bluuebunny/crossref_metadata_2025 huggingface dataset:
Organising the soundscape
Authors: Rauniomaa Mirka , Heinemann Trine
Published: August 2014

This chapter examines two auditory objects, i.e. devices that produce sounds when in use: audio entertainment systems and vacuum cleaners. Despite their apparent differences, both objects raise similar relevancies for how and when they are employed. The chapter demonstrates that participants treat the turning on of an auditory object as negotiable and requiring disengagement from other involvements, such as talk. Consequently, turning on an auditory object occurs typically at points where the participants have brought a previous interactional activity to a close collaboratively and where the possibility of turning on the auditory object has been explicated either verbally or physically
Cultivating objects in interaction
Authors: Hazel Spencer
Published: August 2014

This chapter explores patterns of repeated orientations to physical objects in interactants’ visuo-spatial and haptic surround. A number of examples are presented from advice-giving activities in various institutional settings, where participants-in-interaction initially draw on material objects at hand while pursuing a particular line of explanation, and then return to these objects at later intervals. The analysis suggests that the objects are afforded representational properties through their being anchored to some referent in the talk, and that participants subsequently draw on these associations for describing, disambiguating or clarifying aspects of the relatively complex procedural frameworks discussed in the settings. This suggests that the temporal stability of material objects available to participants makes them an ideal resource to be developed as visual motifs.
To follow the materials
Authors: Ekström Anna , Lindwall Oskar
Published: August 2014

This chapter investigates the role and function of textile materials in relation to corrective sequences in craft education. The analyses explicate how problems are detected, how problems are diagnosed and how problems are corrected and solved. When students encounter problems related to their making of a textile object, there is a disruption in the progression of the activity. Disruptions in progressivity in the analysed setting are not heard in intervening talk, but seen in the ways the materials have turned out. Correspondingly, actions used to overcome these problems, whether conducted in talk or otherwise, are not done on talk but on actions and materials involved in the making of objects.
Artworks as touchable objects
Authors: Kreplak Yaël , Mondémé Chloé
Published: August 2014

In this chapter we contribute to the description of the interactional accomplishment of object use, by raising the following question “what kind of objects are artworks?”, and consequently, “what kind of interactional practices do they configure?”. By focusing on video-analysis of a guided tour for visually impaired persons (VIPs) allowed to touch artworks, we propose a praxeological analysis of situated procedures of artworks’ formulation and palpation, opening on a reflection on aesthetic touch – both about the way it is reflexively accomplished and the way tactile experience is collectively and sequentially organised in interaction.
Incidental and essential objects in interaction
Authors: Weilenmann Alexandra , Lymer Gustav
Published: August 2014

A large body of work points to the special status of paper documents in the ecology of objects in the workplace. In this chapter, we revisit this work, focusing on the role of paper in the everyday work of journalists. We examine three quite different empirical examples where paper documents feature in interaction, supporting, in turn, the structuring of conversation, collaboration and inter-organisational interaction. Based on these examples we argue for a distinction between object-focused interactions and object-implicating interactions. In addition, and related to the dual nature of documents being both material objects and carriers of information, we identify an analytic dimension along which interactions with objects can be placed, that from incidental to essential.
Instructed objects
Authors: Koschmann Timothy , Zemel Alan
Published: August 2014

This chapter develops an ethnomethodologically-informed view regarding the sociality of objects, building upon Garfinkel’s various descriptions of object constitution. We examine a particular case of diagnostic reasoning produced in the course of carrying out a surgical procedure at a teaching hospital. Our interest is in the methods employed by the surgeons in resolving certain incongruities in the case as it presents itself. Through an occasioned process of inquiry, the case at hand comes to be seen in a new light. This revised clinical picture is the oriented object under consideration here and it is produced as a discovered matter. We describe it as an instructed object to emphasise that perception is a kind of action and can too be taught. For us, as for Garfinkel, instruction is a fundamental feature of how social order is created and shared understanding sustained. In the analysed example, the methods by which a new appreciation of the case is achieved are public and inspectable. Instructional settings are, in this way, ‘perspicuous sites’ for investigating how “a world of meant objects” is produced.
Epstein–Barr virus nuclear antigen 3A protein regulates CDKN2B transcription via interaction with MIZ-1
Authors: Bazot Quentin , Deschamps Thibaut , Tafforeau Lionel , Siouda Maha , Leblanc Pascal , Harth-Hertle Marie L. , Rabourdin-Combe Chantal , Lotteau Vincent , Kempkes Bettina , Tommasino Massimo , Gruffat Henri , Manet Evelyne
Published: August 2014

The Epstein–Barr virus (EBV) nuclear antigen 3 family of protein is critical for the EBV-induced primary B-cell growth transformation process. Using a yeast two-hybrid screen we identified 22 novel cellular partners of the EBNA3s. Most importantly, among the newly identified partners, five are known to play direct and important roles in transcriptional regulation. Of these, the Myc-interacting zinc finger protein-1 (MIZ-1) is a transcription factor initially characterized as a binding partner of MYC. MIZ-1 activates the transcription of a number of target genes including the cell cycle inhibitor CDKN2B. Focusing on the EBNA3A/MIZ-1 interaction we demonstrate that binding occurs in EBV-infected cells expressing both proteins at endogenous physiological levels and that in the presence of EBNA3A, a significant fraction of MIZ-1 translocates from the cytoplasm to the nucleus. Moreover, we show that a trimeric complex composed of a MIZ-1 recognition DNA element, MIZ-1 and EBNA3A can be formed, and that interaction of MIZ-1 with nucleophosmin (NPM), one of its coactivator, is prevented by EBNA3A. Finally, we show that, in the presence of EBNA3A, expression of the MIZ-1 target gene, CDKN2B, is downregulated and repressive H3K27 marks are established on its promoter region suggesting that EBNA3A directly counteracts the growth inhibitory action of MIZ-1.
Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains
Authors: Jost Daniel , Carrivain Pascal , Cavalli Giacomo , Vaillant Cédric
Published: August 2014

Genomes of eukaryotes are partitioned into domains of functionally distinct chromatin states. These domains are stably inherited across many cell generations and can be remodeled in response to developmental and external cues, hence contributing to the robustness and plasticity of expression patterns and cell phenotypes. Remarkably, recent studies indicate that these 1D epigenomic domains tend to fold into 3D topologically associated domains forming specialized nuclear chromatin compartments. However, the general mechanisms behind such compartmentalization including the contribution of epigenetic regulation remain unclear. Here, we address the question of the coupling between chromatin folding and epigenome. Using polymer physics, we analyze the properties of a block copolymer model that accounts for local epigenomic information. Considering copolymers build from the epigenomic landscape of Drosophila, we observe a very good agreement with the folding patterns observed in chromosome conformation capture experiments. Moreover, this model provides a physical basis for the existence of multistability in epigenome folding at sub-chromosomal scale. We show how experiments are fully consistent with multistable conformations where topologically associated domains of the same epigenomic state interact dynamically with each other. Our approach provides a general framework to improve our understanding of chromatin folding during cell cycle and differentiation and its relation to epigenetics.
Pulsations of pre-white dwarfs with hydrogen-dominated atmospheres
Authors: Maeda Kazuhiro , Shibahashi Hiromoto
Published: August 2014

We carried out a fully non-adiabatic analysis for nonradial oscillations of pre-white dwarfs evolved from the post-Asymptotic Giant Branch (AGB) with hydrogen-dominated envelopes. It is shown that nuclear reactions in the hydrogen burning shell excite low-degree g-modes in the period range of about 40–200 s for the pre-white dwarf models with Teff = 40000 K–300000 K. It is also shown that the amount of hydrogen has a significant influence on the instability domain of such pre-white dwarfs in the Hertzsprung-Russel (H-R) diagram. Thus, the thickness of hydrogen-dominated envelopes may be well constrained by observing the presence of the g-mode oscillations.
Distributions of molecules in the circumnuclear disk and surrounding starburst ring in the Seyfert galaxy NGC 1068 observed with ALMA
Authors: Takano Shuro , Nakajima Taku , Kohno Kotaro , Harada Nanase , Herbst Eric , Tamura Yoichi , Izumi Takuma , Taniguchi Akio , Tosaki Tomoka
Published: August 2014

Sensitive observations with the Atacama Large Millimeter/submillimeter Array (ALMA) allow astronomers to observe the detailed distributions of molecules with relatively weak intensity in nearby galaxies. In particular, we report distributions of several molecular transitions including shock and dust related species (13CO J = 1–0, C18O J = 1–0, 13CN N = 1–0, CS J = 2–1, SO JN = 32–21, HNCO JKa,Kc = 50,5–40,4, HC3N J = 11–10, 12–11, CH3OH JK = 2K–1K, and CH3CN JK = 6K–5K) in the nearby Seyfert 2 galaxy NGC 1068 observed with the ALMA early science program. The central ∼ 1′(∼ 4.3 kpc) of this galaxy was observed in the 100-GHz region covering ∼ 96–100 GHz and ∼ 108–111 GHz with an angular resolution of ∼ 4′′ × 2′′ (290 pc × 140 pc) to study the effects of an active galactic nucleus and its surrounding starburst ring on molecular abundances. Here, we present images and report a classification of molecular distributions into three main categories: (1) molecules concentrated in the circumnuclear disk (CND) (SO JN = 32–21, HC3N J = 11–10, 12–11, and CH3CN JK = 6K–5K), (2) molecules distributed both in the CND and the starburst ring (CS J = 2–1 and CH3OH JK = 2K–1K), and (3) molecules distributed mainly in the starburst ring (13CO J = 1–0 and C18O J = 1–0). Since most of the molecules such as HC3N observed in the CND are easily dissociated by UV photons and X-rays, our results indicate that these molecules must be effectively shielded. In the starburst ring, the relative intensity of methanol at each clumpy region is not consistent with those of 13CO, C18O, or CS. This difference is probably caused by the unique formation and destruction mechanisms of CH3OH.
Language as a multimodal phenomenon: implications for language learning, processing and evolution
Authors: Vigliocco Gabriella , Perniss Pamela , Vinson David
Published: August 2014

Our understanding of the cognitive and neural underpinnings of language has traditionally been firmly based on spoken Indo-European languages and on language studied as speech or text. However, in face-to-face communication, language is multimodal: speech signals are invariably accompanied by visual information on the face and in manual gestures, and sign languages deploy multiple channels (hands, face and body) in utterance construction. Moreover, the narrow focus on spoken Indo-European languages has entrenched the assumption that language is comprised wholly by an arbitrary system of symbols and rules. However, iconicity (i.e. resemblance between aspects of communicative form and meaning) is also present: speakers use iconic gestures when they speak; many non-Indo-European spoken languages exhibit a substantial amount of iconicity in word forms and, finally, iconicity is the norm, rather than the exception in sign languages. This introduction provides the motivation for taking a multimodal approach to the study of language learning, processing and evolution, and discusses the broad implications of shifting our current dominant approaches and assumptions to encompass multimodal expression in both signed and spoken languages.
Iconicity as structure mapping
Authors: Emmorey Karen
Published: August 2014

Linguistic and psycholinguistic evidence is presented to support the use of structure-mapping theory as a framework for understanding effects of iconicity on sign language grammar and processing. The existence of
structured
mappings between phonological form and semantic mental representations has been shown to explain the nature of metaphor and pronominal anaphora in sign languages. With respect to processing, it is argued that psycholinguistic effects of iconicity may only be observed when the task specifically taps into such structured mappings. In addition, language acquisition effects may only be observed when the relevant cognitive abilities are in place (e.g. the ability to make structural comparisons) and when the relevant conceptual knowledge has been acquired (i.e. information key to processing the iconic mapping). Finally, it is suggested that iconicity is better understood as a structured mapping between two mental representations than as a link between linguistic form and human experience.
Crystal structure of 1H-imidazol-3-ium 2-(1,3-dioxoisoindolin-2-yl)acetate
Authors: Mohamed Shaaban K. , Akkurt Mehmet , Potgieter Herman , Ali Muizz
Published: August 2014

The title salt, C3H5N2+·C10H6NO4−, was obtained during a study of the co-crystallization ofN′-[bis(1H-imidazol-1-yl)methylene]isonicotinohydrazide with (1,3-dioxoisoindolin-2-yl)acetic acid under aqueous conditions. The 1,3-dioxoisoindolinyl ring system of the anion is essentially planar [maximum deviation = 0.023 (2) Å]. In the crystal, cations and anions are linkedviaclassical N—H...O hydrogen bonds and weak C—H...O hydrogen bonds, forming a three-dimensional network. Weak C—H...π interactions and π–π stacking interactions [centroid–centroid distances = 3.4728 (13) and 3.7339 (13) Å] also occur in the crystal.
Did they ‘Read Before Burning’? The Coalition and Quangos
Authors: DOMMETT KATHARINE , FLINDERS MATTHEW , SKELCHER CHRIS , TONKISS KATHERINE
Published: August 2014

Attitudes to quangos are paradoxical. On the one hand they are perceived to be undemocratic, unaccountable organisations, while on the other they are seen to improve effectiveness, limit political interference and increase public confidence in government. This paradox is reflected in the behaviour of political parties, which generally adopt a harsh line towards quangos in opposition, but come to rely on these bodies in office. Ahead of the 2010 general election it was, however, noticeable that the Conservative party rejected this dynamic by promising to pursue ‘a more sophisticated approach’. This article explores the Coalition government's subsequent ‘public bodies reform programme’, assessing its progress against recommendations contained within the Institute for Government's Read before Burning report of July 2010. It concludes that while the Coalition has addressed long‐standing concerns about the day‐to‐day governance of public bodies, it has failed to resolve a set of broader and strategic (metagovernance) issues.
Putting Neoliberalism in its Place
Authors: CROUCH COLIN
Published: August 2014

Neoliberalism is not as popular as its opponents seem so much to fear; in democratic politics it nearly always hides behind other ideologies and policy types, as its essential message that we should pursue no goals that cannot be achieved through the market is intrinsically unattractive to the majority of people. Its power lies in the wealth of its key supporters, and in the difficulty of raising coordinated opposition to it among post‐industrial populations that have little sense of their political interests. The main base for hope of change in this comes from the as yet unrealised potential of women's movements.
Quangos—Why Bother Counting Them When Whitehall Can't?
Authors: WALKER DAVID
Published: August 2014

‘Mindless’ empiricism rules in British central government, bolstered by the use of prerogative powers and the absence of any ‘court of appeal’ to insist on definitions and uniformities. This gives arguments about quangos—arm's‐length bodies—a surreal quality. The Cameron coalition has created many new quangos, while claiming a cull. Unless and until Whitehall acquires, or is forced to acquire, better habits of mind, it may be a waste of time for academics and reformers to prepare taxonomies and call for more administrative rationality.
RIP RIPA? Snowden, Surveillance, and the Inadequacies of our Existing Legal Framework
Authors: MOORE MARTIN
Published: August 2014

This collection of pieces addresses questions raised by the Snowden revelations and their aftermath. All the authors were participants at a round‐table discussion at King's College London on Thursday 20 March 2014. The round table was chaired jointly by Sir Lawrence Freedman and Lord [Peter] Hennessy. Those participating were: Baroness [Onora] O'Neill, Lord [Ken] Macdonald, Nigel Inkster, Professor Thomas Rid (King's College), Ewen MacAskill (The Guardian), Gordon Corera (BBC), Jemima Stratford QC, Peter Horrocks (BBC), Charlie Edwards (RUSI), Professor Jean Seaton (Westminster University), Bill Peace (King's, ex‐SOCA), Air Vice‐Marshal Andrew Vallance (DA‐Notice), Carl Miller (DEMOS/King's), Lord (Alex) Carlile and Richard Sambrook (Cardiff University).

The round table was organised by Martin Moore, director of the Media Standards Trust, and Benedict Wilson, lecturer in Defence Studies at King's and Research Associate at KPI. It was a joint Media Standards Trust–King's Policy Institute Event. For more information please contact martin.moore@mediastandardstrust.org or benedict.wilson@kcl.ac.uk.
Investigation of sporulation in the Desulfotomaculum genus: a genomic comparison with the genera Bacillus and Clostridium
Authors: Dalla Vecchia Elena , Visser Michael , Stams Alfons J. M. , Bernier‐Latmani Rizlan
Published: August 2014

The genus Desulfotomaculum, belonging to the Firmicutes, comprises strictly anaerobic and endospore‐forming bacteria capable of dissimilatory sulfate reduction. These microorganisms are metabolically versatile and are widely distributed in the environment. Spore formation allows them to survive prolonged environmental stress. Information on the mechanism of sporulation in Desulfotomaculum species is scarce. Herein, this process was probed from a genomic standpoint, using the Bacillus subtilis model system as a reference and clostridial sporulation for comparison. Desulfotomaculum falls somewhere in between the Bacillus and Clostridium in terms of conservation of sporulation proteins. Furthermore, it showcased the conservation of a core regulatory cascade throughout genera, while uncovering variability in the initiation of sporulation and the structural characteristics of spores from different genera. In particular, while in Clostridium species sporulation is not initiated by a phosphorelay, Desulfotomaculum species harbour homologues of the B. subtilis proteins involved in this process. Conversely, both Clostridium and Desulfotomaculum species conserve very few B. subtilis structural proteins, particularly those found in the outer layers of the spore. Desulfotomaculum species seem to share greater similarity to the outer layers of Clostridium difficile.
Single nucleotide polymorphisms in the insulin‐like growth factor 1 (IGF1) gene are associated with growth‐related traits in farmed Atlantic salmon
Authors: Tsai H. Y. , Hamilton A. , Guy D. R. , Houston R. D.
Published: August 2014

Understanding the genetic basis of variation in traits related to growth and fillet quality in Atlantic salmon is of importance to the aquaculture industry. Several growth‐related QTL have been identified via the application of genetic markers. The IGF1 gene is considered a highly conserved and crucial growth‐regulating gene in salmonid species. However, the association between polymorphisms in the IGF1 gene and growth‐related traits in Atlantic salmon is unknown. Therefore, in this study, regions of the Atlantic salmon IGF1 gene were sequenced, aligned and compared across individuals. Three SNPs were identified in the putative promoter (SNP1, g.5763G>T; GenBank no. AGKD01012745), intron 1 (SNP2, g.7292C>T; GenBank no. AGKD01012745) and intron 3 (SNP3, g.4671A>C; GenBank no. AGKD01133398) regions respectively. These SNPs were genotyped in a population of 4800 commercial Atlantic salmon with data on several weight and fillet traits measured at harvest (at approximately 3 years of age). In a mixed model, association analysis of individual SNPs, SNP1 and SNP3 were both significantly associated with several weight traits (P < 0.05). The estimated additive effect on overall harvest weight was approximately 35 and 110 g for SNPs 1 and 3 respectively. A haplotype analysis confirmed the association between genetic variation in the IGF1 gene with overall body weight (P < 0.05) and fillet component traits (P < 0.05). Our findings suggest the identified nucleotide polymorphisms of the IGF1 gene may either affect farmed Atlantic salmon growth directly or be in population‐wide linkage disequilibrium with causal variation, highlighting their possible utility as candidates for marker‐assisted selection in the aquaculture industry.
Interferon regulatory factor 3 as key element of the interferon signature in plasmacytoid dendritic cells from systemic lupus erythematosus patients: novel genetic associations in the Mexican mestizo population
Authors: Santana-de Anda K , Gómez-Martín D , Monsivais-Urenda A E , Salgado-Bustamante M , González-Amaro R , Alcocer-Varela J
Published: August 2014

Many genetic studies have found an association between interferon regulatory factors (IRF) single nucleotide polymorphisms (SNPs) and systemic lupus erythematosus (SLE); however, specific dendritic cell (DC) alterations have not been assessed. The aim of the present study was to address the expression of IRF3 and IRF5 on different DC subsets from SLE patients, as well as their association with interferon (IFN)-α production and novel SNPs. For the genetic association analyses, 156 SLE patients and 272 healthy controls from the Mexican mestizo population were included. From these, 36 patients and 36 controls were included for functional analysis. Two IRF3 SNPs − rs2304206 and rs2304204 – were determined. We found an increased percentage of circulating pDC in SLE patients in comparison to controls (8·04 ± 1·48 versus 3·35 ± 0·8, P = 0·032). We also observed enhanced expression of IRF3 (64 ± 6·36 versus 36·1 ± 5·57, P = 0·004) and IRF5 (40 ± 5·25 versus 22·5 ± 2·6%, P = 0·010) restricted to this circulating pDC subset from SLE patients versus healthy controls. This finding was associated with higher IFN-α serum levels in SLE (160·2 ± 21 versus 106·1 ± 14 pg/ml, P = 0·036). Moreover, the IRF3 rs2304206 polymorphism was associated with increased susceptibility to SLE [odds ratio (OR), 95% confidence interval (CI) = 2·401 (1·187–4·858), P = 0·021] as well as enhanced levels of serum type I IFN in SLE patients who were positive for dsDNA autoantibodies. The IRF3 rs2304204 GG and AG genotypes conferred decreased risk for SLE. Our findings suggest that the predominant IRF3 expression on circulating pDC is a key element for the increased IFN-α activation based on the interplay between the rs2304206 gene variant and the presence of dsDNA autoantibodies in Mexican mestizo SLE patients.
Rethinking antithyroid drugs in pregnancy
Authors: Napier C. , Pearce S.H.S.
Published: August 2014

Uncontrolled hyperthyroidism in pregnancy poses a risk to both mother and foetus, and the optimal treatment strategy in this setting remains elusive. Instigation of pharmacological therapy or an alternative intervention during pregnancy requires careful consideration, and the evidence that has underpinned our choice of antithyroid drug has not been robust. Recent research developments have prompted us to question our practice, and reconsider our approach to managing this patient group.
Role of the Nrf2 signaling system in health and disease
Authors: Hybertson B. M. , Gao B.
Published: August 2014

A key component of cytoprotective gene regulation is the transcription factor nuclear factor erythroid 2‐related factor 2 (Nrf2), also known as nuclear factor erythroid 2‐like 2, from the gene NFE2L2. Under normal conditions, Nrf2 in the cell is targeted for proteasomal degradation by its inhibitor Kelch‐like ECH‐associated inhibitor 1 (Keap1). When stimulated by oxidative stress, electrophiles, or kinase activation, conformational changes in the Nrf2‐Keap1 complex inhibit proteasomal degradation of Nrf2, facilitating an increase in the amount of Nrf2 that binds to antioxidant response element sequences in the promoter regions of a variety of antioxidant, detoxification, and metabolic control genes. Nrf2 activation is mostly associated with beneficial cytoprotective gene regulation, but it can also have deleterious effects. For example, gene mutations in some types of cancers can lead to constitutive activation of Nrf2 and give the tumor cells growth advantages and increased drug resistance. Because cases exist where Nrf2/Keap1/ARE signaling is either too low or too high, there is great interest in the development of both Nrf2 activators and Nrf2 inhibitors as the basis of new therapies.
Lysophosphatidic acid stimulates cell migration of satellite cells. A role for the sphingosine kinase/sphingosine 1‐phosphate axis
Authors: Cencetti Francesca , Bruno Gennaro , Blescia Sabrina , Bernacchioni Caterina , Bruni Paola , Donati Chiara
Published: August 2014

Regulation of the motility of skeletal muscle precursor cells, such as satellite cells, is critically important for their proper recruitment at the site of tissue damage, and ultimately for its correct repair. Here we show that lysophosphatidic acid (LPA), which is well‐recognized as a powerful bioactive agent, strongly stimulates cell migration of activated murine satellite cells. The biological effect exerted by LPA was found to be induced via activation of LPA1 and LPA3, being abolished by cell treatment with the antagonist Ki16425, and severely impaired by siRNA‐mediated down‐regulation of the two receptor isoforms. In contrast, silencing of LPA2 potentiated the stimulation of cell motility by LPA, suggesting that it is negatively coupled to cell migration. Pharmacological inhibition of both sphingosine kinase (SK) isoforms using VPC96047, or the selective blocking of SK1 using VPC96091, abolished cell responsiveness to LPA; in agreement, gene silencing of SK1 or SK2 significantly reduced the biological effect of LPA. Moreover, the LPA‐dependent stimulation of cell chemotaxis was found to be impaired by down‐regulation of the sphingosine 1‐phosphate (S1P) receptors S1P1 or S1P4 by specific siRNAs. In summary, the results obtained support the notion that the sphingosine kinase/sphingosine 1‐phosphate (SK/S1P) axis is critically involved in the mechanism by which LPA elicits its pro‐migratory action. This study provides compelling new information on the regulatory mechanisms of satellite cell motility, and reinforces the view that the SK/S1P signaling pathway plays a crucial role in the control of skeletal muscle precursor cell biology.
Development of a highly‐potent anti‐angiogenic VEGF8–109 heterodimer by directed blocking of its VEGFR‐2 binding site
Authors: Ghavamipour Fahimeh , Shahangian S. Shirin , Sajedi Reza H. , Arab S. Shahriar , Mansouri Kamran , Aghamaali Mahmoud Reza
Published: August 2014

Angiogenesis is a hallmark of various pathological conditions and is controlled by a variety of angiogenic factors. Blockade of vascular endothelial growth factor (VEGF) as the most pivotal stimulator of angiogenesis offers a promising therapeutic approach for some diseases, typically cancer. In the present study, a heterodimeric antagonistic VEGF was precisely designed based on structural information of recently‐crystallized VEGF/VEGF receptor‐2 (VEGFR‐2/fetal liver kinase 1/kinase domain region) complex. Directed blocking of kinase domain region occurs via substitution of a VEGF receptor binding site by two peptide segments in one pole, whereas the binding domain of the other pole of VEGF was intact. Candidate peptides for substitution were selected considering to some sequence and structural criteria. A reliable model of modified VEGF was built, refined using molecular dynamics simulation and docked with VEGFR‐2. Docking analysis revealed that binding affinity of mutant VEGF was notably diminished, corroborating our design. Heterodimeric VEGF was expressed, refolded and highly purified by two‐step affinity chromatography. Dimerization of this antagonist was confirmed using some analytical techniques. Spectroscopic studies assured us to obtain the heterodimeric form of VEGF. Some angiogenic in vitro assays such endothelial cell proliferation and tube formation indicated that this antagonist is not only strongly capable of inhibiting angiogenesis (half maximal inhibitory concentration of 33 and 24 ng·mL−1, respectively), but also showed the highest inhibitory effect compared to all other heterodimeric VEGF variants. The high anti‐angiogenic potency of this VEGF antagonist may allow its future use as an anti‐tumor agent.

Structured digital abstract

WT-VEGF and M-VEGF bind by comigration in sds page (View interaction).
Tactical Urbanism: The New Vernacular of the Creative City
Authors: Mould Oli
Published: August 2014

The recent infatuation of urban governance with the ideologies of creativity has led to many cities over the world being branded as ‘Creative Cities’. This policy drive has been problematised of late as a neoliberal agenda, which critics argue aids in the gentrification of cities. One reaction to this has been the proliferation of community‐orientated initiatives on a smaller scale that are (sometimes) conducted outside the official capacity of the city. So‐called Tactical Urbanism draws from such activity and therefore has become a popular movement for people who have a desire to change and reconfigure their city and do so without governmental involvement. Championed by the urbanist Mike Lydon, this paper charts how Tactical Urbanism has become a brand in itself, with the term being used by urban governments as a means of continuing neoliberal policies of urban development in a post‐2008 recessionary era. This paper will show how Tactical Urbanism is defenestrating the former, in favour of the latter. In so doing, it is fast becoming the latest political vernacular of the Creative City.
Reactivity of cosmetic UV filters towards skin proteins: Model studies with Boc‐lysine, Boc‐Gly‐Phe‐Gly‐Lys‐OH, BSA and gelatin
Authors: Stiefel C. , Schwack W.
Published: August 2014

Synopsis

Objective

Organic UV filters are used as active ingredients in most sunscreens and also in a variety of daily care products. Their good (photo) stability is of special interest to guarantee protective function and to prevent interactions with the human skin. Due to the mostly electrophilic character of the UV filters, reactions with nucleophilic protein moieties like lysine side chains are conceivable. Prior studies showed that the UV filters octocrylene (OCR), butyl methoxydibenzoylmethane (BM‐DBM), ethylhexyl salicylate (EHS), ethylhexyl methoxycinnamate (EHMC), benzophenone‐3 (BP‐3), ethylhexyl triazone (EHT) and dibenzoylmethane (DBM) were able to covalently bind to an HPTLC amino phase and the amino acid models ethanolamine and butylamine after slightly heating and/or radiation.

Methods

Boc‐protected lysine, the tetrapeptide Boc‐Gly‐Phe‐Gly‐Lys‐OH, bovine serum albumin (BSA) and porcine gelatin were used as more complex models to determine the reactivity of the mentioned UV filters towards skin proteins under thermal or UV irradiation conditions.

Results

After gentle heating at 37°C, benzophenone imines were identified as reaction products of BP‐3 and OCR with Boc‐lysine and the tetrapeptide, whereas DBM and BM‐DBM yielded enamines. For EHMC, a Michael‐type reaction occurred, which resulted in addition of Boc‐lysine or the tetrapeptide to the conjugated double bond. Ester aminolysis of EHS and EHT mainly afforded the corresponding amides. Reactions of the UV filters with BSA changed the UV spectrum of BSA, generally associated with an increase of the absorption strength in the UVA or UVB range. For all protein models, the UV filters showed an increasing reactivity in the order EHT < EHMC < EHS < BP‐3 < OCR < DBM < BM‐DBM.

Conclusion

Especially the UV absorbers BM‐DBM, OCR and BP‐3, which are seen as common allergens or photoallergens, showed a high reactivity towards the different skin protein models. As the formation of protein adducts is recognized as important key element in the induction of skin sensitization, the results of this study can contribute to a better understanding of the underlying chemical mechanisms of such reactions.
Introduction: Rationale of the Symposium
Authors: Blauberger Michael , Puntscher Riekmann Sonja , Wydra Doris
Published: August 2014

This symposium item belongs to a section headed: SYMPOSIUM: CONVENTIONAL WISDOMS UNDER CHALLENGE – REVIEWING THE EU’S DEMOCRATIC DEFICIT IN TIMES OF CRISIS, which also includes Integration without Representation? The European Parliament and the Reform of Economic Governance in the EU by Berthold Rittberger (DOI: 10.1111/jcms.12185), Parliaments in the Euro Crisis: Can the Losers of Integration Still Fight Back? by Katrin Auel and Oliver Höing (DOI: 10.1111/jcms.12186), ‘European Elections are Second‐Order Elections’: Is Received Wisdom Changing? by Richard Corbett (DOI: 10.1111/jcms.12187), From ‘Sleeping Giant’ to Left–Right Politicization? National Party Competition on the EU and the Euro Crisis by Eric Miklin (DOI: 10.1111/jcms.12188), No Demos? Identities and Public Spheres in the Euro Crisis by Thomas Risse (DOI: 10.1111/jcms.12189), From Regulatory State to a Democratic Default by Giandomenico Majone (DOI: 10.1111/jcms.12190)
The validation of the 2010 American Association for the Study of Liver Diseases guideline for the diagnosis of hepatocellular carcinoma in an endemic area
Authors: Lin Ming‐Tsung , Chang Kuo‐Chin , Chou Yeh‐Pin , Tseng Po‐Lin , Yen Yi‐Hao , Wang Chih‐Chi , Tsai Ming‐Chao , Cheng Yu‐Fan , Eng Hock‐Liew , Wu Cheng‐Kung , Hu Tsung‐Hui
Published: August 2014

Background and Aim

Hepatocellular carcinoma (HCC) diagnosis could be made with one typical imaging study in a cirrhotic liver by the guideline of the American Association for the Study of Liver Diseases (AASLD) in 2010. Patients with hepatitis B who may not have fully developed cirrhosis could be applied. We aim to retrospectively analyze and validate the diagnostic power of the 2010 guideline in an HCC endemic area (Taiwan).

Methods

From January 2006 to December 2010, a total of 648 patients with liver tumor post‐surgical resection were reviewed. The fibrotic scores were verified by METAVIR score 4. Among the 648 patients, 569 (87.8%) were HCC patients. Hepatitis B accounts for 54.5%, hepatitis C 21.9%, hepatitis B + C 2.8%, and non‐hepatitis B or C 20.7% of patients. Two hundred eighty‐eight of 648 (44%) patients were with cirrhotic liver.

Results

The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy of the 2010 AASLD guideline f are 99.1%, 36.7%, 91.9%, 85.3%, and 91.5%, respectively. Cirrhotic liver exhibited a higher PPV (P < 0.001) but lower specificity (P = 0.0479) than non‐cirrhotic liver. In both cirrhotic and non‐cirrhotic condition, no difference existed in patients with hepatitis B or hepatitis C (P > 0.05).

Conclusions

Similar sensitivity of HCC diagnosis existed between cirrhotic and non‐cirrhotic liver, and across different fibrotic stages. But cirrhotic liver exhibited a higher PPV. Hepatitis B or C has no decisive effect in HCC diagnosis.
The ‘Nothing’ Trope: Self‐Worth in Renaissance Poetry
Authors: Archdeacon Anthony
Published: August 2014

The recurrence of ‘nothing’ as a topic in renaissance poetry has been explored by many critics, but little attention has been given to the particular trope which is the focus of this article: what might be called the ‘personal nothing’ trope. The article explores various possible interpretations of the trope and explanations for its appearance in English poetry at the end of the 16th century. With reference to poets such as John Donne and lesser known metaphysical poets such as John Davies of Hereford, links to contemporary theology, philosophy and medical writing are suggested, as well as to more particular biographical detail of the poets concerned. The article also considers how the trope relates to Marxist and New Historicist readings of the period. The article argues that the trope suggests something of the value systems and perhaps also the psychological states of the poets, who shared in common a privileged social status which was nevertheless dependent on patronage and preferment in the late Elizabethan and early Jacobean courts.
CONFINED QUEST FOR CONTINUITY: THE CATEGORICAL VERSUS CONTINUOUS NATURE OF ATTACHMENT
Authors: van IJzendoorn Marinus H. , Bakermans‐Kranenburg Marian J.
Published: August 2014

The use of the Adult Attachment Interview (AAI) in the NICHD Study of Early Child Care and Youth Development (NICHD SECCYD) is a major contribution to the field. The core of the current monograph pertains to psychometrics (dimensional vs. categorical assessment) of the AAI and continuity of attachment over time. We argue that the generalizability of the conclusions with regard to the AAI is limited to similar groups, because of the low‐risk adolescence nature of the sample, with concomitant underrepresentation of the preoccupied and unresolved classifications in the current sample (each only 3%). Baron von Münchhausen's paradox emerges in the use of the same source of coded data for categorical classifications and continuous scales of the AAI scoring procedure. At the same time, the monograph convincingly demonstrates that earned security cannot be assessed retrospectively in a valid and reliable manner, and the study highlights the power of scientific collaboration as realized in the NICHD SECCYD.
Quantitative Assessment of Human MRSA Risks from Swine
Authors: Cox Louis Anthony (Tony) , Popken Douglas A.
Published: August 2014

The public health community, news media, and members of the general public have expressed significant concern that methicillin‐resistant Staphylococcus aureus (MRSA) transmitted from pigs to humans may harm human health. Studies of the prevalence and dynamics of swine‐associated (ST398) MRSA have sampled MRSA at discrete points in the presumed causative chain leading from swine to human patients, including sampling bacteria from live pigs, retail meats, farm workers, and hospital patients. Nonzero prevalence is generally interpreted as indicating a potential human health hazard from MRSA infections, but quantitative assessments of resulting risks are not usually provided. This article integrates available data from several sources to construct a conservative (plausible upper bound) probability estimate for the actual human health harm (MRSA infections and fatalities) arising from ST398‐MRSA from pigs. The model provides plausible upper bounds of approximately one excess human infection per year among all U.S. pig farm workers, and one human infection per 31 years among the remaining total population of the United States. These results assume the possibility of transmission events not yet observed, so additional data collection may reduce these estimates further.
Political Violence, Interstate Rivalry, and the Diffusion of Public Health Crises
Authors: Reeder Bryce W. , Reeder Matthew R.
Published: August 2014

Objective

The objectives of the study were to expand the literature on political violence and public health by exploring the possibility that the public health consequences of civil war not only apply to the host country, but also diffuse across international borders. We discuss and empirically test a diffusion mechanism absent from the literature in this area—the incentive of a proximate state to reallocate resources in response to intrastate violence and the presence of interstate rivalry.

Methods

Our hypotheses were tested using a directed dyad research design that included all politically relevant dyads from 1997 to 2001. We used fixed‐effects panel regression to estimate the influence of proximate intrastate violence and interstate rivalry on changes in infant mortality rate (IMR).

Results

Our results indicated that proximate intrastate violence and interstate rivalry are associated with increases in IMR. In addition, the influence of proximate intrastate violence on IMR increases as the severity of the conflict increases.

Conclusion

The public health consequences of civil war do diffuse across international borders, especially in cases in which interstate rivalry was present and the political violence in a proximate state was severe.
Computing Galois representations of modular abelian surfaces
Authors: Zeng Jinxiang
Published: August 2014

Let $\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}f\in S_2(\Gamma _0(N))$ be a normalized newform such that the abelian variety $A_f$ attached by Shimura to $f$ is the Jacobian of a genus-two curve. We give an efficient algorithm for computing Galois representations associated to such newforms.
A census of quadratic post-critically finite rational functions defined over
Authors: Lukas David , Manes Michelle , Yap Diane
Published: August 2014

We find all quadratic post-critically finite (PCF) rational functions defined over $\mathbb{Q}$, up to conjugation by elements of $\mathop{\rm PGL}_2(\overline{\mathbb{Q}})$. We describe an algorithm to search for possibly PCF functions. Using the algorithm, we eliminate all but 12 rational functions, all of which are verified to be PCF. We also give a complete description of all possible rational preperiodic structures for quadratic PCF functions defined over $\mathbb{Q}$.
Nonvanishing of twists of -functions attached to Hilbert modular forms
Authors: Ryan Nathan C. , Tornaría Gonzalo , Voight John
Published: August 2014

We describe algorithms for computing central values of twists of $L$-functions associated to Hilbert modular forms, carry out such computations for a number of examples, and compare the results of these computations to some heuristics and predictions from random matrix theory.
Tracking -adic precision
Authors: Caruso Xavier , Roe David , Vaccon Tristan
Published: August 2014

We present a new method to propagate $p$-adic precision in computations, which also applies to other ultrametric fields. We illustrate it with some examples and give a toy application to the stable computation of the SOMOS 4 sequence.
Time-dependent dielectric breakdown measurements of porous organosilicate glass using mercury and solid metal probes
Authors: Pei Dongfei , Nichols Michael T. , King Sean W. , Clarke James S. , Nishi Yoshio , Shohet J. Leon
Published: August 2014

Time-dependent dielectric breakdown (TDDB) is one of the major concerns for low-k dielectric materials. During plasma processing, low-k dielectrics are subjected to vacuum ultraviolet photon radiation and charged-particle bombardment. To examine the change of TDDB properties, time-to-breakdown measurements are made to porous SiCOH before and after plasma exposure. Significant discrepancies between mercury and solid-metal probes are observed and have been shown to be attributed to mercury diffusion into the dielectric porosities.
Measurement and modeling of binaural loudness summation for hearing-impaired listeners
Authors: Moore Brian C. J. , Gibbs Alexander , Onions Grace , Glasberg Brian R.
Published: August 2014

The summation of loudness across ears is often studied by measuring the level difference required for equal loudness (LDEL) of monaural and diotic sounds. Typically, the LDEL is ∼5–6 dB, consistent with the idea that a diotic sound is ∼1.5 times as loud as the same sound presented monaurally at the same level, as predicted by the loudness model of Moore and Glasberg [J. Acoust. Soc. Am. 121, 1604–1612 (2007)]. One might expect that the LDEL would be <5–6 dB for hearing-impaired listeners, because loudness recruitment leads to a more rapid change of loudness for a given change in level. However, previous data sometimes showed similar LDEL values for normal-hearing and hearing-impaired listeners. Here, the LDEL was measured for hearing-impaired listeners using narrowband and broadband noises centered at 500 Hz, where audiometric thresholds were near-normal, and at 3000 or 4000 Hz, where audiometric thresholds were elevated. The mean LDEL was 5.6 dB at 500 Hz and 4.2 dB at the higher center frequencies. The results were predicted reasonably well by an extension of the loudness model of Moore and Glasberg.
Identification of a Novel 6′-
N
-Aminoglycoside Acetyltransferase, AAC(6′)-Iak, from a Multidrug-Resistant Clinical Isolate of Stenotrophomonas maltophilia
Authors: Tada Tatsuya , Miyoshi-Akiyama Tohru , Dahal Rajan K. , Mishra Shyam K. , Shimada Kayo , Ohara Hiroshi , Kirikae Teruo , Pokhrel Bharat M.
Published: August 2014

Stenotrophomonas maltophilia
IOMTU250 has a novel 6′-
N
-aminoglycoside acetyltransferase-encoding gene,
aac(6
′
)-Iak
. The encoded protein, AAC(6′)-Iak, consists of 153 amino acids and has 86.3% identity to AAC(6′)-Iz.
Escherichia coli
transformed with a plasmid containing
aac(6
′
)-Iak
exhibited decreased susceptibility to arbekacin, dibekacin, neomycin, netilmicin, sisomicin, and tobramycin. Thin-layer chromatography showed that AAC(6′)-Iak acetylated amikacin, arbekacin, dibekacin, isepamicin, kanamycin, neomycin, netilmicin, sisomicin, and tobramycin but not apramycin, gentamicin, or lividomycin.
NDM-12, a Novel New Delhi Metallo-β-Lactamase Variant from a Carbapenem-Resistant Escherichia coli Clinical Isolate in Nepal
Authors: Tada Tatsuya , Shrestha Basudha , Miyoshi-Akiyama Tohru , Shimada Kayo , Ohara Hiroshi , Kirikae Teruo , Pokhrel Bharat M.
Published: August 2014

A novel New Delhi metallo-β-lactamase variant, NDM-12, was identified in a carbapenem-resistant
Escherichia coli
clinical isolate obtained from a urine sample from a patient in Nepal. NDM-12 differed from NDM-1 by two amino acid substitutions (M154L and G222D). The enzymatic activities of NDM-12 against β-lactams were similar to those of NDM-1, although NDM-12 showed lower
k
cat
/

K
m

ratios for all β-lactams tested except doripenem. The
bla
NDM-12
gene was located in a plasmid of 160 kb.
An unusual cause of altered mental status: the importance of monitoring a patient's blood pressure
Authors: Mathew Jacob , Koo Matthew , Crook Irina R , Jahanmir Jay
Published: August 2014

A 73-year-old man presented to the emergency room for acute onset altered mental status. The initial work-up yielded no definitive cause. An MRI demonstrated lesions in the bilateral posterior occipital lobes (not noted on an earlier MRI obtained from an outside institution) that were suggestive of posterior reversible encephalopathy syndrome (PRES). He had a history of Parkinson's disease complicated by autonomic instability (wide blood pressure fluctuations) that was medically controlled in the outpatient setting. During the early course of his hospitalisation, he again displayed wide blood pressure fluctuations. After his blood pressure stabilised, his mental status eventually improved to baseline. A repeat MRI obtained demonstrated near-complete resolution of the previously noted lesions and confirmed the diagnosis of PRES.