bluuebunny/crossref_metadata_2025 huggingface dataset:
Routinizing the offshore choice: applying diffusion of innovation to the case of EDS
Authors: Carmel Erran , Dedrick Jason , Kraemer Kenneth L.
Published: November 2009

Purpose

We treat offshoring as a managerial innovation. Should it still be considered an innovation? The purpose of this paper is to use innovation theory, especially, Rogers' diffusion of innovation theory (DOI) to examine this question.

Design/methodology/approach

The paper examines the case of electronic data systems (EDS), a very large Information Technology Professional Services (ITPS) company, using a case study approach based on interviews, internal documents and secondary sources.

Findings

At EDS it was found that offshoring has been fully assimilated within just a few years. During the early 2000s, EDS faced the challenge of a large‐scale shift in the competitive landscape and moved a large share of its global operations to offshore locations. The paper shows how this innovation has been diffused within the firm through the creation of an assessment and migration organization that has institutionalized and routinized the process of offshoring. At EDS, each client project goes through a centralized offshoring assessment process to determine where best to send the work and how to perform the knowledge transfer quickly and effectively. Observations are made about the speed of diffusion: about 7‐10 years in this case, from initial innovation agenda setting to its routinization.

Research limitations/implications

This paper filled a gap in studying managerial innovation; made some estimates of the speed of diffusion; and applied the hypothesized stages of innovation diffusion to the context of offshore software services. The limitation is that this is a case study and therefore generalization may be qualified.

Originality/value

This paper is among the first that studies offshoring (as opposed to outsourcing) in terms of DOI theory.
Managing change in IT outsourcing arrangements
Authors: Plugge Albert , Janssen Marijn
Published: November 2009

Purpose

Clients and IT outsourcing service providers are regularly confronted with changes in their business and IT environment. This paper aims at understanding the need for adaptability and the capabilities of service providers in outsourcing arrangements.

Design/methodology/approach

The paper uses a combination of literature research and case study research. A retrospective view on the case study was investigated using interviews, and analyses of reports and observations.

Findings

Clients are dependent on their service providers to adapt to changes and their service providers can help to better deal with their ever‐changing environment. This case study shows that the level of adaptability of service providers affects their sourcing capabilities, which results in improved customer retention by service providers and in their clients gaining competitive advantage. Service providers can create adaptability by developing their organizational capabilities, specifically by managing relationships and developing procedures for dealing with change.

Research limitations/implications

As the aim was to improve the understanding, an explorative, single case study was performed. More detailed research of the various factors influencing the level of adaptability of services providers is recommended. Multiple case studies are recommended to gain a more in‐depth overview of a variety of causes and effects in different situations.

Practical implications

For outsourcing service providers this study suggests that they should create and continuously evaluate capabilities to remain competitive. In the case study the offshore service provider gained a larger share of the outsourced business. Furthermore, contracts are more likely to be extended. This research suggests that the service provider's ability to adapt should be part of the sourcing decision process of clients. During both the sourcing strategy and the tender selection phase, clients can identify to what extent an outsourcing partner will cater for environmental uncertainty.

Originality/value

The role of service providers in outsourcing arrangements has received only limited research attention so far. Furthermore, adaptability in sourcing arrangements has hardly been investigated at all.
Customer perception on service quality in retail banking in Middle East: the case of Qatar
Authors: Hossain Mohammed , Leo Shirley
Published: November 2009

Purpose

The purpose of this paper is to evaluate the service quality in retail banking in the Middle East in general, and Qatar in particular, based on different levels of customers' perception regarding service quality.

Design/methodology/approach

This is an analytical study based mainly on the primary data collected through a scientifically developed questionnaire. The questionnaire have been personally administered on a sample size of 120, chosen on a convenient basis from four Qatari banks, i.e. Qatar National Bank, Doha Bank, Qatar International Islamic Bank, and Arab Bank. The questionnaire has been designed on the basis of the study of previous scholars such as Berry et al., Parasuraman et al., Zeithaml and Bitner, and Stafford.

Findings

The result indicates that customers' perception is highest in the tangibles area and lowest in the competence area.

Practical implications

In order to achieving higher levels of quality service in retail banking, banks should deliver higher levels of service quality and in the present context customers' perceptions are highest in the level of infrastructure facilities of the bank, followed by timing of the bank, and return on deposit. Owing to the increasing competition in retail banking, customer service is an important part and bank managers should be rethinking how to improve customer satisfaction with respect to service quality.

Originality/value

This paper makes a useful contribution given that there are only a few studies dealing with the assessment of service quality in banking environments.
Shifts in species and phylogenetic diversity between sapling and tree communities indicate negative density dependence in a lowland rain forest
Authors: Gonzalez Mailyn A. , Roger Aurélien , Courtois Elodie A. , Jabot Franck , Norden Natalia , Paine C. E. Timothy , Baraloto Christopher , Thébaud Christophe , Chave Jérôme
Published: November 2009

1. As trees in a given cohort progress through ontogeny, many individuals die. This risk of mortality is unevenly distributed across species because of many processes such as habitat filtering, interspecific competition and negative density dependence. Here, we predict and test the patterns that such ecological processes should inscribe on both species and phylogenetic diversity as plants recruit from saplings to the canopy.

2. We compared species and phylogenetic diversity of sapling and tree communities at two sites in French Guiana. We surveyed 2084 adult trees in four 1‐ha tree plots and 943 saplings in sixteen 16‐m2 subplots nested within the tree plots. Species diversity was measured using Fisher’s alpha (species richness) and Simpson’s index (species evenness). Phylogenetic diversity was measured using Faith’s phylogenetic diversity (phylogenetic richness) and Rao’s quadratic entropy index (phylogenetic evenness). The phylogenetic diversity indices were inferred using four phylogenetic hypotheses: two based on rbcLa plastid DNA sequences obtained from the inventoried individuals with different branch lengths, a global phylogeny available from the Angiosperm Phylogeny Group, and a combination of both.

3. Taxonomic identification of the saplings was performed by combining morphological and DNA barcoding techniques using three plant DNA barcodes (psbA‐trnH, rpoC1 and rbcLa). DNA barcoding enabled us to increase species assignment and to assign unidentified saplings to molecular operational taxonomic units.

4. Species richness was similar between saplings and trees, but in about half of our comparisons, species evenness was higher in trees than in saplings. This suggests that negative density dependence plays an important role during the sapling‐to‐tree transition.

5. Phylogenetic richness increased between saplings and trees in about half of the comparisons. Phylogenetic evenness increased significantly between saplings and trees in a few cases (4 out of 16) and only with the most resolved phylogeny. These results suggest that negative density dependence operates largely independently of the phylogenetic structure of communities.

6. Synthesis. By contrasting species richness and evenness across size classes, we suggest that negative density dependence drives shifts in composition during the sapling‐to‐tree transition. In addition, we found little evidence for a change in phylogenetic diversity across age classes, suggesting that the observed patterns are not phylogenetically constrained.
Sexually antagonistic co‐evolution: a model and an empirical test
Authors: HOYLE A. , GILBURN A. S.
Published: November 2009

Models reveal that sexually antagonistic co‐evolution exaggerates female resistance and male persistence traits. Here we adapt an established model by including directional sexual selection acting against persistence. We find similar equilibria to previous models showing that sexually antagonistic co‐evolution can be limited by counteracting sexual, as well as, natural selection. We tested the model using empirical data for the seaweed fly, Coelopa ursina, in which body size acts as a persistence and a resistance trait. Our model can generate continuous co‐evolutionary cycles and stable equilibria, however, all simulations using empirically derived parameter estimates reach stable equilibria. Thus, stable equilibria might be more common in nature than continuous co‐evolutionary cycles, suggesting that sexual conflict is unlikely to promote speciation. The model predicts male biased sexual size dimorphism for C. ursina, comparable with empirically observed values. Male persistence is shown to be more sensitive than female resistance to changes in model parameters.
Calcium‐dependent physiological processes in trees
Authors: Lautner S. , Fromm J.
Published: November 2009

Among the various plant nutrients, calcium appears to occupy a unique position, acting as an important regulator in many processes related to both growth and responses to environmental stresses. This applies to stomatal function, cell division, cell wall synthesis, signalling functions in plant defence, repair of damage from biotic and abiotic stress and to the structural chemistry and function of woody tissues. The calcium content in the cambium of poplar was shown to rise transiently by as much as 40% in spring, indicating the significant role that calcium plays in the onset of cambial reactivation. Moreover, during bud flush and the beginning of cell division, calcium was reported to increase significantly in the apical meristem. A reduction in calcium supplies also proved to strongly affect wood formation, as evidenced in the pronounced reduction in wood increment, vessel size and fibre length, as well as in reduced carbonyl and methoxy groups from S‐lignin. Induced wounding revealed that calcium acts as an intracellular signal and, furthermore, proved its involvement in long‐distance electrical signalling. Environmental stimuli such as cold shock or wounding showed that poplar grown under calcium‐starved conditions was incapable of responding to this type of stress. The above evidence highlights the important role of calcium in tree functions, both as a signal in minute physiologically active pools within the cytoplasm, and in higher concentrations for its impact on the structural integrity of cell walls and woody tissues.
Book review
Authors: Gandhi Kanchan
Published: November 2009

Book reviewed in this issue.

On Disasters in India
 Anu Kapur
Do Exporting Firms Pay Higher Wages? Evidence from Kenya's Manufacturing Sector
Authors: Were Maureen , Kayizzi‐Mugerwa Steve
Published: November 2009

Abstract:  When trade liberalization was first embarked on in Kenya some 20 years ago, a key argument against it was that it would reduce domestic wages, as exporting firms sought to remain competitive versus, for example, the low‐cost Asian countries. A counter argument was that manufactured exports require more elaborate design, supervision, packaging and handling, and thus a more educated labor force than production for the domestic market. To attract such skills, exporting firms would need to pay higher wages than non‐exporting ones. This paper uses data from Kenyan manufacturing to study the impact of trade liberalization on earnings, distinguishing between exporting and non‐exporting firms. In particular, it investigates whether exporting firms paid a wage‐premium to their employees. The study uses manufacturing firm survey data from a World Bank regional project. The study has three important findings: (1) There was a large and significant effect of exporting on wages in the first decade of trade liberalization. During the first half of the 1990s, workers in exporting firms earned up to 30 percent more than those engaged in non‐exporting firms. The results are robust even after controlling for individual and firm‐level characteristics such as employee demographics, productivity, firm location and occupation. (2) After a decade of trade liberalization, exporting ceased to be a significant determinant of wages in Kenyan manufacturing, after controlling for productivity and firm location. (3) During the 2000s, casual or irregular employment became a more common feature of exporting firms. The results suggest that while higher wages were important in attracting skilled labor to exporting firms at the beginning of trade liberalization in the 1990s, domestic competition has since reduced the wage premium. Cost cutting pressures are instead reflected in the substitution of casual and low wage labor for permanent and better educated labor and in increased automation.
Determinants of Demand for Delivery Services in Sudan: An Empirical Investigation with Reference to Khartoum State, 2004*
Authors: Ahmed Huda Mohammed Mukhtar , Mahran Hatim Ameer
Published: November 2009

Abstract:  Using multinomial logistic methods, we examined the determinants of the delivery care seeking behavior of women in Khartoum State of Sudan, as well as the impact of changes in the attributes of public delivery services on the market shares of delivery services. Time distance and transportation cost have significant negative effects, while the random ‘quality’ coefficient is positive but not significantly different from zero. Further, the likelihood of choosing home over public delivery services increases with order of birth. The positive effects of women's education and household income are most important for those who prefer private over home delivery whereas the use of modern antenatal services is decisive in choosing modern over home delivery. Also, shifts in demand toward public delivery services resulting from improvements in quality and qualifications of medical staff might be undermined by the reduction in demand emanating from a rise in the order of delivery, time distance and transportation cost to public delivery institutions. The income effects are more pronounced, particularly for the share of private delivery services. Educated women tend to shift from home to modern delivery services.
Long‐term Determinants of Deforestation in Ghana: The Role of Structural Adjustment Policies
Authors: Codjoe Samuel Nii Ardey , Dzanku Fred M.
Published: November 2009

Abstract:  Prior to the 1980s, Ghana witnessed an alternating cycle of boom and scarcity, culminating in the introduction of structural adjustment policies in the early 1980s. This paper uses data from the Ghana Forestry Services, Ministry of Food and Agriculture, FAO Yearbook of Forestry Products, Ghana Timber Marketing Board, Quarterly Digest of the Ghana Statistical Service, World Debt Tables, Bank of Ghana, IMF, COCOBOD and Ministry of Finance to examine the impact of SAP on deforestation in Ghana. The paper reveals a negative impact of structural adjustment on deforestation in Ghana through both direct and indirect channels. The most important channel of the effect of SAP on deforestation resulted from the conversion of forestland to crop farming, particularly cocoa farming, during the post‐adjustment period. Even though wood extraction exhibited a negative impact on deforestation, the impact seemed relatively weaker than that of agricultural land use. In addition, while in the long run, deforestation tended to be more responsive to logging than agriculture, in the short run the elasticity of deforestation with respect to agriculture tended to be greater than that with respect to logging. Finally, agriculture was relatively more important in causing deforestation.
Genetic divergence between morphologically and acoustically cryptic bats: novel niche partitioning or recent contact?
Authors: Sedlock J. L. , Weyandt S. E.
Published: November 2009

Molecular tools have confirmed the presence of morphologically cryptic bat species initially detected by divergent echolocation calls. Here we document the presence of two sympatric, genetically distinct populations of bats whose echolocation calls were similar in peak frequency. They differed only slightly with respect to size, skull and wing morphology, and noseleaf shape, but the individuals, all initially identified as Rhinolophus arcuatus, fell into two groups exhibiting 3–4% sequence divergence in the cytochrome b gene. The coexistence of cryptic bats with only modest echolocation and physical differences challenges our understanding of niche partitioning in rhinolophid bats and suggests the possibility that a novel mode of niche partitioning may be used. Alternatively, their distributions may have only recently intersected as a result of forest loss, especially in the lowlands.
OBCAM, an immunoglobulin superfamily cell adhesion molecule, regulates morphology and proliferation of cerebral astrocytes
Authors: Sugimoto Chiaki , Maekawa Shohei , Miyata Seiji
Published: November 2009

J. Neurochem. (2010) 112, 830–839.

Opioid‐binding cell adhesion molecule (OBCAM) is a member of the immunoglobulin superfamily. In the present study, we investigated the expression and functional significance of OBCAM in cerebral astrocytes in vitro and in vivo. The confocal microscopic study revealed that the expression of OBCAM was prominent at filopodia and cellular processes of type‐1 and ‐2 astrocytes. Moreover, the expression of OBCAM was shown to be stronger at the growth phase than the stationary one in type‐1 ones. Ki‐67‐positive proliferating type‐1 astrocytes showed higher frequency of OBCAM expression as compared with Ki‐67‐negative cells. The application of the anti‐OBCAM IgG facilitated the proliferation of type‐1 astrocytes at relatively low concentration (1 and 5 μg/mL) and had no effects at relatively high concentration (25 and 50 μg/mL). The cellular proliferation was not promoted when the anti‐OBCAM Fab fragment was used, indicating that the antibody‐induced clustering of OBCAM promotes the proliferation. The over‐expression of OBCAM increased the cell size of type‐1 astrocytes. Moreover, intense expression of OBCAM was observed on reactive astrocytes in the injured cerebrum in vivo. These results suggest that OBCAM is responsible for controlling the cell proliferation and growth in cortical astrocytes.
Inhibition of myosin light chain kinase reduces brain edema formation after traumatic brain injury
Authors: Luh Clara , Kuhlmann Christoph R. , Ackermann Bianca , Timaru‐Kast Ralph , Luhmann Heiko J. , Behl Christian , Werner Christian , Engelhard Kristin , Thal Serge C.
Published: November 2009

J. Neurochem. (2009) 112, 1015–1025.

The role of the endothelial contractile apparatus in the process of brain edema formation after brain trauma is not characterized. Phosphorylation of myosin light chains by myosin light chain kinases (MLCK) activates endothelial contractile elements and results in a rearrangement of the cytoskeleton. This may enhance post‐traumatic blood‐brain barrier dysfunction. In order to investigate the role of the MLCK on brain edema formation and blood‐brain barrier permeability after brain injury, mice were anesthetized and subjected to a controlled cortical impact (CCI). MLCK expression is significantly up‐regulated after CCI with a maximum 12 h post‐injury. Specific inhibition of MLCK by ML‐7 resulted in a reduction of phosphorylation of myosin light chains and improved blood‐brain‐barrier integrity. Accordingly, ML‐7 attenuated post‐traumatic brain edema formation and intracranial hypertension 24 h after CCI. Prevention of brain edema formation did not translate into improved neurological outcome or reduced brain lesion. In conclusion, the results confirm that the endothelial contractile apparatus is activated by CCI and opens the endothelial barrier leading to vasogenic brain edema formation. Lack of neurological and histological improvement suggests that specific targeting of vasogenic brain edema at the endothelial level is not sufficient to limit secondary brain damage and has, therefore, to be combined with other potential neuroprotective strategies.
Positive allosteric modulation of α7 neuronal nicotinic acetylcholine receptors: lack of cytotoxicity in PC12 cells and rat primary cortical neurons
Authors: Hu Min , Gopalakrishnan Murali , Li Jinhe
Published: November 2009

Background and purpose:  α7‐Nicotinic acetylcholine receptors (α7 nAChRs) play an important role in cognitive function. Positive allosteric modulators (PAMs) amplify effects of α7 nAChR agonist and could provide an approach for treatment of cognitive deficits in neuropsychiatric diseases. PAMs can either predominantly affect the apparent peak current response (type I) or increase both the apparent peak current response and duration of channel opening, due to prolonged desensitization (type II). The delay of receptor desensitization by type II PAMs raises the possibility of Ca2+‐induced toxicity through prolonged activation of α7 nAChRs. The present study addresses whether type I and II PAMs exhibit different cytotoxicity profiles.

Experimental approach:  The present studies evaluated cytotoxic effects of type I PAM [N‐(4‐chlorophenyl)]‐α‐[(4‐chloro‐phenyl)‐aminomethylene]‐3‐methyl‐5‐isoxazoleacet‐amide (CCMI) and type II PAM 1‐[5‐chloro‐2,4‐dimethoxy‐phenyl]‐3‐[5‐methyl‐isoxazol‐3‐yl]‐urea (PNU‐120596), or 4‐[5‐(4chloro‐phenyl)‐2‐methyl‐3‐propionyl‐pyrrol‐1‐yl]‐benzenesulphonamide (A‐867744). The studies used cultures of PC12 cells and primary cultures of rat cortical neuronal cells.

Key results:  Our results showed that neither type I nor type II PAMs had any detrimental effect on cell integrity or cell viability. In particular, type II PAMs did not affect neuron number and neurite outgrowth under conditions when α7 nAChR activity was measured by Ca2+ influx and extracellular signal‐regulated kinases 1 and 2 phosphorylation, following exposure to α7 nAChR agonists.

Conclusions and implications:  This study demonstrated that both type I and type II α7 nAChR selective PAMs, although exhibiting differential electrophysiological profiles, did not exert cytotoxic effects in cells endogenously expressing α7 nAChRs.
Role of the signal peptide in the synthesis and processing of the glucagon‐like peptide‐1 receptor
Authors: Huang Y , Wilkinson GF , Willars GB
Published: November 2009

Background and purpose:  The glucagon‐like peptide‐1 receptor (GLP‐1R) belongs to Family B of the G protein‐coupled receptor superfamily and is a target for treatment of type 2 diabetes. Family B G protein‐coupled receptors contain a putative N‐terminal signal peptide, but its role in receptor synthesis and trafficking are unclear. Further, the signal peptide is not cleaved in at least one family member.

Experimental approach:  We examined receptor glycosylation and the role of the signal peptide in GLP‐1R synthesis and trafficking using constructs containing epitope tags at the N‐ and/or C‐terminus and in which the signal peptide sequence was either present or absent.

Key results:  The signal peptide was absolutely required for GLP‐1R synthesis but could be substituted to some extent by increasing positive charge in the N‐terminal region of the receptor flanking the signal peptide. The signal peptide is cleaved during synthesis and processing of the receptor. An enhanced GFP‐epitope tag at the N‐terminus of the receptor permitted synthesis of the receptor but blocked signal peptide cleavage and prevented trafficking to the plasma membrane. Cleavage site mutation allowed synthesis of a full‐length receptor, blocked signal peptide cleavage and caused retention within the endoplasmic reticulum.

Conclusions and implications:  Signal peptide cleavage was not essential for receptor synthesis but was obligatory for processing and trafficking of receptors to the plasma membrane. Further, the GLP‐1R is subject to N‐linked glycosylation and only the mature, fully glycosylated form of the receptor is present in the plasma membrane. Inhibition of glycosylation prevents processing and cell surface expression of the GLP‐1R.
Vascular endothelial growth factor and substrate mechanics regulate in vitro tubulogenesis of endothelial progenitor cells
Authors: Hanjaya‐Putra Donny , Yee Jane , Ceci Doug , Truitt Rachel , Yee Derek , Gerecht Sharon
Published: November 2009

Endothelial progenitor cells (EPCs) in the circulatory system have been suggested to maintain vascular homeostasis and contribute to adult vascular regeneration and repair. These processes require that EPCs break down the extracellular matrix (ECM), migrate, differentiate and undergo tube morphogenesis. Evidently, the ECM plays a critical role by providing biochemical and biophysical cues that regulate cellular behaviour. Using a chemically and mechanically tunable hydrogel to study tube morphogenesis in vitro, we show that vascular endothelial growth factor (VEGF) and substrate mechanics co‐regulate tubulogenesis of EPCs. High levels of VEGF are required to initiate tube morphogenesis and activate matrix metalloproteinases (MMPs), which enable EPC migration. Under these conditions, the elasticity of the substrate affects the progression of tube morphogenesis. With decreases in substrate stiffness, we observe decreased MMP expression while increased cellular elongation, with intracellular vacuole extension and coalescence to open lumen compartments. RNAi studies demonstrate that membrane type 1‐MMP (MT1‐MMP) is required to enable the movement of EPCs on the matrix and that EPCs sense matrix stiffness through signalling cascades leading to the activation of the RhoGTPase Cdc42. Collectively, these results suggest that coupled responses for VEGF stimulation and modulation of substrate stiffness are required to regulate tube morphogenesis of EPCs.
BCR‐ABL‐independent and RAS / MAPK pathway‐dependent form of imatinib resistance in Ph‐positive acute lymphoblastic leukemia cell line with activation of EphB4
Authors: Suzuki Momoko , Abe Akihiro , Imagama Shizuka , Nomura Yuka , Tanizaki Ryohei , Minami Yosuke , Hayakawa Fumihiko , Ito Yoshie , Katsumi Akira , Yamamoto Kazuhito , Emi Nobuhiko , Kiyoi Hitoshi , Naoe Tomoki
Published: November 2009

Objective: We investigated the mechanism responsible for imatinib (IM) resistance in Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ ALL) cell lines. Methods: We established cell lines from a patient with Ph+ ALL at the time of first diagnosis and relapsed phase and designated as NPhA1 and NPhA2, respectively. We also derived IM‐resistant cells, NPhA2/STIR, from NPhA2 under gradually increasing IM concentrations. Results: NPhA1 was sensitive to IM (IC50 0.05 μm) and NPhA2 showed mild IM resistance (IC50 0.3 μm). NPhA2/STIR could be maintained in the presence of 10 μm IM. Phosphorylation of MEK and ERK was slightly elevated in NPhA2 and significantly elevated in NPhA2/STIR compared to NPhA1 cells. After treatment with IM, phosphorylation of MEK and ERK was not suppressed but rather increased in NPhA2 and NPhA2/STIR. Active RAS was also increased markedly in NPhA2/STIR after IM treatment. The expression of BCL‐2 was increased in NPhA2 compared to NPhA1, but no further increase in NPhA2/STIR. Proliferation of NPhA2/STIR was significantly inhibited by a combination of MEK inhibitor and IM. Analysis of tyrosine phosphorylation status with a protein tyrosine kinase array showed increased phosphorylation of EphB4 in NPhA2/STIR after IM treatment. Although transcription of EphB4 was suppressed in NPhA1 and NPhA2 after IM treatment, it was not suppressed and its ligand, ephrinB2, was increased in NPhA2/STIR. Suppression of EphB4 transcripts by introducing short hairpin RNA into NPhA2/STIR partially restored their sensitivity to IM. Conclusions: These results suggest a new mechanism of IM resistance mediated by the activation of RAS/MAPK pathway and EphB4.
Epigenetic inactivation of tumour suppressor gene KLF11 in myelodysplastic syndromes*
Authors: Potapova Anna , Hasemeier Britta , Römermann Daniel , Metzig Kathleen , Göhring Gudrun , Schlegelberger Brigitte , Länger Florian , Kreipe Hans , Lehmann Ulrich
Published: November 2009

The identification of aberrantly hypermethylated genes may lead to the development of new diagnostic markers and the identification of novel targets of epigenetic therapy in myelodysplastic syndromes (MDS). We therefore investigated the methylation status of transcription factor genes KLF5, KLF11, and MAFB, shown to be aberrantly methylated in myelogeneous leukaemia cells, in a series of 115 MDS patient as well as in 25 control subjects. Using quantitative high‐resolution pyrosequencing methodology, KLF11, MAFB, and KLF5 were shown for the first time to be hypermethylated in 17 (15%), 8 (7%), and 2 (1.7%) cases, respectively, but not in any of the patients with an isolated 5q‐deletion. Patient samples harbouring KLF11 methylation displayed reduced KLF11 mRNA expression and KLF11 hypermethylation correlated with a high International Prognostic Scoring System score (P < 0.05). In conclusion, epigenetic inactivation and subsequent transcriptional repression of the KLF11 gene is quite frequent in MDS. Patients with an isolated 5q‐deletion seem to harbour a distinct epigenetic profile.
Secondary old‐field succession in an ecosystem with restrictive soils: does time from abandonment matter?
Authors: Martínez‐Duro E. , Ferrandis P. , Escudero A. , Luzuriaga A.L. , Herranz J.M.
Published: November 2009

Question: Our knowledge of secondary old‐field succession in Mediterranean environments is extremely poor and is non‐existent for restrictive soil conditions. How these ecosystems, such as those on semi‐arid gypsum outcrops, recover seems a priority for managing change and for ensuring conservation of specialized and endangered biota. We tested whether reinstallation of gypsum vegetation after cropland abandonment requires: (1) soil physical restructuring and (2) chemical readjustment to enable growth and survival of specialized gypsophilous vegetation, and more specifically how time from abandonment drives such environmental change.

Location: We sampled a complete set of old fields on gypsum soils (1–60 yr since abandonment) in Villarrubia de Santiago (Toledo, Spain).

Methods: Generalized linear models and model comparisons were used to analyse the effect of several environmental parameters on species abundance and richness. Ordination methods (canonical correspondence analyses and partial canonical correspondence analyses) were undertaken to evaluate compositional variation among the sampled fields.

Results: Secondary old‐field succession on semi‐arid Mediterranean gypsum soils was controlled by a complex set of factors acting relatively independently. Surprisingly, time since abandonment explains only a small proportion of compositional variation (3%). Conversely, soil chemical features independently from time since abandonment are important for explaining differences found in old‐field composition.

Conclusions: Secondary succession on specialized Mediterranean soils does not follow the widely described “amelioration” process in which soil features and composition are closely related over time. Restrictive soil conditions control both structure and functioning of mature communities and also secondary succession.
Landscape‐scale patterns of alien plant species on coastal dunes: the case of iceplant in central Italy
Authors: Carranza M. Laura , Carboni Marta , Feola Silverio , Acosta Alicia T. R.
Published: November 2009

Question: We investigated the spatial pattern of coastal landscapes invaded by iceplant (Carpobrotus aff. acinaciformis) focusing on two questions: (1) Does the spatial structure of iceplant patches differ from that of native natural costal dune cover types?; (2) Is the distribution of iceplant patches related to other cover types?

Location: Tyrrhenian coast of Central Italy.

Method: On the basis of a detailed land‐cover map, we calculated structural metrics for iceplant patches and for each native coastal dune cover category (mean patch size and patch shape index) and compared them by means of anova. To assess the spatial association between iceplant patches and the different cover types, we implemented an electivity analysis which analyses the frequency of common borders.

Results: The mapped coastal dune cover types included beaches, dunes and sand plain variants, related to the typical Tyrrhenian coastal dune vegetation zonation. Iceplant‐dominated vegetation presented elongated and irregularly shaped patches, which were not significantly different from most of the natural cover types suggesting a natural spread along the territory analysed. Iceplant patches were positively associated with beach, mobile and inter‐dune cover types indicating that these habitats are exposed to further alien spread. Iceplant patches were also positively associated with artificial surfaces highlighting this cover type as a possible source of propagule pressure.

Conclusions: The proposed landscape approach combining patch‐based metrics with edge‐based metrics provided a comprehensive description of the invaded coastal landscape. From an applied research perspective, this landscape approach could be useful in identifying the correct management strategies for alien‐invaded areas.
Human telomeric G‐quadruplex: thermodynamic and kinetic studies of telomeric quadruplex stability
Authors: Chaires Jonathan B.
Published: November 2009

Thermodynamic and kinetic studies complement high‐resolution structures of G‐quadruplexes. Such studies are essential for a thorough understanding of the mechanisms that govern quadruplex folding and conformational changes in quadruplexes. This perspective article reviews representative thermodynamic and kinetic studies of the folding of human telomeric quadruplex structures. Published thermodynamic data vary widely and are inconsistent; possible reasons for these inconsistencies are discussed. The key issue of whether such folding reactions are a simple two‐state process is examined. A tentative energy balance for the folding of telomeric quadruplexes in Na+ and K+ solution, and for the conformational transition between these forms is presented.
Calmodulin‐mediated regulation of the epidermal growth factor receptor
Authors: Sánchez‐González Pablo , Jellali Karim , Villalobo Antonio
Published: November 2009

In this review, we first describe the mechanisms by which the epidermal growth factor receptor generates a Ca2+signal and, subsequently, we compile the available experimental evidence regarding the role that the Ca2+/calmodulin complex, formed after the rise in cytosolic free Ca2+concentration, exerts on the receptor. We focus not only on the indirect action that Ca2+/calmodulin exerts on the epidermal growth factor receptor, as a result of the activation of distinct calmodulin‐dependent kinases, but also, and more extensively, on the direct interaction of Ca2+/calmodulin with the receptor. We also describe several mechanistic models that could account for the Ca2+/calmodulin‐mediated regulation of epidermal growth factor receptor activity. The control exerted by calmodulin on distinct epidermal growth factor receptor‐mediated cellular functions is also discussed. Finally, the phosphorylation of this Ca2+sensor by the epidermal growth factor receptor is highlighted.
Molecular basis of cytokine signalling – theme and variations
Authors: Sebald Walter , Nickel Joachim , Zhang Jin‐Li , Mueller Thomas D.
Published: November 2009

Cytokine receptors are crucial for the maintenance, regulation and growth of cells in multicellular organisms. As a common theme in cytokine signalling, single‐span receptor chains are assembled in the cell membrane by a ligand enabling cross‐activation of the aligned cytoplasmic receptor domains. Nature has created many variations of how this general principle is realized in a cell. Here we focus on cytokines of the four‐helix bundle (interleukins) and cystine knot (transforming growth factor‐β/bone morphogenetic proteins) families. Upon activation, receptor chains can form duos, trios, quartets and even larger assemblies. The structure of the extracellular ligand‐binding domain of a number of these receptor complexes has now been elucidated, providing the molecular basis for understanding the functional relevance of mechanistic diversity in a cellular context. Biochemical and structural data have revealed ligand recognition mechanisms. Contact sites are usually large and rather flat. A limited number of contact residues provide most of the binding free energy (hot spots). Leaks in hydrophobic seals appear to provide a mechanism for adjusting the affinity of a hot spot interaction (scalability). Bone morphogenetic protein ligands are often promiscuous and interact not only with receptors, but also with a multitude of modulator proteins, which inhibit or enhance bone morphogenetic protein signalling. Cytokine receptor systems offer promising targets for drug development. Information on the structure and the activation mechanism provides leads for developing biologicals, such as engineered cytokines, cytokine mutants acting as receptor antagonists and receptor extracellular ligand‐binding domain–Fc fusion proteins. Possible indications exist in the areas of haematology, immunology, inflammation, cancer and tissue regeneration.
Policy Attitudes, Ideological Values and Social Representations
Authors: Staerklé Christian
Published: November 2009

This article reviews research on policy attitudes and ideological values from the perspective of social representations theory. In the first part of the paper, key features of lay political thinking are presented, its pragmatic imperative, its focus on communication and the social functions of shared knowledge.Objectificationtransforms abstract and group‐neutral ideological values into concrete and socially useful knowledge, in particular stereotypes of value‐conforming and value‐violating groups. Such shared understandings of intergroup relations provide citizens with common reference knowledge which provides the cognitive and cultural basis of policy attitudes. Social representations theory further suggests that lay knowledge reflects the social context in which it has been elaborated (anchoring), an aspect which allows conceptualising aggregate‐level differences in policy attitudes. In the second part of the paper, a model of lay conceptions of social order is outlined which organises four shared conceptions of social order, along with the stereotype‐based thinking associated with each conception: Moral order, Free Market, Social diversity and Structural inequality. We conclude by arguing that policy attitudes are symbolic devices expressed to justify or to challenge existing social arrangements.
Quadrupole ICP‐MS: Introduction to Instrumentation, Measurement Techniques and Analytical Capabilities
Authors: Linge Kathryn L. , Jarvis Kym E.
Published: November 2009

The low detection limits and multi‐element capability of inductively coupled plasma‐mass spectrometry (ICP‐MS) makes it an attractive option in a wide range of environmental, medical, biological, industrial and archaeological applications. Quadrupole ICP‐MS is used to determine element concentrations in a diverse range of sample types, often very different from the geological applications for which ICP‐MS was originally developed. Whilst modern instruments are robust and capable of a high degree of automation, it is essential that users of both instrumentation and data are aware of the strengths and limitations of the technique. Many people who are now involved with the operation and application of ICP‐MS instruments are not specialists in the field, as was usually the case amongst early operators. This back‐to‐basics review is aimed at the novice user and includes a guide to ICP‐MS instrumentation and performance. Whilst solids, liquids and gases can all be measured by ICP‐MS, discussion of sample introduction is limited to liquids. Requirements for producing good quality data, including aspects of sample preparation, calibration, and methods of interference limitation are also discussed.
Assessment of referral patterns for CT KUB in a tertiary setting
Authors: Jo H , Buckley BT
Published: November 2009

The purpose of this study was to assess the referral patterns and the use of unenhanced renal tract CT (CT KUB) for investigating patients presenting with clinically suspected renal colic. We retrospectively reviewed 500 consecutive CT KUB studies requested for suspected renal colic carried out at a single institution between December 2006 and July 2007. Follow‐up radiology reports and discharge summaries on the hospital clinical Intranet were also reviewed. Studies were analysed for characteristics including patient demographics, referring clinical team, time of referral, final diagnosis and requirement for further imaging. The majority of requests were from Emergency (ED) or Urology Departments (49%, 245 out of 500, and 37%, 186 out of 500, respectively). The positive rate for urolithiasis was 67% (337 out of 500), the negative rate was 25% (123 out of 500), and 8% (40 out of 500) of patients had alternative significant findings. Female patients were more likely to have a negative study than male patients (35 versus 20%, P < 0.0001) and more likely to have alternative significant pathology (12 versus 6%, P < 0.0001). Patients referred by specialities other than Urology and ED were more likely to be female and have a negative or alternative finding (P < 0.0001). CT KUB is a widely used first method of investigation for patients with suspected renal colic with a high positive predictive value allowing rapid diagnosis and intervention. However, given the high rate of negative or alternative findings on CT KUB in young women, especially those referred by specialities other than ED or Urology, ultrasound should be considered as an alternative imaging method to minimise unnecessary radiation exposure.
Use of deodorants during adjuvant breast radiotherapy: A survey of compliance with standard advice, impact on patients and a literature review on safety
Authors: Graham PH , Graham JL
Published: November 2009

Proscription of antiperspirant or deodorant use during adjuvant breast radiotherapy is common. The investigators were seeking an information base to facilitate design of an appropriate controlled trial of the use of deodorants during radiotherapy.

The first component consisted of a survey of women after adjuvant breast radiotherapy seeking information about routine deodorant use and potential concern if deodorants were not permitted during radiotherapy. The second component comprised a literature search for any existing controlled evidence regarding harm from deodorant use during radiotherapy.

Four hundred fourteen women completed surveys. Two hundred eighty recalled advice against deodorants. Two hundred ninety‐nine women routinely used deodorants, 70% of whom used roll‐on products. Forty‐five continued deodorant use during radiation, 20 of these despite recalling advice not to wear a deodorant. Of the 233 women who routinely wore a deodorant but abstained during radiotherapy, 19% expressed a lot of concern about body odour and 45% were slightly concerned. Three controlled studies totalling 310 patients report specific deodorants versus no deodorant use which did not show statistically significantly increased skin reactions, but had only a small subset with axillary irradiation.

The proscription of deodorant use during radiotherapy is of unproven benefit and causes body odour concern to the majority of women who are usual deodorant users. The next most appropriate trial would compare use of the usual deodorant versus no deodorant, would encompass a significant number of women with radiotherapy to the axilla or application of deodorant to irradiated skin areas, and include endpoints other than skin reaction alone.
Prospective development of an individualised predictive model for treatment coverage using offline cone beam computed tomography surrogate measures in post‐prostatectomy radiotherapy
Authors: Tran PK , Haworth A , Foroudi F , Paneghel A , Herschtal AG , Tai KH , Williams SG , Soteriou S , Laferlita M , Duchesne GM
Published: November 2009

The aim of this study is to prospectively evaluate and model surrogate explanatory variables (SEVs) of target coverage and rectal dose pertaining to soft tissue anatomy visualised on cone beam computed tomography (CBCT) for incorporation into post‐prostatectomy treatment coverage verification protocols. Twenty post‐prostatectomy patients treated with conformal prostate bed radiotherapy (64–74 Gy) underwent CBCT daily at fractions 1 to 5, and then weekly. Treatment coverage was defined on each CBCT using ‘PTV95’, percentage of the CBCT PTV covered by original treatment fields, and ‘RECTD50’, dose delivered to 50% of CBCT rectal volume by original treatment fields. Three candidate SEVs for treatment coverage were defined for each scan: anterior rectal wall movement, change in bladder length and bladder base movement. Both anterior rectal wall movement and increase in bladder length predicted for the decreased PTV95 (P < 0.001 for each). Anterior movement of the anterior rectal wall predicted for increased RECTD50 (P < 0.001). Predictive models for the PTV95 and RECTD50 that accept the significant SEVs as inputs were developed. We developed simple CBCT‐acquired soft tissue anatomic surrogate measures that signal changes in target coverage and rectal dose during post‐prostatectomy radiotherapy. Conventional bony anatomy patient position verification protocols were inadequate in accounting for soft tissue target and organ variation seen with CBCT.
Variation in human performance in the hypoxic mountain environment
Authors: Martin Daniel S. , Levett Denny Z. H. , Grocott Mike P. W. , Montgomery Hugh E.
Published: November 2009

Ascent to altitude is associated with a fall in barometric pressure, and with it a decline in the partial pressure of atmospheric (and thus alveolar) oxygen. As a result, a variety of adaptive physiological processes are engaged to mitigate the fall in tissue convective oxygen delivery which might otherwise occur. The magnitude and nature of such changes is also modified with time, a process known as acclimatization. However, other phenomena are at work; the ability to perform physical work at altitude falls in a manner which is not wholly related to changes in arterial oxygen content. Indeed, alterations in local skeletal muscle blood flow and metabolism may play an axial role. Thus, for those who are not native to high altitude, the ability to compete at altitude is likely to be impaired. The magnitude of such impairment in performance, however, differs greatly between individuals, and it seems that genetic variation underpins much of this difference. The identification of the relevant genetic elements is in its infancy in humans, but ongoing work is likely to help us gain an increasing understanding of how humans adapt to altitude and to develop mitigating interventions.