bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemodetection in fluctuating environments: Receptor coupling, buffering, and antagonism
Authors: Lalanne Jean-Benoît , François Paul
Published: January 2015

Significance

Cells have to reliably process biochemical signals in the presence of many different sources of information. For instance, immune cells have to discriminate foreign peptides from many potentially similar self-peptides, which sometimes lead to the absence of active decision even in the presence of infection (a process called antagonism). In this article, we mathematically formalize this chemodetection problem. By contrasting two types of models for ligand detection (independent or coupled receptors) we show that if environmental noise is not statistically negligible (e.g., “long-tailed”), antagonism can be advantageous to buffer undesirable fluctuations in environmental composition.
Metabolic theory predicts whole-ecosystem properties
Authors: Schramski John R. , Dell Anthony I. , Grady John M. , Sibly Richard M. , Brown James H.
Published: January 2015

Significance

A theory is presented which shows how the metabolism of individual organisms controls the flow of carbon through ecosystems. The theory synthesizes top-down, ecosystem-level and bottom-up, organism-level approaches to ecological energetics and material cycles. The theory predicts a very simple straight-line relationship between residence time of carbon molecules and the ratio of whole-ecosystem biomass to primary productivity. This and additional predictions for total throughfow and recycling are supported by numerical models and data from real ecosystems. The theory provides a powerful way to understand the roles of organisms in ecosystem processes at scales from local habitats to the biosphere. Such an understanding is important for addressing the impacts of human-caused changes in climate, land use, and biodiversity.
Mitophagy confers resistance to siderophore-mediated killing by
Pseudomonas aeruginosa
Authors: Kirienko Natalia V. , Ausubel Frederick M. , Ruvkun Gary
Published: January 2015

Significance

Pathogens express virulence factors to support their growth and reproduction while hosts activate various immune processes to promote pathogen clearance and minimize damage. In this study, we establish a new role for pyoverdin, an iron-binding siderophore produced by the bacterium
Pseudomonas aeruginosa
. In addition to promoting growth by acquiring iron, pyoverdin serves as a secreted bacterial toxin that disrupts mitochondria and iron homeostasis in
Caenorhabditis elegans
. We show that exposure to pyoverdin triggers mitochondrial damage and subsequent mitophagy (lysosomal degradation of damaged mitochondria). Importantly, mitophagy confers a protective effect against exposure to either pyoverdin or to a synthetic iron chelator, demonstrating a function for mitophagy in innate immunity. Finally, we show that iron chelation causes mitophagy in mammalian cells.
Kontiguität und Similarität der poetischen Sprache der Antike
Authors: Rasche Michael
Published: January 2015

Cassirer proclaimed the human as ‘animal symbolicum’. Language, art and religion are manifestations of an symbolic and symbol-creating awareness. The symbols are caused by a movement which is to be characterized as tropical. A symbol can be generated as a metonymic term, based on the principle of contiguity, but also as an metaphoric term, corresponding to the principle of similarity. The perception of these tropical movements draws the attention to the origination of a symbolic term as well as to the changes of already existing terms. The history of the ancient symbolic speech is a history of permanent creations, but also of mutations of meaning. This history is noticeable in Greece for the first time in Homer. His figurative speech is influenced by the mythical contiguity, which yields to a metaphorization and allegorization of the symbols in lyrics and philosophy in the following period, but still remains present in the religious literature. Finally, the symbolic speech of the new Christianity is situated in the non-solvable tension between the principles of contiguity and similarity. A recognition of this history of the ancient symbolic speech is required for its subsequent analysis, which is especially important for Christianity, for whom the ancient symbolism is normative, as well as for the philosophy, which desires to recognize its own history.
Zwei Stimmen aus der Renaissancedebatte um die Person Ciceros
Authors: Gawlick Günter
Published: January 2015

In his essay the author draws attention to two 16th century humanists who engaged in the debate on Cicero the Man (as distinguished from Cicero the Orator, or Cicero the Philosopher).
In 1534, Ortensio Lando (1519–1552), a man of letters, published Cicero relegatus & Cicero revocatus, which was a collection of objections to Cicero’s character and habits brought forward in an imaginary conversation, as well as of arguments in his defence proposed in an equally fictitious public hearing, thus producing an apparent equilibrium. Lando, however, did not leave us guessing about his meaning, but gave us hints about his own attitude to Cicero.
In 1537, Sebastiano Corrado (1512–1556), an editor and commentator of various Ciceronian writings, published In M. T. Ciceronem Quaestura, a collection of textual emendations to his œuvres. In order to make it more attractive reading, he wrote it in dialogue form and called the readings he approved of, ‘gold coins’, those he rejected, ‘false coins’, thus building a stock of allegedly reliable readings.
The coin metaphor recurred in Corrado’s Egnatius, sive Quaestura (1555) which was an attempt to lay, in form of dialogue, the foundations of a reliable biography of Cicero. Here three scholars discuss all the information provided by Cicero himself, his contemporaries and later sources on his life and work. Information they approve of is treasured as gold coin, the rest is rejected as false coin. It turns out, however, that Corrado was strongly prejudiced against Greek sources shedding an unfavourable light on Cicero. The result was an apology rather than a biography of Cicero.
On the subject of subject in Finnish
Authors: Huumo Tuomas , Helasvuo Marja-Liisa
Published: January 2015

This article examines the category of subject in Finnish. Among the grammatical
features examined are case marking, agreement and syntax, semantic role,
its relation to other sentence elements and its semantic function as regards the
sentence as a whole. One important discourse feature is whether the subject
introduces a referent and whether that referent is mentioned again later in the
discourse. We discuss different construction types and examine whether the
alleged subjects fulfil the role of the subject as defined in cognitive grammar,
i.e. which function as a clause-level trajector and as a starting point for the
construal of the relationship and its participants. More generally, it is argued
that the trajector does not necessarily constitute the subject of the clause-level
construction. The function of an e-NP (existential NP) is proposed for such
elements instead.
Hidden subjects in conversation
Authors: Pajusalu Renate
Published: January 2015

The chapter deals with implicit unspecific group referents introduced by verb
forms (the conditional and the impersonal) which lack person marking. They
have different contexts of use: the personless conditional is preferred when the
aim of the conversation is to plan a future activity, while the existential impersonal
is first and foremost used in narratives. The personless conditional is typically
inclusive, incorporating one or both of the interlocutors into the group.
The impersonal is typically speaker-exclusive and refers to a group that does not
include the participants of the conversation. For the analysis, the data from the
Corpus of Spoken Estonian (University of Tartu) are used.
Subjects under generic conditions
Authors: Jokela Hanna , Plado Helen
Published: January 2015

The chapter discusses implied subjects creating open or generic reference in
Finnish and Estonian if-clauses from a contrastive perspective. We focus on the
so-called zero person constructions, passives/impersonals, and the Estonian
da-infinitive which acts as a predicate of an if-clause. These construction types
lack subject; in addition they can create open or generic reference. The constructions
are closely interrelated; however, each of them has some restrictions in use
and differences in interpretation. The passive in Finnish and the impersonal in
Estonian if-clauses have a tendency to refer to a group, whereas the zero person
and Estonian da-infinitive refer to one individual. The interpretation of implied
subject depends on the conditional clause type, the context, and the verb form
that is used.
The world is raining
Authors: Eriksen Pål Kristian , Kittilä Seppo , Kolehmainen Leena
Published: January 2015

The peculiar semantic properties of meteorological predicates have linguistic
consequences. Some of these consequences concern their subjects, which do not
behave like prototypical subjects do. Meteorological predicates often lack a subject,
and in the languages where they do have subjects they are non-referential,
non-topical, indefinite, inanimate or non-agentive entities. They are typically
either expletive elements or lexical elements referring to the spatial, temporal
or atmospheric background, i.e. elements which would otherwise have been
encoded as adverbial phrases. Although the nominative – or some other kind of
zero marking – and default agreement marking (3rd person, singular number,
neuter gender) are typical of these subjects, the study argues that they display
special behavior which distinguishes them from canonical cases.
The role of non-canonical subjects in the overall grammar of a language
Authors: Janda Laura A. , Divjak Dagmar
Published: January 2015

We offer a model of Russian core syntax in terms of a radial category network
of constructions. The prototype corresponds to Langacker’s “canonical event
model”, namely a prototypical transitive event, and more peripheral constructions
are related to it via metaphor and metonymy. From this perspective we
focus on non-canonical subjects marked in the dative case, highlighting the
complex interaction of lexical items (verbs) with constructions, and building
on our previous work on case and infinitives. We hypothesize that a speaker’s
perception of cause may be influenced by the use of non-canonical subjects
(in Russian) rather than canonical subjects (in English) and present the results
of an experiment. We are unable to prove any conclusive effect, but show the
importance and need for further testing.
Iconicity of logic - and the roots of "iconicity" concept
Authors: Stjernfelt Frederik
Published: January 2015

It seems to be a standard assumption that Charles Morris originated the concept of “iconicity” on the basis of Peirce’s icon-index-symbol discussion. This paper locates the origin in Peirce himself, in the context of judging the merits of different mathematical and logic representations – the more iconic such representations generally being preferable to less iconic ones, for scientific purposes. In Peirce’s Collected Papers, “iconicity” occurs in the discussion of different conventions in the logic representation system called “Existential Graphs”. This paper provides the context of logic representations in order to show how Peirce’s articulation of the concept of “iconicity” comes out of the attempt to find as iconic a way as possible to depict logical relations. Moreover, this indicates a use of “iconicity”, from the very beginning, which addresses not only similarities between different visual representations – but also visual representations of abstract contents.
Phonemes as images
Authors: Nobile Luca
Published: January 2015

This paper attempts to improve the understanding of shape-sound symbolism by isolating the phonological features of the pseudo-words used in the experiments and the graphic features of the figures matched with them. In a first section, it analyses the classic maluma-takete effect from both an articulatory and acoustical point of view, showing that it is determined by several phonological features operating simultaneously. In a second section, two new experiments are presented to isolate, first, vowels and consonants and, second, the consonant features of [voicing], [manner of articulation], [nasality] and [place of articulation] in relation to the graphic features of {acuity}, {continuity}, {curvature}, {regularity}, and {density}. The main result is that each phonological feature shows a different pattern of correlations with the graphic features, determined by its subtle phono-articulatory and phono-acoustic structure.
Rethinking diagrammatic iconicity from an evolutionary perspective
Authors: Ohori Toshio
Published: January 2015

This paper reexamines the notion of diagrammatic iconicity in grammar, i.e. the isomorphism of relational structure across form and meaning. After a quick survey of the various definitions of diagrammatic iconicity, some illustrations are given from coordinating constructions. It is shown that grammatical (a)symmetry in the expression of complex events corresponds to conceptual (a)symmetry. Next, diagrammatic iconicity is examined from an evolutionary viewpoint. Based on two considerations, namely, (i) that diagrammatic iconicity in grammar presupposes the bifurcation of form and meaning, and (ii) that analogical mapping between linguistic form and cognitive experience is a product of highly evolved cognitive capacity, it is claimed that diagrammatic iconicity is by no means “primitive” but a crucial species-specific trait of human language.
Computational assessment of text readability
Authors: Collins-Thompson Kevyn
Published: January 2015

Assessing text readability is a time-honored problem that has even more relevance in today’s information-rich world. This article provides background on how readability of texts is assessed automatically, reviews the current state-of-the-art algorithms in automatic modeling and predicting the reading difficulty of texts, and proposes new challenges and opportunities for future exploration not well-covered by current computational research.
Associative lexical cohesion as a factor in text complexity
Authors: Flor Michael , Klebanov Beata Beigman
Published: January 2015

In this paper we present an application of associative lexical cohesion to the analysis of text complexity as determined by expert-assigned US school grade levels. Lexical cohesion in a text is represented as a distribution of pairwise positive normalized mutual information values. Our quantitative measure of lexical cohesion is Lexical Tightness (LT), computed as average of such values per text. It represents the degree to which a text tends to use words that are highly inter-associated in the language. LT is inversely correlated with grade levels and adds significantly to the amount of explained variance when estimating grade level with a readability formula. In general, simpler texts are more lexically cohesive and complex texts are less cohesive. We further demonstrate that lexical tightness is a very robust measure. We compute lexical tightness for a whole text and also across segmental units of a text. While texts are more cohesive at the sentence level than at the paragraph or whole-text levels, the same systematic variation of lexical tightness with grade level is observed for all levels of segmentation. Measuring text cohesion at various levels uncovers a specific genre effect: informational texts are significantly more cohesive than literary texts, across all grade levels.
Making numerical information more accessible
Authors: Bautista Susana , Saggion Horacio
Published: January 2015

Are rounded numbers easier to understand than exact numbers? Information in newspapers often takes the form of numerical expressions which pose comprehension problems for many people, including people with disabilities, low literacy levels or lack of access to advanced technology. The purpose of this paper is to motivate and describe a rule-based lexical component that simplifies numerical expressions in Spanish texts. We propose a simplification approach that makes news articles more accessible to readers with specials needs by rewriting difficult numerical expressions in a simpler way. We carried out a study that identifies powerful simplification strategies to simplify numerical information in a text by analysing a parallel corpus of original texts and their manual simplifications. The study is complemented with an analysis of simplifications obtained in response to a questionnaire where subjects were asked to produce simplifications of numerical expressions in context. Finally, we implemented and evaluated a simplification system that mimics the simplification strategies that were found to be effective.
Words that go together
Authors: Dąbrowska Ewa
Published: January 2015

Although formulaic language has been studied extensively from both a linguistic and psycholinguistic perspective, little is known about the relationship between individual speakers’ knowledge of collocations and their linguistic experience, or between collocational knowledge and other aspects of linguistic knowledge. This is partly because work in these areas has been hampered by lack of an adequate instrument measuring speakers’ knowledge of collocations. This paper describes the development of such an instrument, the “Words that go together” (WGT) test, and some preliminary research using it. The instrument is a multiple choice test consisting of 40 items of varying frequency and collocation strength. The test was validated with a sample of 80 adult native speakers of English. Test-retest reliability was 0.80 and split-half reliability was 0.88. Convergent validity was established by comparing participants’ scores with measures expected to correlate with language experience (print exposure, education, and age) and other linguistic abilities (vocabulary size, grammatical comprehension); divergent validity was established by comparing test scores with nonverbal IQ. The results of the validation study are then used to compare speakers’ performance on the WGT with corpus-based measures of collocation strength (mutual information, z-score, t-score and simple frequency); however, no statistically reliable relationships were found.
N-gram probability effects in a cloze task
Authors: Shaoul Cyrus , Harald Baayen R. , Westbury Chris F.
Published: January 2015

What knowledge influences our choice of words when we write or speak? Predicting which word a person will produce next is not easy, even when the linguistic context is known. One task that has been used to assess context dependent word choice is the fill-in-the-blank task, also called the cloze task. The cloze probability of specific context is an empirical measure found by asking many people to fill in the blank. In this paper we harness the power of large corpora to look at the influence of corpus-derived probabilistic information from a word’s micro-context on word choice. We asked young adults to complete short phrases called n-grams with up to 20 responses per phrase. The probability of the responded word and the conditional probability of the response given the context were predictive of the frequency with which each response was produced. Furthermore the order in which the participants generated multiple completions of the same context was predicted by the conditional probability as well. These results suggest that word choice in cloze tasks taps into implicit knowledge of a person’s past experience with that word in various contexts. Furthermore, the importance of n-gram conditional probabilities in our analysis is further evidence of implicit knowledge about multi-word sequences and support theories of language processing that involve anticipating or predicting based on context.
Trial-by-trial adjustments in control triggered by incidentally encoded semantic cues
Authors: Blais Chris , Harris Michael B. , Sinanian Michael H. , Bunge Silvia A.
Published: January 2015

Cognitive control mechanisms provide the flexibility to rapidly adapt to contextual demands. These contexts can be defined by top-down goals—but also by bottom-up perceptual factors, such as the location at which a visual stimulus appears. There are now several experiments reporting contextual control effects. Such experiments establish that contexts defined by low-level perceptual cues such as the location of a visual stimulus can lead to context-specific control, suggesting a relatively early focus for cognitive control. The current set of experiments involved a word–word interference task designed to assess whether a high-level cue, the semantic category to which a word belongs, can also facilitate contextual control. Indeed, participants exhibit a larger Flanker effect to items pertaining to a semantic category in which 75% of stimuli are incongruent than in response to items pertaining to a category in which 25% of stimuli are incongruent. Thus, both low-level and high-level stimulus features can affect the bottom-up engagement of cognitive control. The implications for current models of cognitive control are discussed.
The role of lexical variables in the visual recognition of Chinese characters: A megastudy analysis
Authors: Sze Wei Ping , Yap Melvin J. , Rickard Liow Susan J.
Published: January 2015

Logographic Chinese orthography partially represents both phonology and semantics. By capturing the online processing of a large pool of Chinese characters, we were able to examine the relative salience of specific lexical variables when this nonalphabetic script is read. Using a sample of native mainland Chinese speakers ( N = 35), lexical decision latencies for 1560 single characters were collated into a database, before the effects of a comprehensive range of variables were explored. Hierarchical regression analyses determined the unique item-level variance explained by orthographic (frequency, stroke count), semantic (age of learning, imageability, number of meanings), and phonological (consistency, phonological frequency) factors. Orthographic and semantic variables, respectively, accounted for more collective variance than the phonological variables. Significant main effects were further observed for the individual orthographic and semantic predictors. These results are consistent with the idea that skilled readers tend to rely on orthographic and semantic information when processing visually presented characters. This megastudy approach marks an important extension to existing work on Chinese character recognition, which hitherto has relied on factorial designs. Collectively, the findings reported here represent a useful set of empirical constraints for future computational models of character recognition.
Unipotent,Atoh1+ progenitors maintain the Merkel cell population in embryonic and adult mice
Authors: Wright Margaret C. , Reed-Geaghan Erin G. , Bolock Alexa M. , Fujiyama Tomoyuki , Hoshino Mikio , Maricich Stephen M.
Published: January 2015

Resident progenitor cells in mammalian skin generate new cells as a part of tissue homeostasis. We sought to identify the progenitors of Merkel cells, a unique skin cell type that plays critical roles in mechanosensation. We found that some Atoh1-expressing cells in the hairy skin and whisker follicles are mitotically active at embryonic and postnatal ages. Genetic fate-mapping revealed that these Atoh1-expressing cells give rise solely to Merkel cells. Furthermore, selective ablation of Atoh1+ skin cells in adult mice led to a permanent reduction in Merkel cell numbers, demonstrating that other stem cell populations are incapable of producing Merkel cells. These data identify a novel, unipotent progenitor population in the skin that gives rise to Merkel cells both during development and adulthood.
Ror2 regulates branching, differentiation, and actin-cytoskeletal dynamics within the mammary epithelium
Authors: Roarty Kevin , Shore Amy N. , Creighton Chad J. , Rosen Jeffrey M.
Published: January 2015

Wnt signaling encompasses β-catenin–dependent and –independent networks. How receptor context provides Wnt specificity in vivo to assimilate multiple concurrent Wnt inputs throughout development remains unclear. Here, we identified a refined expression pattern of Wnt/receptor combinations associated with the Wnt/β-catenin–independent pathway in mammary epithelial subpopulations. Moreover, we elucidated the function of the alternative Wnt receptor Ror2 in mammary development and provided evidence for coordination of this pathway with Wnt/β-catenin–dependent signaling in the mammary epithelium. Lentiviral short hairpin RNA (shRNA)-mediated depletion of Ror2 in vivo increased branching and altered the differentiation of the mammary epithelium. Microarray analyses identified distinct gene level alterations within the epithelial compartments in the absence of Ror2, with marked changes observed in genes associated with the actin cytoskeleton. Modeling of branching morphogenesis in vitro defined specific defects in cytoskeletal dynamics accompanied by Rho pathway alterations downstream of Ror2 loss. The current study presents a model of Wnt signaling coordination in vivo and assigns an important role for Ror2 in mammary development.
A Ror recruit to mammary gland development
Authors: Short Ben
Published: January 2015

Study shows how noncanonical Wnt signaling promotes differentiation and morphogenesis of mammary epithelia.
Gating pore currents are defects in common with two Nav1.5 mutations in patients with mixed arrhythmias and dilated cardiomyopathy
Authors: Moreau Adrien , Gosselin-Badaroudine Pascal , Delemotte Lucie , Klein Michael L. , Chahine Mohamed
Published: January 2015

The gating pore current, also called omega current, consists of a cation leak through the typically nonconductive voltage-sensor domain (VSD) of voltage-gated ion channels. Although the study of gating pore currents has refined our knowledge of the structure and the function of voltage-gated ion channels, their implication in cardiac disorders has not been established. Two Nav1.5 mutations (R222Q and R225W) located in the VSD are associated with atypical clinical phenotypes involving complex arrhythmias and dilated cardiomyopathy. Using the patch-clamp technique, in silico mutagenesis, and molecular dynamic simulations, we tested the hypothesis that these two mutations may generate gating pore currents, potentially accounting for their clinical phenotypes. Our findings suggest that the gating pore current generated by the R222Q and R225W mutations could constitute the underlying pathological mechanism that links Nav1.5 VSD mutations with human cardiac arrhythmias and dilatation of cardiac chambers.
Topological conformal dimension
Authors: DiMarco Claudio
Published: January 2015

We investigate a quasisymmetrically invariant counterpart of the topological Hausdorff dimension of a metric space. This invariant, called the topological conformal dimension, gives a lower bound on the topological Hausdorff dimension of quasisymmetric images of the space. We obtain results concerning the behavior of this quantity under products and unions, and compute it for some classical fractals. The range of possible values of the topological conformal dimension is also considered, and we show that this quantity can be fractional.
ENVIRONMENTS and EOL: identification of Environment Ontology terms in text and the annotation of the Encyclopedia of Life
Authors: Pafilis Evangelos , Frankild Sune P. , Schnetzer Julia , Fanini Lucia , Faulwetter Sarah , Pavloudi Christina , Vasileiadou Katerina , Leary Patrick , Hammock Jennifer , Schulz Katja , Parr Cynthia Sims , Arvanitidis Christos , Jensen Lars Juhl
Published: January 2015

Summary: The association of organisms to their environments is a key issue in exploring biodiversity patterns. This knowledge has traditionally been scattered, but textual descriptions of taxa and their habitats are now being consolidated in centralized resources. However, structured annotations are needed to facilitate large-scale analyses. Therefore, we developed ENVIRONMENTS, a fast dictionary-based tagger capable of identifying Environment Ontology (ENVO) terms in text. We evaluate the accuracy of the tagger on a new manually curated corpus of 600 Encyclopedia of Life (EOL) species pages. We use the tagger to associate taxa with environments by tagging EOL text content monthly, and integrate the results into the EOL to disseminate them to a broad audience of users.

Availability and implementation: The software and the corpus are available under the open-source BSD and the CC-BY-NC-SA 3.0 licenses, respectively, at http://environments.hcmr.gr

Contact:  pafilis@hcmr.gr or lars.juhl.jensen@cpr.ku.dk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Dural Sinus (Cerebral Venous) Thrombosis in a Pediatric Trauma Patient
Authors: Wilcher Jonathan , Pannell Michelle
Published: January 2015

Objective

Closed head injury rarely predisposes patients, particularly children, to the development of dural sinus thrombosis. In addition, most cases of sinus thrombosis are subacute in nature. The following is a case report of a precipitous course of dural sinus thrombosis after closed head injury in a pediatric trauma patient.

Description

A 14-year-old African American girl presented to the emergency department as a trauma activation. She was an unrestrained rear-seat passenger involved in a motor vehicle collision during which she was ejected. She experienced loss of consciousness and was found unresponsive at the scene. She was intubated and then transported via helicopter to the level I trauma center. Initial head computed tomography (CT) revealed no acute intracranial abnormality. The head CT was repeated 15 hours later when nursing noted the patient to be acutely hypertensive and tachycardic with an 8-mm nonreactive right pupil. The repeated CT showed interval development of extensive dural sinus thrombosis, cerebellar edema and infarct, as well as mild downward transtentorial herniation. Because of multiple coexistent injuries and complications, treatment of the dural sinus thrombosis was difficult. The hospital course was complicated and there was very little improvement in the patient's condition.

Conclusions

The multisystem injured trauma patient poses many clinical challenges. Treatment of dural sinus thrombosis is difficult and controversial and requires an investigation into possible risk factors for a hypercoagulable state. Clinical outcomes vary from excellent to dismal.
Physical sciences at Diamond: past achievements and future opportunities
Authors: McMorrow D. F.
Published: January 2015

The start of user operation at the Diamond Light Source in January 2007 marks a major milestone for the physical sciences in the UK. The routine delivery to the UK community of ultra-bright X-ray beams from the third-generation source has provided us with capabilities that were available previously only at international sources, and indeed has created some that are unique. Here, a personal view is given of some of the achievements to date, and possible future opportunities outlined.
Impact of the Diamond Light Source on research in Earth and environmental sciences: current work and future perspectives
Authors: Burke Ian T. , Mosselmans J. Frederick W. , Shaw Samuel , Peacock Caroline L. , Benning Liane G. , Coker Victoria S.
Published: January 2015

Diamond Light Source Ltd celebrated its 10th anniversary as a company in December 2012 and has now accepted user experiments for over 5 years. This paper describes the current facilities available at Diamond and future developments that enhance its capacities with respect to the Earth and environmental sciences. A review of relevant research conducted at Diamond thus far is provided. This highlights how synchrotron-based studies have brought about important advances in our understanding of the fundamental parameters controlling highly complex mineral–fluid–microbe interface reactions in the natural environment. This new knowledge not only enhances our understanding of global biogeochemical processes, but also provides the opportunity for interventions to be designed for environmental remediation and beneficial use.
The Diamond Light Source and the challenges ahead for structural biology: some informal remarks
Authors: Ramakrishnan V.
Published: January 2015

The remarkable advances in structural biology in the past three decades have led to the determination of increasingly complex structures that lie at the heart of many important biological processes. Many of these advances have been made possible by the use of X-ray crystallography using synchrotron radiation. In this short article, some of the challenges and prospects that lie ahead will be summarized.
Understanding the structural basis for controlling chromosome division
Authors: Barford David
Published: January 2015

The process of chromosome division, termed mitosis, involves a complex sequence of events that is tightly controlled to ensure that the faithful segregation of duplicated chromosomes is coordinated with each cell division cycle. The large macromolecular complex responsible for regulating this process is the anaphase-promoting complex or cyclosome (APC/C). In humans, the APC/C is assembled from 20 subunits derived from 15 different proteins. The APC/C functions to ubiquitinate cell cycle regulatory proteins, thereby targeting them for destruction by the proteasome. This review describes our research aimed at understanding the structure and mechanism of the APC/C. We have determined the crystal structures of individual subunits and subcomplexes that provide atomic models to interpret density maps of the whole complex derived from single particle cryo-electron microscopy. With this information, we are generating pseudo-atomic models of functional states of the APC/C that provide insights into its overall architecture and mechanisms of substrate recognition, catalysis and regulation by inhibitory complexes.
The MYB182 Protein Down-Regulates Proanthocyanidin and Anthocyanin Biosynthesis in Poplar by Repressing Both Structural and Regulatory Flavonoid Genes
Authors: Yoshida Kazuko , Ma Dawei , Constabel C. Peter
Published: January 2015

Trees in the genus Populus (poplar) contain phenolic secondary metabolites including the proanthocyanidins (PAs), which help to adapt these widespread trees to diverse environments. The transcriptional activation of PA biosynthesis in response to herbivory and ultraviolet light stress has been documented in poplar leaves, and a regulator of this process, the R2R3-MYB transcription factor MYB134, has been identified. MYB134-overexpressing transgenic plants show a strong high-PA phenotype. Analysis of these transgenic plants suggested the involvement of additional MYB transcription factors, including repressor-like MYB factors. Here, MYB182, a subgroup 4 MYB factor, was found to act as a negative regulator of the flavonoid pathway. Overexpression of MYB182 in hairy root culture and whole poplar plants led to reduced PA and anthocyanin levels as well as a reduction in the expression of key flavonoid genes. Similarly, a reduced accumulation of transcripts of a MYB PA activator and a basic helix-loop-helix cofactor was observed in MYB182-overexpressing hairy roots. Transient promoter activation assays in poplar cell culture demonstrated that MYB182 can disrupt transcriptional activation by MYB134 and that the basic helix-loop-helix-binding motif of MYB182 was essential for repression. Microarray analysis of transgenic plants demonstrated that down-regulated targets of MYB182 also include shikimate pathway genes. This work shows that MYB182 plays an important role in the fine-tuning of MYB134-mediated flavonoid metabolism.
The WRKY45-2 WRKY13 WRKY42 Transcriptional Regulatory Cascade Is Required for Rice Resistance to Fungal Pathogen
Authors: Cheng Hongtao , Liu Hongbo , Deng Yong , Xiao Jinghua , Li Xianghua , Wang Shiping
Published: January 2015

Blast caused by fungal Magnaporthe oryzae is a devastating disease of rice (Oryza sativa  ) worldwide, and this fungus also infects barley (Hordeum vulgare). At least 11 rice WRKY transcription factors have been reported to regulate rice response to M. oryzae either positively or negatively. However, the relationships of these WRKYs in the rice defense signaling pathway against M. oryzae are unknown. Previous studies have revealed that rice WRKY13 (as a transcriptional repressor) and WRKY45-2 enhance resistance to M. oryzae. Here, we show that rice WRKY42, functioning as a transcriptional repressor, suppresses resistance to M. oryzae. WRKY42-RNA interference (RNAi) and WRKY42-overexpressing (oe) plants showed increased resistance and susceptibility to M. oryzae, accompanied by increased or reduced jasmonic acid (JA) content, respectively, compared with wild-type plants. JA pretreatment enhanced the resistance of WRKY42-oe plants to M. oryzae. WRKY13 directly suppressed WRKY42. WRKY45-2, functioning as a transcriptional activator, directly activated WRKY13. In addition, WRKY13 directly suppressed WRKY45-2 by feedback regulation. The WRKY13-RNAi WRKY45-2-oe and WRKY13-oe WRKY42-oe double transgenic lines showed increased susceptibility to M. oryzae compared with WRKY45-2-oe and WRKY13-oe plants, respectively. These results suggest that the three WRKYs form a sequential transcriptional regulatory cascade. WRKY42 may negatively regulate rice response to M. oryzae by suppressing JA signaling-related genes, and WRKY45-2 transcriptionally activates WRKY13, whose encoding protein in turn transcriptionally suppresses WRKY42 to regulate rice resistance to M. oryzae.
New methods in time-resolved Laue pump–probe crystallography at synchrotron sources
Authors: Coppens Philip , Fournier Bertrand
Published: January 2015

Newly developed methods for time-resolved studies using the polychromatic and in particular the pink-Laue technique, suitable for medium and small-size unit cells typical in chemical crystallography, are reviewed. The order of the sections follows that of a typical study, starting with a description of the pink-Laue technique, followed by the strategy of data collection for analysis with the RATIO method. Novel procedures are described for spot integration, orientation matrix determination for relatively sparse diffraction patterns, scaling of multi-crystal data sets, use of Fourier maps for initial assessment and analysis of results, and least-squares refinement of photo-induced structural and thermal changes. In the calculation of Fourier maps a ground-state structure model, typically based on monochromatic results, is employed as reference, and the laser-ON structure factors for the Fourier summations are obtained by multiplying the reference ground-state structure factors by the square root of the experimental ON/OFF ratios. A schematic of the procedure followed is included in the conclusion section.
Structure of the apo anti-influenza CH65 Fab
Authors: Lee Peter S. , Arnell Ashley J. , Wilson Ian A.
Published: January 2015

Influenza viruses remain a persistent challenge to human health owing to their inherent ability to evade the immune response by antigenic drift. However, the discovery of broadly neutralizing antibodies (bnAbs) against divergent viruses has sparked renewed interest in a universal influenza vaccine and novel therapeutic opportunities. Here, a crystal structure at 1.70 Å resolution is presented of the Fab of the human antibody CH65, which has broad neutralizing activity against a range of seasonal H1 isolates. Previous studies proposed that affinity maturation of this antibody lineage pre-organizes the complementarity-determining region (CDR) loops into an energetically favorable HA-bound conformation. Indeed, from the structural comparisons of free and HA-bound CH65 presented here, the CDR loops, and in particular the heavy-chain CDR3, adopt the same conformations in the free and bound forms. Thus, these findings support the notion that affinity maturation of the CH65 lineage favorably preconfigures the CDR loops for high-affinity binding to influenza hemagglutinin.
Structural analysis of ibuprofen binding to human adipocyte fatty-acid binding protein (FABP4)
Authors: González Javier M. , Fisher S. Zoë
Published: January 2015

Inhibition of human adipocyte fatty-acid binding protein (FABP4) has been proposed as a treatment for type 2 diabetes, fatty liver disease and atherosclerosis. However, FABP4 displays a naturally low selectivity towards hydrophobic ligands, leading to the possibility of side effects arising from cross-inhibition of other FABP isoforms. In a search for structural determinants of ligand-binding selectivity, the binding of FABP4 towards a group of small molecules structurally related to the nonsteroidal anti-inflammatory drug ibuprofen was analyzed through X-ray crystallography. Several specific hydrophobic interactions are shown to enhance the binding affinities of these compounds, whereas an aromatic edge-to-face interaction is proposed to determine the conformation of bound ligands, highlighting the importance of aromatic interactions in hydrophobic environments.
Crystallization and preliminary X-ray crystallographic studies of dipeptidyl peptidase 11 fromPorphyromonas gingivalis
Authors: Sakamoto Yasumitsu , Suzuki Yoshiyuki , Iizuka Ippei , Tateoka Chika , Roppongi Saori , Fujimoto Mayu , Gouda Hiroaki , Nonaka Takamasa , Ogasawara Wataru , Tanaka Nobutada
Published: January 2015

Dipeptidyl peptidase 11 fromPorphyromonas gingivalis(PgDPP11) preferentially cleaves substrate peptides with Asp and Glu at the P1 position [NH2–P2–P1(Asp/Glu)–P1′–P2′…]. For crystallographic studies, PgDPP11 was overproduced inEscherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method. X-ray diffraction data to 1.82 Å resolution were collected from an orthorhombic crystal form belonging to space groupC2221, with unit-cell parametersa= 99.33,b= 103.60,c= 177.33 Å. Structural analysis by the multi-wavelength anomalous diffraction method is in progress.
Crystallization and preliminary X-ray diffraction analysis of a putative carbon–carbon bond hydrolase fromMycobacterium abscessus103
Authors: Zhang Zhang , Jiang Yong-Liang , Wu Yi , He Yong-Xing
Published: January 2015

The PhlG protein fromMycobacterium abscessus103 (mPhlG), which shares 30% sequence identity with phloretin hydrolase fromEubacterium ramulusand 38% sequence identity with 2,4-diacetylphloroglucinol hydrolase fromPseudomonas fluorescensPf-5, is a putative carbon–carbon bond hydrolase. Here, the expression, purification and crystallization of mPhlG are reported. Crystals were obtained using a precipitant consisting of 100 mMcitric acid pH 5.0, 1.0 Mlithium chloride, 8%(w/v) polyethylene glycol 6000. The crystals diffracted to 1.87 Å resolution and belonged to space groupP21, with unit-cell parametersa= 71.0,b= 63.4,c= 74.7 Å, α = 90.0, β = 103.2, γ = 90.0°. Assuming the presence of two mPhlG molecules in the asymmetric unit,VMwas calculated to be 2.5 Å3 Da−1, which corresponds to a solvent content of 50%.
Crystal structure of (μ-N,N′-dibenzyldithiooxamidato-κN,S:N′,S′)bis[(η3-crotyl)palladium(II)]
Authors: Bruno Giuseppe , Lanza Santo , Giannetto Antonino , Sacca Alessandro , Amiri Rudbari Hadi
Published: January 2015

In the centrosymmetric dinuclear title compound, [Pd2(C4H7)2(C16H14N2S2)], the metal atom is η3-coordinated by three C atoms of a crotyl ligand [Pd—C = 2.147 (4), 2.079 (5) and 2.098 (5) Å], the longest distance influenced by the steric interaction with the benzyl substituents of the dibenzyldithiooximidate (DTO) ligand. The Pd—N and Pd—S bonds to this ligand are 2.080 (3) and 2.3148 (9) Å, respectively, completing a square-planar coordination environment for PdII. The benzyl groups are oriented so as to maximize the interaction between a benzylic H atom and an S atom, resulting in a dihedral angle of 77.1 (2)° between the benzene rings and the metal complex plane. In the crystal, no inter-complex hydrogen-bonding interactions are present.
A genetic algorithm for supermarket location problem
Authors: Alnahhal Mohammed , Noche Bernd
Published: January 2015

Purpose

– This purpose of this paper is to investigate the location problem of supermarkets, feeding by material the mixed model assembly lines using tow trains. It determines the number and the locations of these supermarkets to minimize transportation and inventory fixed costs of the system.

Design/methodology/approach

– This is done using integer programming model and real genetic algorithm (RGA) in which custom chromosomes representation, two custom mating and two custom mutation operators were proposed.

Findings

– The performance of RGA is very good since it gives results that are very close or identical to the optimal ones in reasonable CPU time.

Research limitations/implications

– The study is applicable only if a group of supermarkets feed the same assembly line.

Originality/value

– For the first time in supermarket location problem, limitation on availability of some areas for possible supermarkets
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locations and capacity of the supermarkets were taken into consideration.
A model for kitting operations planning
Authors: Caputo Antonio C. , Pelagagge Pacifico M. , Salini Paolo
Published: January 2015

Purpose

– The aim of this paper is to develop a detailed descriptive model for kitting operations, allowing resources sizing and computation of systems’ economic performances.

Design/methodology/approach

– A mathematical model allows to size resources, given product characteristics and production mix, and determines total system costs by assessing relevant cost items including investment costs (vehicles, containers, storage racks), direct operating costs (transport and kitting workforce, vehicles energy consumption and maintenance, quality costs), indirect operating costs (space requirements, work in process (WIP) and safety stock holding costs, administration and control).

Findings

– The choice of parts delivery supply to assembly lines requires a thorough economic comparison of alternatives. However, existing models are often simplistic and neglect many critical factors which affect the systems’ performances. As a consequence, industries are unsure about which system is best for their environment. This model allows assessment of the cost and suitability of kitting in any specific industrial setting. Results of the model application are case-specific and cannot be generalized, but the major impact of labour and error correction cost has been highlighted.

Research limitations/implications

– The model at present focusses on the in-house kitting systems based on travelling kits concept only. Although all quantitative cost drivers are included, some context-related qualitative decision factors are not yet included. The model assumes that the information about product structure and part requirements is known and that a preliminary design of the assembly system (i.e. line balancing) has been carried out.

Practical implications

– Production managers are given a quantitative decision tool to properly assess the implementation of kitting policies at an early decision stage. This allows exploring the trade-offs between the alternatives and properly planning the adoption of kitting systems, as well as comparing kitting with alternative material supply methods.

Originality/value

– With respect to previous simplified literature models, this new approach allows quantification of a number of additional factors which are critical for successful implementation of cost-effective kitting systems, including kitting errors. An exhaustive cost estimation of kitting systems in multiple, mixed-model assembly lines is thus permitted.