bluuebunny/crossref_metadata_2025 huggingface dataset:
Stochastic analysis of nonlinear biodegradation in regimes controlled by both chromatographic and dispersive mixing
Authors: Janssen Gijs M. C. M. , Cirpka Olaf A. , van der Zee Sjoerd E. A. T. M.
Published: January 2006

Nonlinear biodegradation in natural porous media is affected by the heterogeneity of the formation and dispersive mixing processes. We analyze these coupled effects by combining recent advances in analytical one‐dimensional modeling of bioreactive transport with stochastic concepts of dispersive mixing in heterogeneous domains. Specifically, we model bioremediation of a sorbing contaminant undergoing nonlinear biodegradation in heterogeneous aquifers applying the stochastic‐convective and the advective‐dispersive stream tube approaches, in which we use a semianalytical traveling wave solution for one‐dimensional reactive transport. The results of numerical simulations agree excellently with both models, which establishes that the traveling wave solution is an efficient and accurate way to evaluate the development of intrastream tube concentration distributions and that the advective‐dispersive stream tube approach is suitable to describe nonlinear bioreactive transport in systems controlled by local‐scale dispersion. In contrast with conservative transport the mean contaminant flux is shown to be significantly influenced by transverse dispersion, even for realistic Peclet values. Furthermore, asymptotic front shapes are shown to be neither Fickian nor constant (traveling wave behavior), which raises questions about the current practice of upscaling bioreactive transport. The error caused by neglecting local dispersion was found to increase with time and to remain significant even for large retardation differences between electron acceptor and contaminant. This implies that, even if reaction rates are dominated by chromatographic mixing, the dispersive mixing process cannot be disregarded when predicting bioreactive transport.
Granzyme A, which causes single‐stranded DNA damage, targets the double‐strand break repair protein Ku70
Authors: Zhu Pengcheng , Zhang Dong , Chowdhury Dipanjan , Martinvalet Denis , Keefe Dennis , Shi Lianfa , Lieberman Judy
Published: January 2006

Granzyme A (GzmA) induces caspase‐independent cell death with morphological features of apoptosis. Here, we show that GzmA at nanomolar concentrations cleaves Ku70, a key double‐strand break repair (DSBR) protein, in target cells. Ku70 is cut after Arg301, disrupting Ku complex binding to DNA. Cleaving Ku70 facilitates GzmA‐mediated cell death, as silencing Ku70 by RNA interference increases DNA damage and cell death by GzmB cluster‐deficient cytotoxic T lymphocytes or by GzmA and perforin, whereas Ku70 overexpression has the opposite effect. Ku70 has two known antiapoptotic effects—facilitating DSBR and sequestering bax to prevent its translocation to mitochondria. However, GzmA triggers single‐stranded, not double‐stranded, DNA damage, and GzmA‐induced cell death does not involve bax. Therefore, Ku70 has other antiapoptotic functions in GzmA‐induced cell death, which are blocked when GzmA proteolyses Ku70.
Adenomatous polyposis coli‐deficient zebrafish are susceptible to digestive tract neoplasia
Authors: Haramis Anna‐Pavlina G , Hurlstone Adam , van der Velden Yme , Begthel Harry , van den Born Maaike , Offerhaus G Johan A , Clevers Hans C
Published: January 2006

Truncation of the tumour suppressor adenomatous polyposis coli (APC) constitutively activates the Wnt/β‐catenin signalling pathway. This event constitutes the primary transforming event in sporadic colorectal cancer in humans. Moreover, humans or mice carrying germline truncating mutations in APC develop large numbers of intestinal adenomas. Here, we report that zebrafish that are heterozygous for a truncating APC mutation spontaneously develop intestinal, hepatic and pancreatic neoplasias that are highly proliferative, accumulate β‐catenin and express Wnt target genes. Treatment with the chemical carcinogen 7,12‐dimethylbenz[a]anthracene accelerates the induction of these lesions. These observations establish apc‐mutant zebrafish as a bona fide model for the study of digestive tract cancer.
Socio–instrumental Usability: IT is all about Social Action1
Authors: Ågerfalk Pär J , Eriksson Owen
Published: January 2006

Usability is an important concept that seems to receive less attention than it deserves outside of the core Human–Computer Interaction community. The reason for this apparent lack of interest may stem from an overly instrumental orientation towards usability that does not appeal to more socially oriented researchers. Three central criteria for usability, as reflected in the contemporary literature, are the effectiveness, efficiency and satisfaction with which users can achieve specified goals. These criteria are often expressed in terms of achieving goals, which, at least tacitly, seem to be restricted to goals related to an instrumental view on the use of IT. To broaden this view, the paper elaborates on how the concept of usability can be understood and used within a social action context. How social goals are related to the effectiveness, efficiency and satisfaction criteria is addressed specifically. It is argued that in order truly to understand usability, we must consider both instrumental and social goals since their combination constitute a fundamental part of the social action context in which systems are used. Both instrumental and social goals affect the way systems and use-situations are designed and conceived. Interpreting usability from this broad social action perspective may be a way to make the concept more accepted throughout the wide variety of areas dealing with the design of IT systems.
A Review of the Predictors, Linkages, and Biases in IT Innovation Adoption Research
Authors: Jeyaraj Anand , Rottman Joseph W , Lacity Mary C
Published: January 2006

We present a review and analysis of the rich body of research on the adoption and diffusion of IT-based innovations by individuals and organizations. Our review analyzes 48 empirical studies on individual and 51 studies on organizational IT adoption published between 1992 and 2003. In total, the sample contains 135 independent variables, eight dependent variables, and 505 relationships between independent and dependent variables. Furthermore, our sample includes both quantitative and qualitative studies. We were able to include qualitative studies because of a unique coding scheme, which can easily be replicated in other reviews. We use this sample to assess predictors, linkages, and biases in individual and organizational IT adoption research. The best predictors of individual IT adoption include Perceived Usefulness, Top Management Support, Computer Experience, Behavioral Intention, and User Support. The best predictors of IT adoption by organizations were Top Management Support, External Pressure, Professionalism of the IS Unit, and External Information Sources. At the level of independent variables, Top Management Support stands as the main linkage between individual and organizational IT adoption. But at an aggregate level, two collections of independent variables were good predictors of both individual and organizational IT adoption. These were innovation characteristics and organizational characteristics. Thus, we can consistently say that generic characteristics of the innovation and characteristics of the organization are strong predictors of IT adoption by both individuals and organizations. Based on an assessment of the predictors, linkages, and known biases, we prescribe 10 areas for further exploration.
Applying Multiple Perspectives to the BPO decision: A Case Study of Call Centres in Australia
Authors: Borman Mark
Published: January 2006

Information Technology enabled Business Process Outsourcing (BPO) is a growing phenomenon, yet little research has been conducted to understand the factors that determine its appropriateness for organisations and what capabilities they should seek in potential suppliers. A multi-perspective approach to the BPO decision, encompassing the transaction, the organisation and its context, is proposed and a set of supplier capabilities to deliver upon it is outlined. A case study of outsourced call centres in Australia, based upon interviews with three suppliers and three clients, suggests such a multi-perspective approach is useful but that the interaction between the factors shaping the BPO decision is more complex than envisaged. The case also suggests that a common set of capabilities is sought from suppliers – though it is narrower than first proposed.
Accurate ab initio predictions of ionization energies and heats of formation for the 2-propyl, phenyl, and benzyl radicals
Authors: Lau K.-C. , Ng C. Y.
Published: January 2006

The ionization energies (IEs) for the 2-propyl (2-C3H7), phenyl (C6H5), and benzyl (C6H5CH2) radicals have been calculated by the wave-function-based ab initio CCSD(T)/CBS approach, which involves the approximation to the complete basis set (CBS) limit at the coupled cluster level with single and double excitations plus quasiperturbative triple excitation [CCSD(T)]. The zero-point vibrational energy correction, the core-valence electronic correction, and the scalar relativistic effect correction have been also made in these calculations. Although a precise IE value for the 2-C3H7 radical has not been directly determined before due to the poor Franck-Condon factor for the photoionization transition at the ionization threshold, the experimental value deduced indirectly using other known energetic data is found to be in good accord with the present CCSD(T)/CBS prediction. The comparison between the predicted value through the focal-point analysis and the highly precise experimental value for the IE(C6H5CH2) determined in the previous pulsed field ionization photoelectron (PFI-PE) study shows that the CCSD(T)/CBS method is capable of providing an accurate IE prediction for C6H5CH2, achieving an error limit of 35 meV. The benchmarking of the CCSD(T)/CBS IE(C6H5CH2) prediction suggests that the CCSD(T)/CBS IE(C6H5) prediction obtained here has a similar accuracy of 35 meV. Taking into account this error limit for the CCSD(T)/CBS prediction and the experimental uncertainty, the CCSD(T)/CBS IE(C6H5) value is also consistent with the IE(C6H5) reported in the previous HeI photoelectron measurement. Furthermore, the present study provides support for the conclusion that the CCSD(T)/CBS approach with high-level energy corrections can be used to provide reliable IE predictions for C3–C7 hydrocarbon radicals with an uncertainty of ±35meV. Employing the atomization scheme, we have also computed the 0 K (298 K) heats of formation in kJ∕mol at the CCSD(T)/CBS level for 2-C3H7∕2-C3H7+,C6H5∕C6H5+, and C6H5CH2∕C6H5CH2+ to be 105.2∕822.7(90.0∕806.4),351.4∕1148.5(340.4∕1138.8), and 226.2∕929.0(210.3∕912.7), respectively. Comparing these values with the available experimental values, we find that the discrepancies for the 0 and 298 K heats of formation values are ⩽2.6kJ∕mol for 2-C3H7∕2-C3H7+,⩽4.1kJ∕mol for C6H5∕C6H5+, and ⩽3.2kJ∕mol for C6H5CH2∕C6H5CH2+.
Following peak profiles during elastic and plastic deformation: A synchrotron-based technique
Authors: Van Swygenhoven H. , Schmitt B. , Derlet P. M. , Van Petegem S. , Cervellino A. , Budrovic Z. , Brandstetter S. , Bollhalder A. , Schild M.
Published: January 2006

Understanding the elastic and plastic deformation properties of nanostructured metals requires the development of in situ testing methods that can follow the footprints of the deformation mechanism(s) during mechanical testing. Here we present an in situ synchrotron x-ray-diffraction technique which allows the measurement of diffraction profiles continuously during mechanical testing, providing an in situ peak profile analysis capability. The in situ approach is achieved thanks to the development of a microstrip detector allowing the instantaneous measurement of the diffraction pattern over a 2θ range of 60°. This in situ technique allows for the first time a comparison of the footprints of the plastic deformation mechanism during loading and after unloading. The measurements are performed on several types of freestanding dog bones, covering sample thicknesses down to the submicron range.
A (4×2) reconstruction of CuInSe2 (001) studied by low-energy electron diffraction and soft x-ray photoemission spectroscopy
Authors: Deniozou Th. , Esser N. , Schulmeyer Th. , Hunger R.
Published: January 2006

Clean and flat (001) surfaces of CuInSe2∕GaAs grown by molecular-beam epitaxy could be prepared by the combination of a Se capping and decapping process and subsequent Ar+ ion sputtering and annealing. The formation of a (4×2) reconstruction was observed with low-energy electron diffraction. Soft x-ray photoemission spectroscopy was performed on the prepared surfaces and revealed surface core-level binding energy shifts in the Cu2p3∕2, Se3d, and In4d levels which are associated with surface atoms. The structure model of a combined metal adatom-Se dimer structure is proposed to refer to the (4×2) reconstruction.
Initiation techniques and the vacuum-ultraviolet-radiation efficiency of a stabilized multichannel surface discharge
Authors: Tcheremiskine V. I. , Uteza O. P. , Sentis M. L. , Mikheev L. D.
Published: January 2006

Multichannel surface discharges possess a number of advantageous characteristics for the optical pumping of photochemically driven lasers. This work reports on a type of large-area low-inductance sources of intense UV-VUV (vacuum-ultraviolet) radiation based on spatially stabilized multichannel discharges in gases. The discharges consist of several dozens of closely located parallel plasma channels initiated synchronously along a dielectric surface on the area of several hundred square centimeters. In comparison with a large-area diffuse surface discharge, the plasma confinement within relatively thin channels greatly improves the efficiency of the discharge emission in the VUV spectral range. Several techniques are introduced, which allow a synchronous formation and homogeneous development of multiple spatially stabilized discharge channels. Technical efficiency of the discharge radiation within the spectral range of 120–200nm reaches 5% and an effective brightness temperature of the radiating plasma exceeds 20kK. Synchronous operation of a number of multichannel discharge modules producing high-intensity submicrosecond optical pulses is demonstrated, which is of importance for the pump source scaling and geometrical adaptation.
Calibrating bead displacements in optical tweezers using acousto-optic deflectors
Authors: Vermeulen Karen C. , van Mameren Joost , Stienen Ger J. M. , Peterman Erwin J. G. , Wuite Gijs J. L. , Schmidt Christoph F.
Published: January 2006

Displacements of optically trapped particles are often recorded using back-focal-plane interferometry. In order to calibrate the detector signals to displacements of the trapped object, several approaches are available. One often relies either on scanning a fixed bead across the waist of the laser beam or on analyzing the power spectrum of movements of the trapped bead. Here, we introduce an alternative method to perform this calibration. The method consists of very rapidly scanning the laser beam across the solvent-immersed, trapped bead using acousto-optic deflectors while recording the detector signals. It does not require any knowledge of solvent viscosity and bead diameter, and works in all types of samples, viscous or viscoelastic. Moreover, it is performed with the same bead as that used in the actual experiment. This represents marked advantages over established methods.
Development of high temporally and spatially (three-dimensional) resolved formaldehyde measurements in combustion environments
Authors: Olofsson J. , Richter M. , Aldén M. , Augé M.
Published: January 2006

In the present article a multi-YAG laser cluster and a framing camera have been applied for ultrahigh framing rate and three-dimensional measurements of formaldehyde distribution in flames and engines. The measurement technique utilizes a laser/detection system which has been adopted for the generation of eight laser pulses at 355 nm. By combining these lasers with a framing camera, short movies showing the formaldehyde distributions in combustion phenomena can be recorded, by means of planar laser-induced fluorescence. The technique is successfully demonstrated in a laboratory flame as well as in an engine. In addition to the temporally resolved experiments also three-dimensional measurements are performed by sweeping the eight generated laser sheets across the flame by the use of a fast scanning mirror. By proper triggering of the laser sweep and the detector a three-dimensional image showing the formaldehyde distribution in the flame can be created, which is also demonstrated.
Determination of critical thickness of ZnS∕GaP epilayers using spectroscopic ellipsometry
Authors: Kim D.-J. , Yu Y.-M. , Choi Y. D. , Lee J.-W. , Kim C.-S.
Published: January 2006

High-quality ZnS∕GaP (100) epilayers were grown by hot-wall epitaxy, and their optical properties were investigated in a wide photon-energy range between 3.0 and 8.5 eV at room temperature using spectroscopic ellipsometry. The obtained data were analyzed for the critical points of pseudodielectric function spectra, ⟨ε(E)⟩=⟨ε1(E)⟩+i⟨ε2(E)⟩, such as E0,E0+Δ0,E1, and three E2(Σ,Δ,Γ) structures. In particular, it was found that the E1 structure was separated into an E1(Λ3→Λ1) structure and an E1′(L3→L1) structure by the strong strain effect in thinner ZnS epilayers. This E1′ structure was observed by ellipsometric measurements. The position of the E1′ peak was varied with a thickness change of the epilayers. Note that the critical thickness determined by the change of E1′ peak was compared with the result obtained by the full width at half maximum of the double crystal rocking curve, and good agreement was obtained.
Manipulation of g-factor in diluted magnetic semiconductors quantum dots: Optical switching control
Authors: López-Richard V. , Prado S. J. , Marques G. E. , Trallero-Giner C. , Alcalde A. M.
Published: January 2006

We propose an optical switch based on a spin tuning mechanism in diluted-magnetic semiconductor quantum dots. At certain critical magnetic field, Bc, the Zeeman spin-splitting energies can cross leading to a zero value of the effective electron g-factor and the Fermi level undergoes a spin-flip transition. Magneto-optical switching is obtained for magnetic fields below and above Bc. Correlations between Bc, confinement shapes, dot sizes, and host material compositions have been established within well-defined temperature and magnetic impurity composition ranges. The generality of the presented theoretical framework allows for its application to magnetic field controlled quantum dot arrays, and spin-injection among others.
GaN quantum dots doped with Tb
Authors: Hori Y. , Andreev T. , Jalabert D. , Monroy E. , Dang Le Si , Daudin B. , Tanaka M. , Oda O.
Published: January 2006

Tb-doped GaN quantum dots grown by molecular beam epitaxy have been studied. These nanostructures present intense photoluminescence from intra-4f transitions of Tb3+ ions. It has been found that Tb atoms enhance the desorption process of Ga adatoms from the growing surface, leading to a reduction of the growth rate and, eventually, to an inhibition of the GaN quantum dot formation for a Tb content of about 2% at the growth temperature of 760°C. The presence of Tb inside quantum dots is suggested by intense photoluminescence in the green spectral range at room temperature from intra-4f transitions of Tb3+ ions, by contrast to the Tb-doped GaN thick layers.
Effects of substrate curvature on the adsorption of poly(3-hexylthiophene) on single-walled carbon nanotubes
Authors: Goh Roland G. S. , Motta Nunzio , Bell John M. , Waclawik Eric R.
Published: January 2006

A detailed study of poly(alkylthiophene) self-assembly and organization on single-walled carbon nanotubes (SWNTs) is presented. Monolayers of regioregular poly(3-hexyl thiophene) (rrP3HT) adsorbed on SWNTs have been imaged by using scanning tunneling microscopy. Our results show that the rrP3HT interchain distance is greater for rrP3HT monolayers adsorbed onto the curved surfaces of SWNTs than on the flat surfaces of highly ordered pyrolytic graphite samples. Comparisons between the native polymer deposited on graphite and the composite structure confirmed that the presence of carbon nanotubes in rrP3HT produces a new material with a high degree of order at the molecular level.
In situ synthesis and nonlinear optical properties of Au:Ag nanocomposite polymer films
Authors: Karthikeyan B. , Anija M. , Philip Reji
Published: January 2006

We report a simple in situ synthesis procedure for Au:Ag nanocomposite polymer (NCP) films using polyvinyl alcohol as the reducing agent. Optical measurements show absorption bands of varying strengths around 530 and 410 nm. The presence of nanoparticles is confirmed from Transmission Electron Microscopy (TEM). Nonlinear optical response is studied using 7 ns laser pulses, for near-resonant and off-resonant excitation wavelengths (532 and 1064 nm, respectively). Samples exhibit saturable as well as induced absorption. These materials have the potential to be used as saturable absorbers and optical limiters.
Reduction of threading dislocation densities in AlN∕sapphire epilayers driven by growth mode modification
Authors: Bai J. , Dudley M. , Sun W. H. , Wang H. M. , Khan M. Asif
Published: January 2006

A strategy to reduce the density of threading dislocations (TDs) in AlN epilayers grown on sapphire substrates is reported. The TDs experience a redirection of their line orientation which is found to coincide with imposed increases in both of V/III ratio and overall flux rate leading to the formation of an internal subinterface delineated by the changes in dislocation orientation. Threading dislocations either experience large kinks and then redirect into threading orientation or form dipole half loops via annihilation of redirected threading segments of opposite sign with the latter leading to a significant dislocation density reduction. These phenomena can be accounted for by a transition of growth mode from atomic step flow to two-dimensional layer-by-layer growth which accompanies the imposed changes in V/III ratio and flux. As this occurs, macrosteps (several atomic layers thick) laterally overgrow pre-existing dislocation outcrops. Image forces initiate the redirection processes and create trailing segments parallel to the interface between the advancing macrostep and the surface outcrop. This horizontal segment can be forced to redirect into threading orientation should another macrostep traveling in the opposite direction be encountered. Image forces again nucleate the redirected segment which is then replicated as the crystal grows. A dipole half loop will form if two dislocations with opposite sign are redirected so as to meet each other.
Pore size dependence of field emission from nanoscale porous carbon
Authors: Ojima M. , Hiwatashi S. , Araki H. , Fujii A. , Ozaki M. , Yoshino K.
Published: January 2006

Carbon inverse opals with three-dimensional nanoporous structures are fabricated by a template method using synthetic opals formed by the sedimentation of SiO2 spheres. The pore size of the carbon inverse opals ranges widely from about 74 nm to 550 nm depending on the diameter of the SiO2 spheres. These nanoporous structures of carbon exhibit excellent characteristics as electron emitters. As the pore size of porous carbon decreases, the effective emission area of field emission increases. The main emitter sites of porous carbon are interpreted to be the edges formed in the boundary of the neighboring pores. The emission characteristics have drastically improved upon heat treatment at high temperatures (about 2760 °C).
Making Something of Nothing: The Excesses of Storytelling in the
Lais
of Marie de France and
La Chastelaine de Vergi
Authors: Ramm Ben
Published: January 2006

The notion of exemplarity in literary texts is beset by irony and paradox, for the example must serve the dual and contrary functions of being both a one-off and also a paradigm to be copied. This article seeks to explore ways in which a ‘tactic of exemplarity’ at work in the text seizes upon the inherent ambiguity of the example in order to question the purpose and indeed the very viability of an exemplary narrative. The discussion focuses on two Old French texts which share common narrative material and employ this ‘tactic of exemplarity’: the twelfth-century Anglo-Norman
Lais
, attributed to Marie de France, and the anonymous thirteenth-century poem
La Chastelaine de Vergi
. Through analysis of the texts' narrative framework—their prologues and/or epilogues—it is argued that a fundamental disparity emerges between the proclaimed didacticism of the narrative example and the way in which that example is then (not) worked through the text. The example is constituted by these texts as an absence or narrative hiatus, suggesting that the example represents a fundamental aporia in the text, and that any claim to exemplarity necessarily implies a problematic narrative standpoint which leaves itself open to deconstruction.
The Meaning Beyond the Dress: Alterity and Economy of Desire in Mallarmé's
Berthe Morisot
Authors: Anderson Jill
Published: January 2006

This essay explores Mallarmé's late prose text
Berthe Morisot
,

1

the preface to the catalogue of the 1896 posthumous exhibition. Morisot was one of Mallarmé's privileged others. Their relationship sheds light on the economy of desire and evolving cultural practice in two major figures of late nineteenth-century France. I aim to show how poet and painter came to speak the same language via a remarkable intercultural and gender exchange. The narrator's relational self hides behind the dispassionate art historian's mask, yet emerges in unexpected ways.

This elegiac text stages an eroticized encounter with a feminine alter ego that takes on broader significance, a ‘symptom’ of the foreign that disrupts and enriches French culture. Speaking as an outsider, yet clearly implicated, Mallarmé's narrator moves from the intimate to public sphere and from the foreign to the national. The poet recovers a marginalized, private form of discourse, previously eschewed, to forge
une poésie à côté de la loi
such as Kahn had wished, revealing the passionate attachment to the other generally erased for ideological reasons. Ostensibly evacuated from Mallarmé's poetic practice as fitting only for autobiography,
le sentiment
, purified according to Morisot's definition, is conveyed in a language of restrained sensuality.
Neogene supradetachment basin development on Crete (Greece) during exhumation of the South Aegean core complex
Authors: van Hinsbergen Douwe J. J. , Meulenkamp Johan E.
Published: January 2006

Tertiary extension in the Aegean region has led to extensional detachment faulting, along which metamorphic core complexes were exhumed, among which is the Early to Middle Miocene South Aegean core complex. This paper focuses on the supradetachment basin developed during the final stages of exhumation of the South Aegean core complex along the Cretan detachment, plus the Late Miocene to Pliocene basin development and palaeogeography associated with the southward motion of Crete during the opening of the Aegean arc. For the latter purpose, the sedimentary and palaeobathymetric evolutions of a large number of Middle Miocene to Late Pliocene sequences exposed on Crete, Gavdos and Koufonisi were studied. The supradetachment basin development of Crete is characterised by a break‐up of the hanging wall of the Cretan detachment into extensional klippen and subsequent migration of laterally coexisting sedimentary systems, and finally the deformation of the exhumed core complex by processes related to the opening of the Aegean arc. Hence, three main tectonic phases are recognised: (1) Early to Middle Miocene N–S extension formed during the Cretan detachment, exhumed in the South Aegean core complex. The Cretan detachment remained active until 11–10 Ma, based on the oldest sediments that unconformably overlie the metamorphic rocks. Successions older than 11–10 Ma unconformably overlie only the hanging wall of the Cretan detachment, and do not contain fragments of the footwall rocks; they therefore predate the oldest exposure of the metamorphic rocks of the footwall. The hanging wall rocks and Middle Miocene sediments form isolated blocks on top of the exhumed metamorphic rocks, which are interpreted as extensional klippen. (2) From approximately 10 Ma onward, southward migration of the area that presently covers Crete was accompanied by E–W extension, and the opening of the Sea of Crete to the north. Contemporaneously, large folds with WNW–ESE striking, NNE dipping axial planes developed, possibly in response to sinistral transpression. (3) During the Pliocene, Crete emerged and tilted to the NNW, probably as a result of left‐lateral transpression in the Hellenic fore‐arc, induced by the collision with the African promontory.
Side‐effects of allergen‐specific immunotherapy. A prospective multi‐centre study
Authors: Winther L. , Arnved J. , Malling H.‐J. , Nolte H. , Mosbech H.
Published: January 2006

Background and objective
The safety of allergen‐specific immunotherapy (SIT) is a parameter of great interest in the overall assessment of the treatment. A clinical database was developed in order to obtain early warnings of changes in the frequency and severity of side‐effects and sufficient data for the evaluation of possible risk factors.

Methods
During a 3‐year period, four allergy centres in Copenhagen, Denmark, included data from all patients initiating SIT to a common database. Information on initial allergic symptoms, allergens used for treatment, treatment regimens and systemic side‐effects (SSEs) during the build‐up phase was collected.

Results
A total of 1038 patients received treatment with 1709 allergens (timothy, birch, mugwort, house dust mite (HDM), cat, and wasp and bee venom), 23 047 injections in total. Most SIT patients completed the updosing phase without side‐effects, but there was a significant difference between allergens: wasp (89%), birch (82%), HDM (81%), cat (74%) and grass (70%) (P=0.004). A total of 582 SSEs were registered in 341 patients. Most side‐effects were mild grade 2 reactions (78%). A difference in severity between allergens was observed (P=0.02), with grass giving most problems. The type of allergen but not patient‐ or centre‐related parameters seemed predictive of side‐effects.

Conclusions
Allergen extracts differ in their tendency to produce side‐effects. Multi‐centre studies like the present one allow more patients to be evaluated, and thereby provide a more efficient surveillance of side‐effects. Online Internet‐based registration to a central national database of every allergen injection would be an even more powerful tool for evaluation of risk factors and surveillance of side‐effects.
Repair of the injury to respiratory epithelial cells characteristic of asthma is stimulated byAllomyrina dichotomaagglutinin specific serum glycoproteins
Authors: Patchell B. J. , Dorscheid D. R.
Published: January 2006

BackgroundThe airway epithelium acts as a protective barrier, separating the external environment from the underlying tissue. Daily challenges result in damage to the epithelium that, in normal individuals, is quickly and effectively repaired. In respiratory diseases, such as asthma, this repair is compromised. Following injury to the epithelium, plasma leaks into the airway lumen acting as a protective protein cap. Carbohydrates are mediators of epithelial repair, however, the associated regulatory proteins remain unknown.

ObjectiveTo identify mediators of epithelial repair based on their carbohydrate moieties using anin vitrowound repair culture model of human airway epithelial cells (1HAEo−).

MethodsUsing the lectinAllomyrina dichotomaagglutinin (AlloA) as a tool, ligands essential in the repair of damaged epithelium were characterized. AlloA was subsequently used to purify and identify a glycoprotein associated with epithelial repair.

ResultsThe addition of AlloA to the media of mechanically wounded monolayers inhibited repair. Fetuin, a highly glycosylated serum protein, was identified as a glycoprotein bound by AlloA. The addition of fetuin to serum starved monolayers stimulated wound closure.

ConclusionThese results indicate that following mechanical injury to the epithelium, serum glycoproteins, not only provide a protective barrier, but also are involved in the initiation of wound closure.
A hydrolysed rice‐based formula is tolerated by children with cow's milk allergy: a multi‐centre study
Authors: Fiocchi A. , Restani P. , Bernardini R. , Lucarelli S. , Lombardi G. , Magazzù G. , Marseglia G. L. , Pittschieler K. , Tripodi S. , Troncone R. , Ranzini C.
Published: January 2006

Background
Children allergic to cow's milk are fed a soy‐ or a hydrolysed cow's milk‐based substitute. Neither can rule out a sensitization risk. Previous studies have shown that hydrolysed rice is tolerated by animals and children with multiple food hypersensitivities.

Objective
A prospective clinical assessment of tolerance to a rice‐based hydrolysed formula was carried out in children allergic to cow's milk.

Patients and methods
One hundred children (42 girls and 58 boys, mean age 3.17±2.93 years, median 2.20, range 0.18–14.6 years) with a history of immediate reactions to cow's milk and confirmed at double‐blind, placebo‐controlled food challenge (DBPCFC) when not contraindicated were assessed for clinical tolerance to cow's milk proteins. Their allergy work‐up included skin prick tests with whole milk, α‐lactalbumin (ALA), β‐lactoglobulin (BLG) and total caseins, and specific IgE determinations using CAP technology were performed against whole milk, ALA, BLG and casein. Sensitization to rice and rice‐based hydrolysed formula was similarly investigated. Patients' sera were evaluated at immunoblotting for specific IgE to cow's milk proteins, rice and rice‐based hydrolysed formula. DBPCFC was carried out with increasing doses of a rice‐based hydrolysed formula.

Results
All patients were sensitized to cow's milk and/or at least one cow's milk protein fraction. Eighty‐seven out of 99 were positive to cow's milk and/or a cow's milk protein fraction at skin prick test. Positive (>0.35 kUA/L) specific IgE determinations were found for cow's milk and/or milk fractions (92/95), rice (21/91) and hydrolysed rice infant formula (4/91). At immunoblotting, sera from 96 children were positive to α‐casein (n=54), β‐casein (n=38), ALA (n=57), BLG (n=37) and bovine serum albumin (n=61). Similarly, although patients' sera often contained specific IgE against rice proteins at CAP (21/91) and immunoblotting (70/96), only six very weakly positive responses were observed against rice‐based hydrolysed formula. All DBPCFC with rice‐based hydrolysed formula were negative.

Conclusions
Rice‐based hydrolysed formula is a possible alternative not only for children with multiple allergies, but also for children with cow's milk allergy.
Tumour necrosis factor-α production stimulated by heat shock protein 70 and its inhibition in circulating dendritic cells and cells eluted from mucosal tissues in Crohn’s disease
Authors: Whittall T , Wang Y , Kelly C G , Thompson R , Sanderson J , Lomer M , Soon S Y , Bergmeier L A , Singh M , Lehner T
Published: January 2006

The objectives were to study the effect of microbial 70 kDa heat shock protein (HSP70) on the production of tumour necrosis factor (TNF)-α and interleukin (IL)-12 by dendritic cells (DC) from patients with Crohn’s disease. TNF-α concentration was increased significantly when DC from Crohn’s disease were stimulated with HSP70 or CD40L and this was associated with signalling by the extracellular signal regulated kinase (ERK) 1/2 and p38 mitogen activated protein (MAP) kinase pathway. IL-12 production was also increased when DC were stimulated with HSP70. Cells eluted from inflamed intestinal mucosa from Crohn’s disease, stimulated with HSP70, CD40L or lipopolysaccharide produced significantly greater TNF-α and IL-12 concentrations than cells from uninflamed mucosa. Significant inhibition of TNF-α production was demonstrated when DC from peripheral blood mononuclear cells or cells eluted from intestinal mucosa of Crohn’s disease were treated with either the HSP70 inhibitory peptide (aa 457–496) or peptides derived from CD40 and CD40L. These inhibitory peptides target the CD40–CD40L and the emerging CD40–HSP70 co-stimulatory pathway. Our findings offer a novel strategy to prevent excessive production of TNF-α in Crohn’s disease.
Intranasal IFNγ extends passive IgA antibody protection of mice againstMycobacterium tuberculosislung infection
Authors: Reljic R , Clark S O , Williams A , Falero-Diaz G , Singh M , Challacombe S , Marsh P D , Ivanyi J
Published: January 2006

Intranasal inoculation of mice with monoclonal IgA against the α-crystallin (acr1) antigen can diminish the tuberculous infection in the lungs. As this effect has been observed only over a short-term, we investigated if it could be extended by inoculation of IFNγ 3 days before infection, and further coinoculations with IgA, at 2 h before and 2 and 7 days after aerosol infection with Mycobacterium tuberculosis H37Rv. This treatment reduced the lung infection at 4 weeks more than either IgA or IFNγ alone (i.e. 17-fold, from 4·2 × 107 to 2·5 × 106 CFU, P = 0·006), accompanied also by lower granulomatous infiltration of the lungs. IFNγ added prior to infection of mouse peritoneal macrophages with IgA-opsonized bacilli resulted in a synergistic increase of nitric oxide and TNFα production and a 2–3 fold decrease in bacterial counts. Our improved results suggest, that combined treatment with IFNγ and IgA could be developed towards prophylactic treatment of AIDS patients, or as an adjunct to chemotherapy.
Predicting the influence of wolf‐provided carrion on scavenger community dynamics under climate change scenarios
Authors: WILMERS CHRISTOPHER C. , POST ERIC
Published: January 2006

Climate change poses an immediate threat to the persistence and distribution of many species, yet our ability to forecast changes in species composition is hindered by poor understanding of the extent to which higher trophic‐level interactions may buffer or exacerbate the adverse effects of warming. We incorporated species‐specific consumption data from 240 wolf‐killed elk carcasses from Yellowstone National Park into stochastic simulation models to link trends in the El Niño Southern Oscillation (ENSO) to food procurement by a guild of scavengers as a function of gray wolf reintroduction. We find that a shift in ENSO towards the El Niño (warming) phase of the cycle coincident with increasing global temperatures reduces carrion for scavengers, particularly those with strong seasonal patterns in resource use such as grizzly bears. Wolves alleviate these warming‐induced food shortages by rendering control over this crucial resource to biotic rather than abiotic factors. Ecosystems with intact top predators are likely to exhibit stronger biotic regulation and should be more resistant to climate change than ecosystems lacking them.
Emerging viral diseases and infectious disease risks
Authors: TAPPER M. L.
Published: January 2006

Summary.  New pathogens and antimicrobial‐resistant forms of older pathogens continue to emerge, some with the potential for rapid, global spread and high morbidity and mortality. Pathogens can emerge either through introduction into a new population or when the interaction with the vector changes; emergence is also influenced by microbiological adaptation and change, global travel patterns, domestic and wild animal contact and other variants in human ecology and behaviour. Quick, decisive action to detect and control novel pathogens, and thereby contain outbreaks and prevent further transmission, is frequently hampered by incomplete or inadequate data about a new or re‐emerging pathogen. Three examples of pathogens that are current causes for human health concern are avian influenza, West Nile virus (WNV) and the severe acute respiratory syndrome (SARS) coronavirus. Pathogens directly or indirectly transmitted by aerosolized droplets, such as avian influenza and SARS, pose considerable containment challenges. Rapid screening tests for other newly described pathogens such as WNV require time for development and may be <100% reliable. The importance of vigilance in the detection and control of newly recognized infectious threats cannot be overstressed. The presence of infectious agents in the blood supply could again have a significant impact on the safe use of both blood and blood‐derived products in the care of patients with haemophilia, as did the human immunodeficiency virus in the 1980s. Emerging pathogens will continue to be a reality requiring the collaborative efforts of public health and individual healthcare providers worldwide to contain outbreaks and prevent transmission.
Variant Creutzfeldt–Jakob disease: risk of transmission by blood transfusion and blood therapies
Authors: IRONSIDE J. W.
Published: January 2006

Summary.  In the last decade, a new variant of the human prion disease Creutzfeldt–Jakob disease (now known as variant CJD or vCJD) was identified and causally linked to dietary exposure to bovine spongiform encephalopathy (BSE) during the 1980s and early 1990s. Preliminary studies in animal models suggest that prions can be transmitted by blood. Based on two recent reports of iatrogenic vCJD transmission by blood transfusion in humans, a Department of Health‐sponsored risk assessment warned that recipients of plasma therapies are now at risk of contracting vCJD from potentially infected donors. It is believed that all the population may be susceptible to vCJD infection, although clinical cases have so far occurred only in methionine homozygotes at codon 129 in the human prion protein gene. A non‐invasive blood‐based diagnostic assay is urgently needed. Because the incubation period may be upwards of 40 years and there is no reliable screening test, it is currently unknown how many people may be in an asymptomatic phase of vCJD infection in the UK. However, there remains a distinct possibility that some infected patients may never develop clinical symptoms but will remain asymptomatic carriers who can potentially transmit the disease to other individuals. Therefore, screening of infectious individuals will be a critical component for individuals who rely on blood transfusions and/or blood therapies. In the absence of screening tests or effective therapies to treat this disease, a formidable worldwide public health challenge lies ahead to prevent new infections, accurately assess infection rates and treat infected patients.
Impact of a rheumatology expert nurse on the wellbeing of patients attending a drug monitoring clinic
Authors: Ryan Sarah , Hassell Andrew B. , Lewis Martyn , Farrell Adrian
Published: January 2006

Aim.  This paper reports a study to test the hypothesis that consultation with a clinical nurse specialist in a drug monitor clinic has a measurable impact on the well‐being of patients with rheumatoid arthritis.

Method.  A single blinded randomized controlled trial was carried out with 71 patients with rheumatoid arthritis who were starting new disease‐modifying anti‐rheumatic therapy at a district general hospital. Patients were randomized into two groups over a 3‐year recruitment period. Intervention group patients were monitored by a rheumatology clinical nurse specialist using Pendelton's framework to assess patient needs alongside safety monitoring. Control group patients were seen by an outpatient staff nurse for safety monitoring only over a 1‐year period. The primary outcome measures were the Arthritis Impact Measurement Scales and the Rheumatology Attitude Index. Data were also collected on the Disease Activity Score, number of consultations with healthcare professionals and changes in drug therapy. Data were collected at baseline, 3, 7 and 12 months between 1999 and 2002.

Results.  The Intervention group had greater change scores than the Control group for the Arthritis Impact Scale, with statistical significance shown at 7 months (P = 0·03). At 12 months the Rheumatology Attitude Index had improved by a mean of 1·8 in the Intervention group and deteriorated by 0·3 in the Control group. Changes in the Disease Activity Score were greater in the Intervention group at all time points, with statistical significance at 12 months (P = 0·048). There was little difference in the number of consultations or changes in drug therapy between the two groups.

Conclusion.  Consultation with an expert rheumatology nurse in a drug monitor clinic may add value in terms of improving patients’ perceived ability to cope with the arthritis.
Validity, trustworthiness and rigour: quality and the idea of qualitative research
Authors: Rolfe Gary
Published: January 2006

Aim.  In this paper, I call into question the widely‐held assumption of a single, more or less unified paradigm of ‘qualitative research’ whose methodologies share certain epistemological and ontological characteristics, and explore the implications of this position for judgements about the quality of research studies.

Background.  After a quarter of a century of debate in nursing about how best to judge the quality of qualitative research, we appear to be no closer to a consensus, or even to deciding whether it is appropriate to try to achieve a consensus. The literature on this issue can be broadly divided into three positions: those writers who wish qualitative research to be judged according to the same criteria as quantitative research; those who believe that a different set of criteria is required; and those who question the appropriateness of any predetermined criteria for judging qualitative research. Of the three positions, the second appears to have generated most debate, and a number of different frameworks and guidelines for judging the quality of qualitative research have been devised over recent years.

Discussion.  The second of the above positions is rejected in favour of the third. It argues that, if there is no unified qualitative research paradigm, then it makes little sense to attempt to establish a set of generic criteria for making quality judgements about qualitative research studies. We need either to acknowledge that the commonly perceived quantitative–qualitative dichotomy is in fact a continuum which requires a continuum of quality criteria, or to recognize that each study is individual and unique, and that the task of producing frameworks and predetermined criteria for assessing the quality of research studies is futile.

Conclusion.  Some of the implications of this latter position are explored, including the requirement that all published research reports should include a reflexive research diary.