and increased skin surface lipid levels. TEWL and Skin pH were not affected. Objective instrumental determinations showed no significant difference between both groups. Patient and investigator subjective grading of xerosis and VAS showed general trend toward better, though not statistically evident, with coconut over mineral oil. Coconut oil is as effective and safe as mineral oil as a moisturizer.
P16 Eyelid dermatitis with positive patch test to coconut diethanolamide
Authors: Dejobert Yves , Delaporte E , Piette F , Thomas P
Published: August 2010

Objective:  The aim was to detect a possible allergen in a patient with eyelid dermatitis. Patient and methods: a non atopic 27‐year‐old female presented with eyelid dermatitis since 3 months. This dermatitis persisted despite the fact she had stopped the use of make up; she had acrylic artificial nails since 2 months and sometimes used hair dyes;patch tests were performed with Finn Chamber® tests with readings at D2 and D3, according ICDRG criteria, with European standard series, additional series (including toluenesulfonamide formaldehyde resin), cosmetic, acrylates, hairdressing series, in 3 patch test sessions, using Chemotechnique Diagnostics® allergens.

Results:  The only positive patch test was coconut diethanolamide (0.5% pet.)++ at D2 and D3. After removal of the shampoo containing this allergen, the dermatitis cleared. Coconut diethanolamide (cocamide DEA), tensioactive synthesized with coconut oil is widely used in shampoos, soaps, shower gels, barrier creams, washing up liquids, metalworking fluids, hydraulic oils. Involvement of eyelids is not frequently described in the literature with this allergen.

Conclusion:  Coconut diethanolamide should be added in cosmetic series, and it should be useful to test this allergen in patients with eyelid dermatitis.
P72 Pigmented patch‐test substance and laser Doppler perfusion imaging
Authors: Bjarnason Bolli , Flosadottir Ellen
Published: August 2010

Objective:  To investigate if pigment of a dark patch‐test substance may affect assessment of perfusion with the laser Doppler imaging technique.

Materials:  13 subjects who previously patch‐tested positive with 25% balsam of Peru in petrolatum were re‐tested with the same test substance and petrolatum controls applied directly by transparent foils and with much weaker and less pigmented serial doses tested with polyester squares. Readings of perfusion were performed through the test substances and the transparent foils at time intervals up to 4 days while tests were applied and for 5 days following detachment of tests. The instrument set‐up of the LDPI was the same as we have suggested for non‐pigmented patch‐test substances tested on white skin.

Results:  Results show that pigment remnants following detachment of the dark pigmented and pasty test substance containing the petrolatum vehicle were prone to affect perfusion assessments by masking detection of perfusion of parts of test sites. A real masking effect is supported by a similar effect with readings of the same tests while they were applied and by no such observable effect with the petrolatum controls or the non‐pasty and much less pigmented squares.

Conclusion:  The results show that pigment of patch‐test substances may affect perfusion assessments with the instrument set‐up suggested for non‐pigmented substances.
P74 Categorisation of human sensitisation potency using local lymph node assay EC3 values
Authors: Basketter David A , Gilmour N , Ryan C , Gerberick GF , Dearman R , Kimber I
Published: August 2010

Effective evaluation of skin sensitisation demands that potential contact allergens are identified and the risk of sensitisation amongst exposed populations assessed. Sensitisation hazard is not an all or nothing phenomenon; dose response relationships can be discerned and thresholds identified for induction and elicitation of contact allergy. These parameters, under the heading of potency, are vital for the risk assessment process. The murine local lymph node assay (LLNA) is an accepted method for the identification of sensitisation hazards (a sensitiser is a chemical that induces a stimulation index 3 or more times that of the concurrent vehicle control). The LLNA has also been used to determine the potency of sensitisers, by derivation of an EC3 value, the estimated concentration of chemical required to induce a stimulation index of 3. At present, various agencies, including in EU and OECD, together with industry bodies, are considering whether and how to adapt these data into regulations which would place sensitisers into one of several potency categories. It is our view, based on an evaluation of over 300 chemicals, that five categories: extreme, strong, moderate, weak and negative represent the optimal approach and is consistent with what is understood regarding the potency of these skin sensitisers in humans. To illustrate this approach, an example dataset of 100 selected organic chemicals is shown, where the accuracy of prediction of human potency is in the region of 90%. This categorisation has utility as a simple guide for risk management strategies as well as representing an important first step in risk assessment.
P77 Incidence of psoriasis in Norway
Authors: Selvaag Edgar , Loeb M
Published: August 2010

Investigations in several western countries, especially european, have shown an increase in the frequency of psoriasis. To investigate these trends in Norway, the following procedure was followed.

Using four standardized interview‐reports the development and the frequency of atopic dermatitis was determined.

The questionnaires were conducted in the years 1968, 1975, 1985 and 1995. The results were registred electronically, and made available on the Statistical Package for the Social Sciences (SPSS) in Windows version.

In 1968 420 out of 11101 persons suffered from a skin disease, in 1975 the number had increased to 690 out of 11014 persons. These numbers still increased; in 1985 1136 out of 10576 and in 1995 1026 out of 10248 said to suffer from a skin disease.

The diagnosis psoriasis was reported by 34 persons in 1968 (8% of all skin disease), increased to 97 in 1975 (14.1%), to 149 in 1985 (13.1%), and finally to 284 in 1995 (26.7%).

In all, the infectious skin diseases decreased in number, whereas inflammatory skin diseases, such as psoriasis but also atopic dermatitis increased.

Connections to air pollution, indoor environment, especially smoking are at present under investigation.

These results indicate that psoriasis is among the most frequent skin diseases in Norway, comparable to other western industrialized countries.
P79 A chemical dataset for evaluation of alternative approaches to skin sensitization testing
Authors: Kern Petra S , Patlewicz GY , Dearman RJ , Ryan CA , Kimber I , Basketter DA , Gerberick GF
Published: August 2010

In recent years, the local lymph node assay (LLNA) has emerged as a practical option for assessing the skin sensitization potential of chemicals. In addition to accurate identification of skin sensitizers, the LLNA can also provide a reliable measure of relative sensitization potency; information that is pivotal in successful management of human health risks. However, even with the significant animal welfare benefits provided by the LLNA, there is interest still in the development of non‐animal test methods for skin sensitization. Here, we have collected a large dataset of chemicals that have been tested in the LLNA, and the activity of which correspond with what is known of their potential to cause skin sensitization in humans. It is anticipated that this will be of value to other investigators in the evaluation and calibration of novel approaches to skin sensitization testing, in particular for the development of in silico methods. Prerequisite for the development of in silico models is always the availability of a large high quality data set, suitable for modeling. This dataset encompasses both the chemical and biological diversity of known chemical allergens, and provides also examples of negative controls. The data are a collection of published and non‐proprietary industry data. All materials were tested in standard vehicules following the standard LLNA protocol. It is hoped that this dataset will accelerate the development, evaluation and eventual validation of new approaches to skin sensitization testing.
P80 Preliminary findings on the histopathology of chronic hand dermatitis
Authors: Willis Carolyn , Britton L , Orton D
Published: August 2010

Chronic hand dermatitis is a common and distressing condition with a complex, multifactorial aetiology. In order to better understand its pathophysiology and hopefully improve diagnosis, we have begun a systematic histopathological study of various forms of hand dermatitis, with a particular emphasis on those in which exposure to irritants and allergens is strongly implicated. Suitable patients were recruited from amongst those presenting at the contact dermatitis clinic. Detailed past and present medical and personal histories, clinical examination, patch testing and prick testing were conducted in order to classify the eczema into one of several broad entities e.g. chronic irritant contact dermatitis (CICD), with or without atopy. After performing a range of bio‐engineering measurements on a pre‐selected affected area of the hand, biopsies were removed and processed for high resolution light microscopy and immunocytochemistry. Age/sex matched, healthy, non‐atopic individuals provided control skin from similar sites of the hand. Using a range of antibodies and quantification techniques, we examined the status and expression of certain immune‐associated cells and receptor/adhesion molecules. Of note amongst these, were the differences in epidermal CD1a+ cell density between groups. Non‐atopics with CICD, for example, had significantly fewer CD1a+ cells than both atopics with CICD and those with normal skin. CD54 (ICAM‐1) and several cytokine/chemokine receptors were more widely and strongly expressed by keratinocytes in those with an atopic diathesis. Although preliminary in nature at this stage, our results suggest that different forms of hand dermatitis display characteristic immunopathological features which may possibly be of diagnostic value.