bluuebunny/crossref_metadata_2025 huggingface dataset:
The CD20 homologue MS4A4 directs trafficking of KIT toward clathrin-independent endocytosis pathways and thus regulates receptor signaling and recycling
Authors: Cruse Glenn , Beaven Michael A. , Music Stephen C. , Bradding Peter , Gilfillan Alasdair M. , Metcalfe Dean D.
Published: February 2015

MS4A family members differentially regulate the cell cycle, and aberrant, or loss of, expression of MS4A family proteins has been observed in colon and lung cancer. However, the precise functions of MS4A family proteins and their mechanistic interactions remain unsolved. Here we report that MS4A4 facilitates trafficking of the receptor tyrosine kinase KIT through endocytic recycling rather than degradation pathways by a mechanism that involves recruitment of KIT to caveolin-1–enriched microdomains. Silencing of MS4A4 in human mast cells altered ligand-induced KIT endocytosis pathways and reduced receptor recycling to the cell surface, thus promoting KIT signaling in the endosomes while reducing that in the plasma membrane, as exemplified by Akt and PLCγ1 phosphorylation, respectively. The altered endocytic trafficking of KIT also resulted in an increase in SCF-induced mast cell proliferation and migration, which may reflect altered signaling in these cells. Our data reveal a novel function for MS4A family proteins in regulating trafficking and signaling, which could have implications in both proliferative and immunological diseases.
Dynamic actin filaments control the mechanical behavior of the human red blood cell membrane
Authors: Gokhin David S. , Nowak Roberta B. , Khoory Joseph A. , Piedra Alfonso de la , Ghiran Ionita C. , Fowler Velia M.
Published: February 2015

Short, uniform-length actin filaments function as structural nodes in the spectrin-actin membrane skeleton to optimize the biomechanical properties of red blood cells (RBCs). Despite the widespread assumption that RBC actin filaments are not dynamic (i.e., do not exchange subunits with G-actin in the cytosol), this assumption has never been rigorously tested. Here we show that a subpopulation of human RBC actin filaments is indeed dynamic, based on rhodamine-actin incorporation into filaments in resealed ghosts and fluorescence recovery after photobleaching (FRAP) analysis of actin filament mobility in intact RBCs (∼25–30% of total filaments). Cytochalasin-D inhibition of barbed-end exchange reduces rhodamine-actin incorporation and partially attenuates FRAP recovery, indicating functional interaction between actin subunit turnover at the single-filament level and mobility at the membrane-skeleton level. Moreover, perturbation of RBC actin filament assembly/disassembly with latrunculin-A or jasplakinolide induces an approximately twofold increase or ∼60% decrease, respectively, in soluble actin, resulting in altered membrane deformability, as determined by alterations in RBC transit time in a microfluidic channel assay, as well as by abnormalities in spontaneous membrane oscillations (flickering). These experiments identify a heretofore-unrecognized but functionally important subpopulation of RBC actin filaments, whose properties and architecture directly control the biomechanical properties of the RBC membrane.
6. Ritual as performance
Authors: Stephenson Barry
Published: February 2015

Cross-culturally, ritual typically includes elements commonly associated with performance events: music or rhythmic accompaniment; dance or other stylized bodily movements; and masking, costuming, and makeup. ‘Ritual as performance’ considers performance theory and performance studies and some of the work of significant theorists in these fields: J. L. Austin and Richard Schechner. By looking at the kōan tradition of Zen Buddhism, Schechner's approach to ritual can be better understood. Schechner places performance on a continuum that runs from efficacy to entertainment. The notions of embodiment and inscription in ritual studies are also considered along with the noetic implications of ritual action, such as pilgrimage.
7. The fortunes of ritual
Authors: Stephenson Barry
Published: February 2015

‘The fortunes of ritual’ charts the history of ritual, its study, and its reception beginning with the Confucian text Liji. This outlines means to counter humanity's fallen state through devices, guides, and practices called li, which are imagined as knots binding society together. Jumping to Enlightenment Europe, ritual came to be viewed as staid and outmoded, a superstitious remnant of a primitive past, a past that prevented humanity from truly advancing. In the early twentieth century, ritual was given some credibility via the Durkhemian tradition of social functionalism and Julian Huxley's causal connection between society's ills and ineffectual ritualization in society. Recent ritual theory articulates the relationship between ritual and group solidarity as seen through participation in contemporary festivals.
Guidance for RNA-seq co-expression network construction and analysis: safety in numbers
Authors: Ballouz S. , Verleyen W. , Gillis J.
Published: February 2015

Motivation: RNA-seq co-expression analysis is in its infancy and reasonable practices remain poorly defined. We assessed a variety of RNA-seq expression data to determine factors affecting functional connectivity and topology in co-expression networks.

Results: We examine RNA-seq co-expression data generated from 1970 RNA-seq samples using a Guilt-By-Association framework, in which genes are assessed for the tendency of co-expression to reflect shared function. Minimal experimental criteria to obtain performance on par with microarrays were >20 samples with read depth >10 M per sample. While the aggregate network constructed shows good performance (area under the receiver operator characteristic curve ∼0.71), the dependency on number of experiments used is nearly identical to that present in microarrays, suggesting thousands of samples are required to obtain ‘gold-standard’ co-expression. We find a major topological difference between RNA-seq and microarray co-expression in the form of low overlaps between hub-like genes from each network due to changes in the correlation of expression noise within each technology.

Contact:  jgillis@cshl.edu or sballouz@cshl.edu

Supplementary information: Networks are available at: http://gillislab.labsites.cshl.edu/supplements/rna-seq-networks/ and supplementary data are available at Bioinformatics online.
rSeqNP: a non-parametric approach for detecting differential expression and splicing from RNA-Seq data
Authors: Shi Yang , Chinnaiyan Arul M. , Jiang Hui
Published: February 2015

Summary: High-throughput sequencing of transcriptomes (RNA-Seq) has become a powerful tool to study gene expression. Here we present an R package, rSeqNP, which implements a non-parametric approach to test for differential expression and splicing from RNA-Seq data. rSeqNP uses permutation tests to access statistical significance and can be applied to a variety of experimental designs. By combining information across isoforms, rSeqNP is able to detect more differentially expressed or spliced genes from RNA-Seq data.

Availability and implementation: The R package with its source code and documentation are freely available at http://www-personal.umich.edu/∼jianghui/rseqnp/.

Contact:  jianghui@umich.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
CD1d-dependent expansion of NKT follicular helper cells in vivo and in vitro is a product of cellular proliferation and differentiation
Authors: Rampuria Pragya , Lang Mark L.
Published: February 2015

NKT follicular helper cells (NKTfh cells) are a recently discovered functional subset of CD1d-restricted NKT cells. Given the potential for NKTfh cells to promote specific antibody responses and germinal center reactions, there is much interest in determining the conditions under which NKTfh cells proliferate and/or differentiate in vivo and in vitro. We confirm that NKTfh cells expressing the canonical semi-invariant Vα14 TCR were CXCR5+/ICOS+/PD-1+/Bcl6+ and increased in number following administration of the CD1d-binding glycolipid α-galactosylceramide (α-GC) to C57Bl/6 mice. We show that the α-GC-stimulated increase in NKTfh cells was CD1d-dependent since the effect was diminished by reduced CD1d expression. In vivo and in vitro treatment with α-GC, singly or in combination with IL-2, showed that NKTfh cells increased in number to a greater extent than total NKT cells, but proliferation was near-identical in both populations. Acquisition of the NKTfh phenotype from an adoptively transferred PD-1-depleted cell population was also evident, showing that peripheral NKT cells differentiated into NKTfh cells. Therefore, the α-GC-stimulated, CD1d-dependent increase in peripheral NKTfh cells is a result of cellular proliferation and differentiation. These findings advance our understanding of the immune response following immunization with CD1d-binding glycolipids.
Oncocytic Adenocarcinoma of the Orbit
Authors: Harris Gerald J. , Paul Sean , Hunt Bryan C.
Published: February 2015

Oncocytic adenocarcinoma of the orbit is a rare tumor, with 1 case of nonlacrimal sac, nonlacrimal gland origin, and a poor outcome previously reported. An 85-year-old man with a 2-month history of left-sided epiphora, enlarging eyelid nodules, and diplopia in left gaze was found on imaging to have a poorly circumscribed, nodular mass of uniform radiodensity in the inferomedial orbit. Incisional biopsy revealed morphologic and immunohistochemical features of oncocytic adenocarcinoma with origin in the caruncle suspected, and CT of the neck, chest, abdomen, and pelvis showed no metastases or remote primary tumor source. Based on multidisciplinary consensus, orbital exenteration with adjuvant radiation therapy was performed, and there was no evidence of residual or recurrent tumor 2 years after treatment.
Cytokeratin-Negative Undifferentiated (Lymphoepithelial) Carcinoma of the Lacrimal Sac
Authors: Keelawat Somboon , Tirakunwichcha Suppapong , Saonanon Preamjit , Maneesri-leGrand Supang , Ruangvejvorachai Preecha , Lerdlum Sukalaya , Thorner Paul Scott
Published: February 2015

Epstein–Barr virus–associated undifferentiated (lymphoepithelial) carcinoma is a malignancy that most commonly arises in the nasopharynx but can also occur in other locations including the lacrimal sac. Generally, this tumor strongly expresses cytokeratin, making the diagnosis straightforward. In the absence of confirmatory immunohistochemistry, the diagnosis can be problematic, particularly for tumors arising in unusual locations. Only 3 cases arising in the lacrimal sac in association with Epstein–Barr virus have been reported in the English literature, and all showed typical pathologic findings. The authors report a fourth case, unique in that it showed negative immunostaining for all cytokeratins tested. The clue to the nature of the tumor came from identification of Epstein–Barr virus by in-situ hybridization and demonstration of tonofilaments by electron microscopy. This case demonstrates that a multimodal approach may be needed in the diagnosis of Epstein–Barr virus–associated carcinoma, especially when occurring in uncommon locations.
Ocular Penetration Secondary to Cocaine-Induced Midline Destructive Lesion
Authors: Kalin-Hajdu Evan , Allaire Guy , Boulos Patrick R.
Published: February 2015

Herein, the authors present a retrospective case report of a patient with ocular penetration due to cocaine-induced midline destructive lesion. To their knowledge, this is the first documented case of ocular penetration secondary to cocaine insufflation.
High Rate of Implementation of Proposed Actions for Improvement With the Healthcare Failure Mode Effect Analysis Method: Evaluation of 117 Analyses
Authors: Öhrn Annica , Ericsson Carin , Andersson Christer , Elfström Johan
Published: February 2015

Objectives

The aims of this study were to investigate what kind of impact the Healthcare Failure Mode Effect Analysis (HFMEA) had on the organization in 1 county council in Sweden and to evaluate the method of working for multidisciplinary teams performing HFMEA. Three main outcome measures were used: the quality of the documentation from the HFMEAs, fulfillment of the primary goal of the HFMEA, and, finally, whether proposed actions for improvement were implemented.

Methods

The study involved retrospective analysis of the documentation from 117 performed HFMEAs from 3 hospitals in the county council of Östergötland, Sweden, and interviews or questionnaires with team leaders and managers between 2006 and 2010.

Results

A proposed change in the organizational structure was the most common issue in the analyses. Eighty-nine percent of the written reports were of high quality. A median of 10 serious risks were detected, and 10 proposed actions (median) were made. In 78% of the HFMEAs, all or a large part of these had been implemented a few years afterward. We were unable to find factors that promoted the rate of implementation of proposed actions. Seventy-eight percent of the managers were completely satisfied with the results of the HFMEA. The mean cost per risk analysis was €1909.

Conclusions

Most of the proposed actions were implemented. The use of HFMEA can be improved using fewer team leaders but with more experience. The work involved in writing a report can be reduced without loss of impact on the organization.
Intergroup threat gates social attention in humans
Authors: Chen Yujie , Zhao Yufang
Published: February 2015

Humans shift their attention to follow another person's gaze direction, a phenomenon called gaze cueing. This study examined whether a particular social factor, intergroup threat, modulates gaze cueing. As expected, stronger responses of a particular in-group to a threatening out-group were observed when the in-group, conditioned to perceive threat from one of two out-groups, was presented with facial stimuli from the threatening and non-threatening out-groups. These results suggest that intergroup threat plays an important role in shaping social attention. Furthermore, larger gaze-cueing effects were found for threatening out-group faces than for in-group faces only at the 200 ms but not the 800 ms stimulus onset asynchrony (SOA); the specificity of the gaze-cueing effects at the short SOA suggests that threat cues modulate the involuntary component of gaze cueing.
Freud, Jung and Boas: the psychoanalytic engagement with anthropology revisited
Authors: Kenny Robert
Published: February 2015

Sigmund Freud's and C. G. Jung's turn to evolutionist anthropological material after 1909 is usually seen as a logical progression of their long-term interest in such material. It is also seen that they used this material ignorant of the significant challenges to the evolutionist paradigm underpinning such material, in particular the challenges led by Franz Boas. This paper argues otherwise: that both psychologists' turnings to such material was a new development, that neither had shown great interest in such material before 1909, and that their turnings to such material, far from being taken in ignorance of the challenges to evolutionist anthropology, were engagements with those challenges, because the evolutionist paradigm lay at the base of psychoanalysis. It argues that it is no coincidence that this engagement occurred after their return from America in 1909, where they had come into first-hand contact with the challenges of Franz Boas.
Lognormal Lorenz and normal receiver operating characteristic curves as mirror images
Authors: Irwin R. John , Hautus Michael J.
Published: February 2015

The Lorenz curve for assessing economic inequality depicts the relation between two cumulative distribution functions (CDFs), one for the distribution of incomes or wealth and the other for their first-moment distribution. By contrast, the receiver operating characteristic (ROC) curve for evaluating diagnostic systems depicts the relation between the complements of two CDFs, one for the distribution noise and the other for the distribution of signal plus noise. We demonstrate that the lognormal model of the Lorenz curve, which is often adopted to model the distribution of income and wealth, is a mirror image of the equal-variance normal model of the ROC curve, which is a fundamental model for evaluating diagnostic systems. The relationship between these two models extends the potential application of each. For example, the lognormal Lorenz curve can be used to evaluate diagnostic systems derived from equal-variance normal distributions.
High-intensity air-explosion-induced shock loading of structures: consideration of a real gas in modelling a nonlinear compressible medium
Authors: Ghoshal R. , Mitra N.
Published: February 2015

The existing practice of designing air-blast-resistant structures relies on the ideal gas model. But this model predicts the maximum value of the reflection coefficient (ratio of the reflected to the incident pressure) to be 8, whereas it can go up to 20 or more as reported in the literature. To address this discrepancy, air medium is modelled as a real gas instead of an ideal gas, where the effect of intermolecular forces, vibration, dissociation, electronic excitation and ionization are included. Ranges of peak over-pressure are identified where the ideal gas assumption cannot be used. Differences in impulse transmitted to the free-standing plates of different mass owing to relaxing of the ideal gas assumption and consideration of the real gas model are evaluated. Impulse transmitted to the structures for constant and variable back pressure (VBP) is also compared considering the real gas model. The result shows that for high-intensity shock, the ideal gas model under-predicts impulse transmitted to heavy plates but over-predicts the same for light-weight plates. Impulse transmitted to light-weight plates is also overestimated if VBP is neglected. The implications of this research are substantial for designing high-intensity air-blast mitigating structures, which if not considered properly, may lead to compromise in structural performance.
Genome reorganization in F
1
hybrids uncovers the role of retrotransposons in reproductive isolation
Authors: Senerchia Natacha , Felber François , Parisod Christian
Published: February 2015

Interspecific hybridization leads to new interactions among divergent genomes, revealing the nature of genetic incompatibilities having accumulated during and after the origin of species. Conflicts associated with misregulation of transposable elements (TEs) in hybrids expectedly result in their activation and genome-wide changes that may be key to species boundaries. Repetitive genomes of wild wheats have diverged under differential dynamics of specific long terminal repeat retrotransposons (LTR-RTs), offering unparalleled opportunities to address the underpinnings of plant genome reorganization by selfish sequences. Using reciprocal F
1
hybrids between three
Aegilops
species, restructuring and epigenetic repatterning was assessed at random and LTR-RT sequences with amplified fragment length polymorphism and sequence-specific amplified polymorphisms as well as their methylation-sensitive counterparts, respectively. Asymmetrical reorganization of LTR-RT families predicted to cause conflicting interactions matched differential survival of F
1
hybrids. Consistent with the genome shock model, increasing divergence of merged LTR-RTs yielded higher levels of changes in corresponding genome fractions and lead to repeated reorganization of LTR-RT sequences in F
1
hybrids. Such non-random reorganization of hybrid genomes is coherent with the necessary repression of incompatible TE loci in support of hybrid viability and indicates that TE-driven genomic conflicts may represent an overlooked factor supporting reproductive isolation.
Mechanical sensitivity reveals evolutionary dynamics of mechanical systems
Authors: Anderson P. S. L. , Patek S. N.
Published: February 2015

A classic question in evolutionary biology is how form–function relationships promote or limit diversification. Mechanical metrics, such as kinematic transmission (KT) in linkage systems, are useful tools for examining the evolution of form and function in a comparative context. The convergence of disparate systems on equivalent metric values (mechanical equivalence) has been highlighted as a source of potential morphological diversity under the assumption that morphology can evolve with minimal impact on function. However, this assumption does not account for mechanical sensitivity—the sensitivity of the metric to morphological changes in individual components of a structure. We examined the diversification of a four-bar linkage system in mantis shrimp (Stomatopoda), and found evidence for both mechanical equivalence and differential mechanical sensitivity. KT exhibited variable correlations with individual linkage components, highlighting the components that influence KT evolution, and the components that are free to evolve independently from KT and thereby contribute to the observed pattern of mechanical equivalence. Determining the mechanical sensitivity in a system leads to a deeper understanding of both functional convergence and morphological diversification. This study illustrates the importance of multi-level analyses in delineating the factors that limit and promote diversification in form–function systems.
Couple stresses and the fracture of rock
Authors: Atkinson Colin , Coman Ciprian D. , Aldazabal Javier
Published: February 2015

An assessment is made here of the role played by the micropolar continuum theory on the cracked Brazilian disc test used for determining rock fracture toughness. By analytically solving the corresponding mixed boundary-value problems and employing singular-perturbation arguments, we provide closed-form expressions for the energy release rate and the corresponding stress-intensity factors for both mode I and mode II loading. These theoretical results are augmented by a set of fracture toughness experiments on both sandstone and marble rocks. It is further shown that the morphology of the fracturing process in our centrally pre-cracked circular samples correlates very well with discrete element simulations.
On localization and void coalescence as a precursor to ductile fracture
Authors: Tekoğlu C. , Hutchinson J. W. , Pardoen T.
Published: February 2015

Two modes of plastic flow localization commonly occur in the ductile fracture of structural metals undergoing damage and failure by the mechanism involving void nucleation, growth and coalescence. The first mode consists of a macroscopic localization, usually linked to the softening effect of void nucleation and growth, in either a normal band or a shear band where the thickness of the band is comparable to void spacing. The second mode is coalescence with plastic strain localizing to the ligaments between voids by an internal necking process. The ductility of a material is tied to the strain at macroscopic localization, as this marks the limit of uniform straining at the macroscopic scale. The question addressed is whether macroscopic localization occurs prior to void coalescence or whether the two occur simultaneously. The relation between these two modes of localization is studied quantitatively in this paper using a three-dimensional elastic–plastic computational model representing a doubly periodic array of voids within a band confined between two semi-infinite outer blocks of the same material but without voids. At sufficiently high stress triaxiality, a clear separation exists between the two modes of localization. At lower stress triaxialities, the model predicts that the onset of macroscopic localization and coalescence occur simultaneously.
Material grain size and crack size influences on cleavage fracturing
Authors: Armstrong Ronald W.
Published: February 2015

A review is given of the analogous dependence on reciprocal square root of grain size or crack size of fracture strength measurements reported for steel and other potentially brittle materials. The two dependencies have much in common. For onset of cleavage in steel, attention is focused on relationship of the essentially athermal fracture stress compared with a quite different viscoplastic yield stress behaviour. Both grain-size-dependent stresses are accounted for in terms of dislocation pile-up mechanics. Lowering of the cleavage stress occurs in steel because of carbide cracking. For crack size dependence, there is complication of localized crack tip plasticity in fracture mechanics measurements. Crack-size-dependent conventional and indentation fracture mechanics measurements are described also for results obtained on the diverse materials: polymethylmethacrylate, silicon crystals, alumina polycrystals and WC-Co (cermet) composites.
Computational aspects of steel fracturing pertinent to naval requirements
Authors: Matic Peter , Geltmacher Andrew , Rath Bhakta
Published: February 2015

Modern high strength and ductile steels are a key element of US Navy ship structural technology. The development of these alloys spurred the development of modern structural integrity analysis methods over the past 70 years. Strength and ductility provided the designers and builders of navy surface ships and submarines with the opportunity to reduce ship structural weight, increase hull stiffness, increase damage resistance, improve construction practices and reduce maintenance costs. This paper reviews how analytical and computational tools, driving simulation methods and experimental techniques, were developed to provide ongoing insights into the material, damage and fracture characteristics of these alloys. The need to understand alloy fracture mechanics provided unique motivations to measure and model performance from structural to microstructural scales. This was done while accounting for the highly nonlinear behaviours of both materials and underlying fracture processes. Theoretical methods, data acquisition strategies, computational simulation and scientific imaging were applied to increasingly smaller scales and complex materials phenomena under deformation. Knowledge gained about fracture resistance was used to meet minimum fracture initiation, crack growth and crack arrest characteristics as part of overall structural integrity considerations.
Micromechanics of fracturing in nanoceramics
Authors: Ovid'ko I. A.
Published: February 2015

An overview of key experimental data and theoretical representations on fracture processes in nanoceramics is presented. The focuses are placed on crack growth in nanoceramics and their toughening micromechanics. Conventional toughening micromechanisms are discussed which effectively operate in both microcrystalline-matrix ceramics containing nanoinclusions and nanocrystalline-matrix ceramics. Particular attention is devoted to description of special (new) toughening micromechanisms related to nanoscale deformation occurring near crack tips in nanocrystalline-matrix ceramics. In addition, a new strategy for pronounced improvement of fracture toughness of ceramic materials through fabrication of ceramic–graphene nanocomposites is considered. Toughening micromechanisms are discussed which operate in such nanocomposites containing graphene platelets and/or few-layer sheets.
Microstructural mechanisms of cyclic deformation, fatigue crack initiation and early crack growth
Authors: Mughrabi Haël
Published: February 2015

In this survey, the origin of fatigue crack initiation and damage evolution in different metallic materials is discussed with emphasis on the responsible microstructural mechanisms. After a historical introduction, the stages of cyclic deformation which precede the onset of fatigue damage are reviewed. Different types of cyclic slip irreversibilities in the bulk that eventually lead to the initiation of fatigue cracks are discussed. Examples of trans- and intercrystalline fatigue damage evolution in the low cycle, high cycle and ultrahigh cycle fatigue regimes in mono- and polycrystalline face-centred cubic and body-centred cubic metals and alloys and in different engineering materials are presented, and some microstructural models of fatigue crack initiation and early crack growth are discussed. The basic difficulties in defining the transition from the initiation to the growth of fatigue cracks are emphasized. In ultrahigh cycle fatigue at very low loading amplitudes, the initiation of fatigue cracks generally occupies a major fraction of fatigue life and is hence life controlling.
Mechanical properties of micro- and nanocrystalline diamond foils
Authors: Lodes M. A. , Kachold F. S. , Rosiwal S. M.
Published: February 2015

Diamond coating of suitable template materials and subsequent delamination allows for the manufacturing of free-standing diamond foil. The evolution of the microstructure can be influenced by secondary nucleation via control of process conditions in the hot-filament chemical vapour deposition process. Bending tests show extraordinarily high strength (more than 8 GPa), especially for diamond foils with nanocrystalline structure. A detailed fractographic analysis is conducted in order to correlate measured strength values with crack-initiating defects. The size of the failure causing flaw can vary from tens of micrometres to tens of nanometres, depending on the diamond foil microstructure as well as the loading conditions.
Theory and modelling of diamond fracture from an atomic perspective
Authors: Brenner Donald W. , Shenderova Olga A.
Published: February 2015

Discussed in this paper are several theoretical and computational approaches that have been used to better understand the fracture of both single-crystal and polycrystalline diamond at the atomic level. The studies, which include first principles calculations, analytic models and molecular simulations, have been chosen to illustrate the different ways in which this problem has been approached, the conclusions and their reliability that have been reached by these methods, and how these theory and modelling methods can be effectively used together.
Fracture and fracture toughness of nanopolycrystalline metals produced by severe plastic deformation
Authors: Hohenwarter A. , Pippan R.
Published: February 2015

The knowledge of the fracture of bulk metallic materials developed in the last 50 years is mostly based on materials having grain sizes,d, in the range of some micrometres up to several hundred micrometres regarding the possibilities of classical metallurgical methods. Nowadays, novel techniques provide access to much smaller grain sizes, where severe plastic deformation (SPD) is one of the most significant techniques. This opens the door to extend basic research in fracture mechanics to the nanocrystalline (NC) grain size regime. From the technological point of view, there is also the necessity to evaluate standard fracture mechanics data of these new materials, such as the fracture toughness, in order to allow their implementation in engineering applications. Here, an overview of recent results on the fracture behaviour of several different ultrafine-grained (d<1 μm) and NC (d<100 nm) metals and alloys covering examples of body- and face-centred cubic structures produced by SPD will be given.
Restoration ofSp4in forebrain GABAergic neurons rescues hypersensitivity to ketamine inSp4hypomorphic mice
Authors: Higa Kerin K. , Ji Baohu , Buell Mahalah R. , Risbrough Victoria B. , Powell Susan B. , Young Jared W , Geyer Mark A. , Zhou Xianjin
Published: February 2015

Ketamine produces schizophrenia-like behavioral phenotypes in healthy people. Prolonged ketamine effects and exacerbation of symptoms were observed in schizophrenia patients after administration of ketamine. More recently, ketamine has been used as a potent antidepressant to treat patients with major depression. The genes and neurons that regulate behavioral responses to ketamine, however, remain poorly understood. Our previous studies found thatSp4hypomorphic mice displayed several behavioral phenotypes relevant to psychiatric disorders, consistent with humanSP4gene associations with schizophrenia, bipolar, and major depression. Among those behavioral phenotypes, hypersensitivity to ketamine-induced hyperlocomotion has been observed inSp4hypomorphic mice. Here, we report differential genetic restoration ofSp4expression in forebrain excitatory neurons or GABAergic neurons inSp4hypomorphic mice and the effects of these restorations on different behavioral phenotypes. Restoration ofSp4in forebrain excitatory neurons did not rescue deficient sensorimotor gating, fear learning, or ketamine-induced hyperlocomotion. Restoration ofSp4in forebrain GABAergic neurons, however, rescued ketamine-induced hyperlocomotion, but did not rescue deficient sensorimotor gating or fear learning. Our studies suggest that theSp4gene in forebrain GABAergic neurons plays an essential role in regulating some behavioral responses to ketamine.
Photoprotection Conferred by Changes in Photosynthetic Protein Levels and Organization during Dehydration of a Homoiochlorophyllous Resurrection Plant
Authors: Charuvi Dana , Nevo Reinat , Shimoni Eyal , Naveh Leah , Zia Ahmad , Adam Zach , Farrant Jill M. , Kirchhoff Helmut , Reich Ziv
Published: February 2015

During desiccation, homoiochlorophyllous resurrection plants retain most of their photosynthetic apparatus, allowing them to resume photosynthetic activity quickly upon water availability. These plants rely on various mechanisms to prevent the formation of reactive oxygen species and/or protect their tissues from the damage they inflict. In this work, we addressed the issue of how homoiochlorophyllous resurrection plants deal with the problem of excessive excitation/electron pressures during dehydration using Craterostigma pumilum as a model plant. To investigate the alterations in the supramolecular organization of photosynthetic protein complexes, we examined cryoimmobilized, freeze-fractured leaf tissues using (cryo)scanning electron microscopy. These examinations revealed rearrangements of photosystem II (PSII) complexes, including a lowered density during moderate dehydration, consistent with a lower level of PSII proteins, as shown by biochemical analyses. The latter also showed a considerable decrease in the level of cytochrome f early during dehydration, suggesting that initial regulation of the inhibition of electron transport is achieved via the cytochrome b  6  f complex. Upon further dehydration, PSII complexes are observed to arrange into rows and semicrystalline arrays, which correlates with the significant accumulation of sucrose and the appearance of inverted hexagonal lipid phases within the membranes. As opposed to PSII and cytochrome f, the light-harvesting antenna complexes of PSII remain stable throughout the course of dehydration. Altogether, these results, along with photosynthetic activity measurements, suggest that the protection of retained photosynthetic components is achieved, at least in part, via the structural rearrangements of PSII and (likely) light-harvesting antenna complexes into a photochemically quenched state.
Structure of a highly acidic β-lactamase from the moderate halophileChromohalobactersp. 560 and the discovery of a Cs+-selective binding site
Authors: Arai Shigeki , Yonezawa Yasushi , Okazaki Nobuo , Matsumoto Fumiko , Shibazaki Chie , Shimizu Rumi , Yamada Mitsugu , Adachi Motoyasu , Tamada Taro , Kawamoto Masahide , Tokunaga Hiroko , Ishibashi Matsujiro , Blaber Michael , Tokunaga Masao , Kuroki Ryota
Published: February 2015

Environmentally friendly absorbents are needed for Sr2+and Cs+, as the removal of the radioactive Sr2+and Cs+that has leaked from the Fukushima Nuclear Power Plant is one of the most important problems in Japan. Halophilic proteins are known to have many acidic residues on their surface that can provide specific binding sites for metal ions such as Cs+or Sr2+. The crystal structure of a halophilic β-lactamase fromChromohalobactersp. 560 (HaBLA) was determined to resolutions of between 1.8 and 2.9 Å in space groupP31using X-ray crystallography. Moreover, the locations of bound Sr2+and Cs+ions were identified by anomalous X-ray diffraction. The location of one Cs+-specific binding site was identified in HaBLA even in the presence of a ninefold molar excess of Na+(90 mMNa+/10 mMCs+). From an activity assay using isothermal titration calorimetry, the bound Sr2+and Cs+ions do not significantly affect the enzymatic function of HaBLA. The observation of a selective and high-affinity Cs+-binding site provides important information that is useful for the design of artificial Cs+-binding sites that may be useful in the bioremediation of radioactive isotopes.
An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase
Authors: Wong Jaslyn E. M. M. , Midtgaard Søren Roi , Gysel Kira , Thygesen Mikkel B. , Sørensen Kasper K. , Jensen Knud J. , Stougaard Jens , Thirup Søren , Blaise Mickaël
Published: February 2015

LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containingN-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of theThermus thermophilusNlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized withN-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.
Structure of Csd3 fromHelicobacter pylori, a cell shape-determining metallopeptidase
Authors: An Doo Ri , Kim Hyoun Sook , Kim Jieun , Im Ha Na , Yoon Hye Jin , Yoon Ji Young , Jang Jun Young , Hesek Dusan , Lee Mijoon , Mobashery Shahriar , Kim Soon-Jong , Lee Byung Il , Suh Se Won
Published: February 2015

Helicobacter pyloriis associated with various gastrointestinal diseases such as gastritis, ulcers and gastric cancer. Its colonization of the human gastric mucosa requires high motility, which depends on its helical cell shape. Seven cell shape-determining genes (csd1,csd2,csd3/hdpA,ccmA,csd4,csd5andcsd6) have been identified inH. pylori. Their proteins play key roles in determining the cell shape through modifications of the cell-wall peptidoglycan by the alteration of cross-linking or by the trimming of peptidoglycan muropeptides. Among them, Csd3 (also known as HdpA) is a bifunctional enzyme. Its D,D-endopeptidase activity cleaves the D-Ala4-mDAP3peptide bond between cross-linked muramyl tetrapeptides and pentapeptides. It is also a D,D-carboxypeptidase that cleaves off the terminal D-Ala5from the muramyl pentapeptide. Here, the crystal structure of this protein has been determined, revealing the organization of its three domains in a latent and inactive state. The N-terminal domain 1 and the core of domain 2 share the same fold despite a very low level of sequence identity, and their surface-charge distributions are different. The C-terminal LytM domain contains the catalytic site with a Zn2+ion, like the similar domains of other M23 metallopeptidases. Domain 1 occludes the active site of the LytM domain. The core of domain 2 is held against the LytM domain by the C-terminal tail region that protrudes from the LytM domain.
Brickworxbuilds recurrent RNA and DNA structural motifs into medium- and low-resolution electron-density maps
Authors: Chojnowski Grzegorz , Waleń Tomasz , Piątkowski Paweł , Potrzebowski Wojciech , Bujnicki Janusz M.
Published: February 2015

Brickworxis a computer program that builds crystal structure models of nucleic acid molecules using recurrent motifs including double-stranded helices. In a first step, the program searches for electron-density peaks that may correspond to phosphate groups; it may also take into account phosphate-group positions provided by the user. Subsequently, comparing the three-dimensional patterns of the P atoms with a database of nucleic acid fragments, it finds the matching positions of the double-stranded helical motifs (A-RNA or B-DNA) in the unit cell. If the target structure is RNA, the helical fragments are further extended with recurrent RNA motifs from a fragment library that contains single-stranded segments. Finally, the matched motifs are merged and refined in real space to find the most likely conformations, including a fit of the sequence to the electron-density map. TheBrickworxprogram is available for download and as a web server at http://iimcb.genesilico.pl/brickworx.
Developing a dual diagnosis service in Cork, Ireland by way of participatory action research (PAR)
Authors: Connolly John , MacGabhann Liam , McKeown Olive
Published: February 2015

Purpose

– Developing a dual diagnosis service in Cork, Ireland by way of participatory action research (PAR) background: internationally there is a growing consensus regarding the ideal of integrated treatment. In Ireland, recommendations identified the need for multi-disciplinary team integration and client participation being central to service development. Such recommendations collectively fit most appropriately with PAR, the methodological and theoretical framework best suited to achieve the objectives of the inquiry. PAR's inclusive philosophy creates processes of negotiation, self-reflexivity and exploration of power issues with the lived experience of communities. Key elements of this approach facilitate the development of emancipatory and participatory democracy whilst highlighting identified social issues through research, learning and action. The paper aims to discuss these issues.

Design/methodology/approach

– Cyclical processes of planning, action, observation and reflection in cycle one have facilitated the introduction of PAR's methodological framework into the existing public health (Health Service Executive) system of primary care addiction and mental health services. Developing stakeholder relationships in decision making processes has been pivotal in cycle 1 as the process of collective engagement evolves. Stakeholders begin to experience their collective participation in the methods adopted and a collective sense of ownership and commitment to the iterative process begins to take shape. Stakeholders in cycle 1 have participated in multiple data generation methods including: informal interviews, planned discussion and focus groups, multidisciplinary team meetings, testimonials, observations and reflections.

Findings

– Cycle 1 of this PAR inquiry has engaged stakeholders (service users and their families, practitioners including; academic/practitioners, a consultant psychiatrist, psychologist, mental health nurses, an occupational therapist, psychotherapists, an acupuncturist, an addiction counsellor, an art therapist) in an integrated process of inquiry. PAR methods adopted in this cycle have facilitated particular dual diagnosis service developments and emerging initiatives (previously unidentified). Actions collaboratively planned for and illustrated in this paper include: the implementation of a psychotherapy group and implementing direct access to an acupuncture clinic.

Originality/value

– Stakeholders collaboratively experience PAR's methodological and theoretical approach which has facilitated service developments in cycle 1 of the inquiry. This sets the stage for the completion of actions already in motion and for further initiatives to continue to evolve as cycle 2 processes emerge.
EMDR treatment for PTSD and Intellectual Disability: a case study
Authors: Barrowcliff Alastair L. , Evans Gemma A. L
Published: February 2015

Purpose

– The purpose of this paper is to provide a detailed description of an adapted Eye-Movement Desensitisation and Reprocessing (EMDR) intervention in the treatment of chronic Post-Traumatic Stress Disorder (PTSD) in an individual with moderate-severe Intellectual Disability (ID), blindness, and Mucopolysaccharidosis Hunters Syndrome.

Design/methodology/approach

– A case study reporting on the implementation of an eight phase EMDR approach adapted for intellectual and sensory requirements. The intervention involved a series of preparatory meetings and four sessions of EMDR.

Findings

– The intervention was successful in ameliorating most symptoms attributed to a PTSD presentation.

Research limitations/implications

– The availability of the full breadth of treatment options for PTSD as indicated in National Institute for Health and Care Excellence (2005) is questionable in clinical practice with individuals with ID. Appropriate investment in research determining the most efficacious interventions for this clinical population is required.

Originality/value

– This case study addresses issues of complexity in respect of the assessment and treatment of trauma in an ID population. It raises a number of important social/research questions in addition to providing a high level of detail in regard to the adaptations required to deliver EMDR for a complex individual whilst retaining fidelity to the standard treatment model.
Checking the manipulation checks in information security research
Authors: Marett Kent
Published: February 2015

Purpose

– An increasing amount of attention is being paid to the human side of information security programs, leading to research designs that require the manipulation of study variables. The purpose of this paper is to highlight a traditional assessment of such designs, the manipulation check, and examine how its absence can undermine otherwise solid research efforts.

Design/methodology/approach

– This paper reviews literature from the fields of research methods, organizational behavior and information systems for extant perspectives and viewpoints on manipulation checks, which are then brought into the realm of information security research.

Findings

– The possible risks involved with failing to perform manipulation checks are discussed, which include a possibility of making Type II errors. The paper provides further insight on the timing, method and manner in which manipulation checks can be performed.

Originality/value

– A disappointing number of research articles in the area of information security fail to report manipulation checks when they should. This paper seeks to remind researchers to perform this vital assessment and to use the results accordingly.
Risk perception matters: why women’s passion may not lead to a business start-up
Authors: Dalborg Cecilia , von Friedrichs Yvonne , Wincent Joakim
Published: February 2015

Purpose

– This paper aims to explore whether nascent women entrepreneurs perceive more risks than men, and to determine how higher risk perceptions might limit start-up decisions by mediating the potential influence of passion and self-efficacy.

Design/methodology/approach

– This study surveyed 103 participants in Sweden – both women and men – who, in the period 2008 through 2011, intended to start a business. ANOVA tests and binominal logistic regression models were conducted to test hypothesized framework.

Findings

– The authors found that nascent women entrepreneurs perceive more risk than nascent male entrepreneurs, that risk perceptions influence start-up decisions and that risk preferences partial out the otherwise identified influence of passion on start-up decisions.

Research limitations/implications

– The authors reveal a consequence of gender socialization and how it impacts the start-up decisions of nascent women entrepreneurs. Support systems should consider developing activities that change the public’s perception of who is an entrepreneur and seek ways to balance risk perceptions between men and women.

Originality/value

– The authors argue here that risk perceptions play a prominent role in start-up decisions. Specifically, they consider that nascent women entrepreneurs perceive more risks than men, and that their view of risk partials out any potential influence of their perceived passion and self-efficacy on their start-up decision.