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This text is a short intellectual biography written in memory of Per Aage Brandt (1944–2021). I present some of the main tenets of his scientific endeavor, artistic practice, and scholarly entrepreneurship.

AIM: To appraise clinical and aesthetic outcomes of connective tissue grafts (CTG) and platelet rich fibrin (PRF) in managing marginal gingival recession METHODS AND MATERIALS: Five patients each with at least two contralateral Miller's Class I and/or Class II recession lesions underwent treatment in a case series with a randomised split-mouth design. Each site was paired with a similar contralateral lesion and randomly assigned to the CTG (control) or PRF (test) treatment. Probing depth, recession depth, recession width, clinical attachment level, keratinised tissue width and gingival thickness were recorded and the data compared. Photographs were taken at baseline and at 24-weeks to evaluate aesthetics using the Pink Esthetic Score (PES). A questionnaire was used to assess patient satisfaction with treatment outcomes. RESULTS AND CONCLUSIONS: Both treatment options resulted in improved clinical measurements but CTGs demonstrated improvements at a greater number of sites than PRF (60% to 30% respectively). The aesthetic scores improved at four sites for both CTGs and PRF with only one site in each group scoring lower, whilst elsewhere scores did not change. Patients were satisfied with the aesthetic outcomes. Both CTGs and PRF membranes can be effective in treating gingival recession, improving clinical and aesthetic outcomes.

George Lakoff and Mark Johnson’s Conceptual Metaphor Theory is by and large a theory of what (abstract) concepts are, how they are structured, and how this structure is acquired — i.e., by mapping of structure from one more concrete or sensory-motor specific domain to another more abstract domain. Conceptual metaphors therefore rest on “cross-domain mappings.” The claims to the effect that our abstract concepts are metaphorically structured and that cross-domain mappings constitute one of the fundamental cognitive meaning-making processes are empirical and can therefore be put to the test. In this paper, I will critically assess Conceptual Metaphor Theory as a theory of concepts in light of recent experimental findings. Many such findings provide evidence for the psychological reality of cross-domain mappings, i.e., that structure activated in one domain actually can perform cognitive tasks carried out in another domain. They do not, however, support the claim that the structure of our (abstract) concepts is still metaphorical, as Lakoff and Johnson claim — that is to say, that our mind actually does perform cross-domain mappings when we process conventional conceptual metaphors such as “Death is Rest” or “Love is a Journey.” Two conclusions can be drawn from this: (1) it is necessary to distinguish between cross-domain mappings (which are psychologically real) and the metaphoric structure of our concepts (which is not, in the sense that such concepts do not any longer activate cross-domain mappings when processed); (2) Conceptual Metaphor Theory is not an adequate theory of concepts. I will therefore sketch another more viable theory of concepts where the structure of our concepts is defined as the fullecologyof their situations of use, which includes the kind of situations (objects, agents, interactions) they apply to and the kind of emotional, cognitive, bodily, and behavioral responses they elicit. On this view, the contents of our concepts are to be considered as vague predicates, with vague extensions, which take on a specific form in their situation of use.

International audience; The REvolutionary Approaches and Devices for Nucleic Acid analysis (READNA) project received 12 million s funding under the European Union Framework Programme 7 from 1st June 2008 to 30th November 2012. The 19 project partners from both academia and industry from in total 7 countries had a project budget of 16 Ms with which they have discovered, created and developed a huge body of insights into nucleic acid analysis. Results have been presented widely in publications and in innumerous public presentations. Results have been moved to spin-offs such as the Olink enrichment kits (now sold by Agilent as Haloplex) and are findingtheir way to the market, such as the Oxford Nanopore MinIon sequencer that was first released to early-access user sites in 2014.

The present work is an attempt to bring meaning to the fore of not only empirical aesthetics but also experimental aesthetics. We have addressed meaning in terms of attention-grabbing perceptual structure, doing so in the strong sense of structure; i.e., structure understood as a pure spatial relation between shapes, independently of what objects these shapes represent. The structures we investigate are the so-called non-generic configurations that obtain between objects seen from a unique vantage point. In the paper, we first introduce the notion of non-genericity, in general, and its use in visual art in particular, where it is claimed to affect the visual brain as an attention grabber. We then present an experiment we have designed to test the effect of such a relation on the visual brain, and we give evidence to the effect that non-generic configurations in pictures do attract attention significantly more than their generic counterparts. Non-genericity can therefore be considered as one among other pictorial techniques artists dispose of to construct perceptual meaning in vision.

This article addresses the phenomenology of aesthetic experience. It first, critically, considers one of the most influential approaches to the psychophysics of aesthetic perception, viz. neuroaesthetics. Hereafter, it outlines constitutive tenets of aesthetic perception in terms of a particular intentional relation to the object. The argument comes in three steps. First, I show the inadequacies of the neuroaesthetics of beauty in general and Semir Zeki’s and V.J. Ramachandran’s versions of it in particular. The neuroaesthetics of beauty falls short, because it develops hypotheses of aesthetic experience which have no consequences for the understanding of what art is, that is, how artists produce visual meaning effects in their works. This is so because they make the rewarding feeling of beauty the cornerstone of aesthetic experience. Next, I show why and how aesthetic experience should be defined relative to its object and the tools for meaning-making specific to that object, and not relative to the feeling (of beauty) it may elicit. Finally, I sketch the import this fact may have on a research program in empirical aesthetics.

The paper considers the phenomenology of aesthetic experience as “twofold” in a sense akin to Wollheim’s (Painting as an art. Princeton University Press, Princeton, 1987). However, as regards the perception of artworks proper, the notion of twofoldness needs further specification. In the wake of Wollheim, the philosophy of pictorial representation has addressed the second, ‘configurational’ aspect of twofoldness in rather vague terms without addressing the aesthetic or pictorial function of this correlate of aesthetic perception. I shall talk about such co-awareness as “design-seeing” and assign two decisive properties to pictorial design. First, I will point to a depicting property of design that is a distinctive property of pictures. Design in pictures is such that it can depict two (or, in rare cases, even more) fully consistent objects without the picture becoming ambiguous. Next, I’ll show that the design structure of a painting is not simply a structure in virtue of which something is represented to the eye, but also in virtue of which meaning is conveyed to the eye. If I am right in considering the design level of pictures as a genuine platform for meaning making, then seeing-in doubled with design seeing occurs every time lines and shapes do not only depict, but also mean something

Circulating microRNAs in human serum have increasingly been recognized as stable markers for cancer detection. However, there is still a lack of miRNome wide studies over a long period of time with respect to pathogenic processes. We obtained serum samples from the janus serum bank collected prior and after diagnosis of lung cancer. We analyzed the abundance of 904 miRNAs in serum from eight cancer patients at three time points and from six healthy control individuals. Based on the identified miRNA signatures, hierarchical clustering and a self-organizing map identified three major clusters including one cluster containing most of the of the pre-diagnostic samples, a second cluster with mainly post-diagnostic samples, and a third cluster with mainly control samples. Correlation analyses showed that although the profiles were generally stable over several years, most obvious changes of the miRNA pattern seem to occur at a time close to diagnosis. Our findings support the idea that a developing lung cancer might be detectable years prior to diagnosis through a specific miRNA signature and that this signature changes during tumor development.

Background— Today, mutations in more than 30 different genes have been found to cause inherited cardiomyopathies, some associated with very poor prognosis. However, because of the genetic heterogeneity and limitations in throughput and scalability of current diagnostic tools up until now, it is hardly possible to genetically characterize patients with cardiomyopathy in a fast, comprehensive, and cost-efficient manner. Methods and Results— We established an array-based subgenomic enrichment followed by next-generation sequencing to detect mutations in patients with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). With this approach, we show that the genomic region of interest can be enriched by a mean factor of 2169 compared with the coverage of the whole genome, resulting in high sequence coverage of selected disease genes and allowing us to define the genetic pathogenesis of cardiomyopathies in a single sequencing run. In 6 patients, we detected disease-causing mutations, 2 microdeletions, and 4 point mutations. Furthermore, we identified several novel nonsynonymous variants, which are predicted to be harmful, and hence, might be potential disease mutations or modifiers for DCM or HCM. Conclusions— The approach presented here allows for the first time a comprehensive genetic screening in patients with hereditary DCM or HCM in a fast and cost-efficient manner.

Instead of considering key concepts of narratology such as focalization (perspective) or mode of narration (teller vs. reflector, as Franz K. Stanzel has it) simply as criteria for a typology of texts, this paper intends to activate them as ‘symbolic forming tools’ or ‘means of meaning making’ in literary art. The fundamental claim is that an author can activate or apply them in various ways—experimenting with them—in order to obtain given meaning effect within one and the same text. Through analysis of examples it is shown how authors' variations on the focalization, the narrative mode, and the granularity axes produce semiotic effects amenable to systematic characterization. A recurrent concern in the paper is the representation of consciousness in literary art.

In this paper I introduce some of the principles which rule meaning making in visual artworks — both in regard to construction and interpretation of meaning. The approach is naturalistic in that aesthetic meaning construction is claimed to rest on features and structures which are intrinsically significant for the visuo-cognitive system in plain, everyday perception: the artist exploits such features, and so doing he transforms the automatisms of perception into a rhetoric of aesthetic intuition. Section 1 of the paper consists of a phenomenological characterization of the aesthetic object as such (in its difference from everyday objects). In the core of the present work, section 2, I give concrete examples (with a general import) of the meaning making tools used in visual art and their roots in everyday perception. The central concern here is to show how purely spatial relations can become significant, or, in other words, how conceptual meaning can be anchored in perception, or, finally, how artists can encode meaning in shape. The final section discusses the general principles ruling the semiotics of the visual artwork and addresses a couple of methodological issues.

This paper provides a precis of Ernst Cassirer’s concept of art as a symbolic form. It does so, though, in a specific respect. It points to the fact that Cassirer’s concept of “symbolic form” is two-sided. On the one hand, the concept captures general cultural phenomena that are not only meaningful but also manifest the way man makes sense of the world; thus myth, religion, and art are considered general symbolic forms. On the other hand, it captures the formal structures and semiotic tools thanks to which meaning is constructed within each general symbolic form (Cassirer called these structures “modes of objectivation”); thus, in art, perspective or the golden section are well-known examples of symbolic forms, now in a narrow sense, i.e. they are means to configure parts into an organized, meaningful whole. The paper will comment on art along both these two dimensions, but its main goal is to provide with concrete examples of aesthetic symbolic forms in the narrow sense in order to show how conceptual meaning can be inscribed in the space of aesthetic intuition.

This paper develops a characterization of nominal compounds. The analysis is carried oui on frame-schematic and construction-grammatical grounds. It rests on assumptions about cognitive processing long since known within cognitive linguistics, but it criticizes certain linguistic applications of Fauconnier & Turner's theory of conceptual integration. A crucial difference between the processing of literal and metaphorical compounds is established. Thus, the approach has a double scope: it aims at characterizing both the semantics of compounds and the way the semantics is cognitively accessed. Our article fits into the theme of this volume by proposing a theory that we believe is much more precise than previous accounts about the semantic input, or ‘instructions’, that the linguistic items bring to the process of meaning construction.

This article has a double scope. First, we consider the dynamics inherent in the emergence of genres. Our view is that genres emerge relative to two sets of

This book investigates the nature of aesthetic experience and aesthetic objects. Written by leading philosophers, psychologists, literary scholars and semioticians, the book addresses two intertwined issues. The first is related to the phenomenology of aesthetic experience: The understanding of how human beings respond to artworks, how we process linguistic or visual information, and what properties in artworks trigger aesthetic experiences. The examination of the properties of aesthetic experience reveals essential aspects of our perceptual, cognitive, and semiotic capacities. The second issue studied in this volume is related to the ontology of the work of art: Written or visual artworks are a specific type of objects, containing particular kinds of representation which elicit a particular kind of experience. The research question explored is: What properties in artful objects trigger this type of experience, and what characterizes representation in written and visual artworks? The volume sets the scene for state-of-the-art inquiries in the intersection between the psychology and ontology of art. The investigations of the relation between the properties of artworks and the characteristics of aesthetic experience increase our insight into what art is. In addition, they shed light on essential properties of human meaning-making in general.

The present investigation challenges the traditional distinction between cohesion and coherence; i.e., the distinction between the syntactical rules governing the composition of lexical units within the scope of the clause and the semantic-pragmatic rules guiding the composition of text units beyond the scope of the clause. To this end it exposes two major principles of semantic combination that are active through all levels of linguistic composition: viz. frame-schematic structure and narrative structure. These principles are considered as being components of a semantic combinatorial system to be determined in terms of dependency relations.

Det narrative skema som grundlæggende kognitivt skema Cognition and narrativityThis paper aims at establishing the origin of the narrative schema in the perception of intentional movements. The distinction between mechanical and intentional movements is vital for human beings, and the narrative schema, which is underpinned by this distinction, is therefore claimed to be a basic cognitive principle of intelligibility. This is the reason why the narrative schema is by no means confined to the domain of the literary work of art or telling in general. It is rather a major principle for the combination of partial significations in many other domains. The paper explores the role traditionally assigned to the narrative schema within continental semiotics, and through an interpretation of Heider & Simmel’s study on apparent behavior it establishes the cognitive import of the narrative schema and its origin in visual perception; finally it gives examples of the meaning-organizing import of the narrative schema.

One of the central issues in linguistics is whether or not language should be considered a self-contained, autonomous formal system, essentially reducible to the syntactic algorithms of meaning construction (as Chomskyan grammar would have it), or a holistic-functional system serving the means of expressing pre-organized intentional contents and thus accessible with respect to features and structures pertaining to other cognitive subsystems or to human experience as such (as Cognitive Linguistics would have it). The latter claim depends critically on the existence of principles governing the composition of semantic contents. Husserl's fourth Logical Investigation is well known as a genuine precursor for Chomskyan grammar. However, I will establish the heterogeneous character of the Investigation and show that the whole first part of it is devoted to the exposition of a semantic combinatorial system cognate to the one elaborated within Cognitive Linguistics. I will thus show how theoretical results in linguistics may serve to corroborate and shed light on those parts of Husserl's Fourth Investigation that have traditionally been dismissed as vague or simply ignored.

This article assesses two objections directed at Conceptual Metaphor Theory: (1) it is circular in that it only provides linguistic evidence for the psychological reality of cross-domain mappings, intended to explain the empirical reality of metaphorical expressions in language; (2) it does not support the conclusion that the massive existence of metaphorical expressions in language reflects the metaphorical structuring of abstract concepts. It is my aim to disentangle these objections. Evidence abounds that makes the first objection obsolete, proving the psychological reality of cross-domain mappings. However, this does not imply that abstract concepts are metaphorically structured: experiments that prove objection (1) wrong cannot be invoked to reject objection (2). Some even tend to justify it.

How is linguistic communication possible? How do we come to share the same meanings of words and utterances? One classical position holds that human beings share a transcendental "platonic" ideality independent of indi- vidual cognition and language use (Frege 1948). Another stresses immanent lin- guistic relations (Saussure 1959), and yet another basic embodied structures as the ground for invariant aspects of meaning (Lakoff and Johnson 1999). Here we propose an alternative account in which the possibility for sharing meaning is motivated by four sources of structural stability: 1) the physical constraints and affordances of our surrounding material environment, 2) biological constraints of our human bodies, 3) social normative constraints of culture and society, and 4) the local history of social interactions. These structures and constraints interact in dynamical ways in actual language usage situations: local dialogical and social dynamics motivate and stabilize the profiling of a conceptual space already highly structured by our shared biology, culture, and environment. We will sub- stantiate this perspective with reference to recent studies in experimental prag- matics and semiotics in which participants interact linguistically to solve coop- erative tasks. Three main cases will be considered: The dynamic grounding of linguistic categories, the construction of conceptual models to relate entities in a scene, and the construction of shared conceptual scales for assessing and ap- praising subjective experiences.

Roman Ingarden (1973a, 1973b) developed an ontology of the literary artwork with implications for a theory of reader experience. An upshot of the fact that narratives represent only incompletely determined states of affairs, endowed with “spots of indeterminacy,” is that readers fill out the blanks left by the author. Filling-out is therefore considered a quasi perceptual act leading to the constitution of a full object in the reader’s experience. In this paper, I challenge the degree to which readers’ concretization of texts depends on such completing acts. I point to the fact that perception itself is schematic, and that the analogy to perception would rather imply that concretization does not imply full filling-out. On the contrary, there seems to be a correspondence between the standard level of descriptive granularity in literature and the schematic coarse-grainedness of perception. To corroborate this claim, I show how deviations from that descriptive baseline produce a variety of meaning effects.

In a multicenter study, we determined the expression profiles of 863 microRNAs by array analysis of 454 blood samples from human individuals with different cancers or noncancer diseases, and validated this 'miRNome' by quantitative real-time PCR. We detected consistently deregulated profiles for all tested diseases; pathway analysis confirmed disease association of the respective microRNAs. We observed significant correlations (P = 0.004) between the genomic location of disease-associated genetic variants and deregulated microRNAs.

The construction of synthetic biological systems involving millions of nucleotides is limited by the lack of high-quality synthetic DNA. Consequently, the field requires advances in the accuracy and scale of chemical DNA synthesis and in the processing of longer DNA assembled from short fragments. Here we describe a highly parallel and miniaturized method, called megacloning, for obtaining high-quality DNA by using next-generation sequencing (NGS) technology as a preparative tool. We demonstrate our method by processing both chemically synthesized and microarray-derived DNA oligonucleotides with a robotic system for imaging and picking beads directly off of a high-throughput pyrosequencing platform. The method can reduce error rates by a factor of 500 compared to the starting oligonucleotide pool generated by microarray. We use DNA obtained by megacloning to assemble synthetic genes. In principle, millions of DNA fragments can be sequenced, characterized and sorted in a single megacloner run, enabling constructive biology up to the megabase scale.

Background While more than 700 microRNAs (miRNAs) are known in human, a comparably low number has been identified in swine. Because of the close phylogenetic distance to humans, pigs serve as a suitable model for studying e.g. intestinal development or disease. Recent studies indicate that miRNAs are key regulators of intestinal development and their aberrant expression leads to intestinal malignancy. Results Here, we present the identification of hundreds of apparently novel miRNAs in the porcine intestine. MiRNAs were first identified by means of deep sequencing followed by miRNA precursor prediction using the miRDeep algorithm as well as searching for conserved miRNAs. Second, the porcine miRNAome along the entire intestine (duodenum, proximal and distal jejunum, ileum, ascending and transverse colon) was unraveled using customized miRNA microarrays based on the identified sequences as well as known porcine and human ones. In total, the expression of 332 intestinal miRNAs was discovered, of which 201 represented assumed novel porcine miRNAs. The identified hairpin forming precursors were in part organized in genomic clusters, and most of the precursors were located on chromosomes 3 and 1, respectively. Hierarchical clustering of the expression data revealed subsets of miRNAs that are specific to distinct parts of the intestine pointing to their impact on cellular signaling networks. Conclusions In this study, we have applied a straight forward approach to decipher the porcine intestinal miRNAome for the first time in mammals using a piglet model. The high number of identified novel miRNAs in the porcine intestine points out their crucial role in intestinal function as shown by pathway analysis. On the other hand, the reported miRNAs may share orthologs in other mammals such as human still to be discovered.

Sequence capture methods for targeted next generation sequencing promise to massively reduce cost of genomics projects compared to untargeted sequencing. However, evaluated capture methods specifically dedicated to biologically relevant genomic regions are rare. Whole exome capture has been shown to be a powerful tool to discover the genetic origin of disease and provides a reduction in target size and thus calculative sequencing capacity of >90-fold compared to untargeted whole genome sequencing. For further cost reduction, a valuable complementing approach is the analysis of smaller, relevant gene subsets but involving large cohorts of samples. However, effective adjustment of target sizes and sample numbers is hampered by the limited scalability of enrichment systems. We report a highly scalable and automated method to capture a 480 Kb exome subset of 115 cancer-related genes using microfluidic DNA arrays. The arrays are adaptable from 125 Kb to 1Mb target size and/or one to eight samples without barcoding strategies, representing a further 26 – 270-fold reduction of calculative sequencing capacity compared to whole exome sequencing. Illumina GAII analysis of a HapMap genome enriched for this exome subset revealed a completeness of >96%. Uniformity was such that >68% of exons had at least half the median depth of coverage. An analysis of reference SNPs revealed a sensitivity of up to 93% and a specificity of 98.2% or higher.

From a purely quantitative point of view, Edmund Husserl has devoted a rather small amount of time and space to the study of language proper. Essentially, his contributions within this domain amount to the description of language use in the First Logical Investigation (Husserl 1901), and the determination of the essential properties of language as such (independent of any specific use) in the Fourth Logical Investigation. Otherwise, language is only sparsely dealt with in Husserl’s writings: the unpublished note “On the Logic of Signs (Semiotics)” (Husserl 1890) anticipates the distinction between “expression” and “index” which constitutes the starting point of the First Logical Investigation; i.e. the difference between a linguistic or any other sign bestowed with intentional meaning and any type of sign which is immediately or physically linked to its meaning: smoke → fire; scar → wound; weathercock → wind, etc.); Formal and Transcendental Logic (Husserl 1929) contains an appendix related to the theory of syntax outlined in the Fourth Logical Investigation; and, finally, a number of passages from Experience and Judgment (Husserl 1939) reexamine the relation between perceptually formed or antepredicatively structured meaning and its linguistic, predicative articulation (as we shall see this issue is also in the heart of the discussions unfolded in the Fourth Logical Investigation).

A strategy allowing for amplification, detection and genotyping of different genomic DNA targets in a single reaction container is described. The method makes use of primer-directed solution-phase amplification with integrated labeling in a closed, microfluidic oligonucleotide array. Selective array probes allow for subsequent detection and genotyping of generated amplicons by hybridization. The array contains up to 15,624 programmable features that can be designed, de novo synthesized and tested within 24 hours using an automated benchtop microarray synthesizer. This enables rapid prototyping and adaptation of the system to newly emerging targets such as pathogenic bacterial or viral subtypes. The system was evaluated by amplifying and detecting different loci of viral (HPV), bacterial (Bacillus sp.) and eukaryotic (human) genomes. Multiplex PCR and semi-quantitative detection with excellent detection limits of

We report a flexible method for selective capture of sequence fragments from complex, eukaryotic genome libraries for next-generation sequencing based on hybridization to DNA microarrays. Using microfluidic array architecture and integrated hardware, the process is amenable to complete automation and does not introduce amplification steps into the standard library preparation workflow, thereby avoiding bias of sequence distribution and fragment lengths. We captured a discontiguous human genomic target region of 185 kb using a tiling design with 50mer probes. Analysis by high-throughput sequencing using an Illumina/ Solexa 1G Genome Analyzer revealed 2150-fold enrichment with mean per base coverage between 4.6 and 107.5-fold for the individual target regions. This method represents a flexible and cost-effective approach for large-scale resequencing of complex genomes.

Small noncoding RNAs (sncRNAs) have moved from oddity to recognized important players in gene regulation. Next generation sequencing approaches discover more and more such molecules from a variety of different groups, but flexible tools translating this sequence information into affordable high-throughput assays are missing. Here we describe a microfluidic primer extension assay (MPEA) for the detection of sncRNAs on highly flexible microfluidic microarrays which combines several beneficial parameters: it can effortless incorporate any new sequence information; it is sensitive enough to work with as little as 20ng of total RNA and has a high level of specificity owing to a combination of a conventional hybridization assay and an enzymatic elongation step. Importantly, no labeling step is needed before hybridization and - because of its high sensitivity - no amplification is required. Both aspects ensure that no bias is introduced by such processes. Although the assay is exemplified with miRNAs, the flexibility of the technology platform allows the analysis of any type of sncRNA, such as piRNAs.

Our paper rejects Anders Sogaard's claim in Semiotica 169 (1/4) to the effect that our article ' Waterproof fire stations? Conceptual schemata and cognitive operations involved in compound constructions' in Semiotica 161 (1/4) goes astray in that it is 'monoconstructional' when it ought to be 'multiconstructional.' We demonstrate point by point that Sogaard's objections are wrong, not only as regards the argument, but also, as regards plain empirical assertions. In our paper we 1. redevelop our notion of 'construction'; 2. refute Sogaard's objections, both formally and empirically.

This text has two parts. In the first section, we intend to define the narrative schema - the canonical plot structure - as a symbolic form in Ernst Cassirer's sense of the term. This basically implies that the narrative schema is not an invariant higher order combinatorial form, but may itself be subject to variations in view of yielding specific meaning effects. This is because the production and reception of a narrative is a dynamic process where physical forces, modal forces and intentions set up a space of possibilities for the narrative trajectory. We therefore propose a determination of the narrative schema in terms of force dynamics.' In the next section we proceed to an analysis of Ernst Hemingway's 'A Very Short Story' in order to illustrate this point. We lay down the main elements of its remarkable, if not simply outstanding both narrative and semantic-configurational structure: its plot structure is indeed driven by an inverted narrative schema and each significant event in the story but one (as well as each physical paragraph but one) has its rigorously symmetrical counterpart. Moreover, this inverted schema can be explained in terms of the modal forces at stake in the narrative.

Hybridization of rRNAs to microarrays is a promising approach for prokaryotic and eukaryotic species identification. Typically, the amount of bound target is measured by fluorescent intensity and it is assumed that the signal intensity is directly related to the target concentration. Using thirteen different eukaryotic LSU rRNA target sequences and 7693 short perfect match oligonucleotide probes, we have assessed current approaches for predicting signal intensities by comparing Gibbs free energy (DeltaG degrees) calculations to experimental results. Our evaluation revealed a poor statistical relationship between predicted and actual intensities. Although signal intensities for a given target varied up to 70-fold, none of the predictors were able to fully explain this variation. Also, no combination of different free energy terms, as assessed by principal component and neural network analyses, provided a reliable predictor of hybridization efficiency. We also examined the effects of single-base pair mismatch (MM) (all possible types and positions) on signal intensities of duplexes. We found that the MM effects differ from those that were predicted from solution-based hybridizations. These results recommend against the application of probe design software tools that use thermodynamic parameters to assess probe quality for species identification. Our results imply that the thermodynamic properties of oligonucleotide hybridization are by far not yet understood.

The paper develops a characterization of nominal compounds. The analysis is carried out on frame-schematic and construction-grammatical grounds. It rests on assumptions about cognitive processing long since known within cognitive linguistics, but it criticizes certain linguistic applications of Fau- connier and Turner's theory of conceptual integration, which historically is a reelaboration of Lakoand Johnson's theory of metaphor. The first section sums up two classical approaches in the analysis of nom- inal compounds; it comments on their inadequacies, and how these have been assessed by Fauconnier and Turner; next, it sketches out the way these two authors and other scholars in blending theory have traditionally ana- lyzed nominal compounds in terms of conceptual integration, and finally one of the major drawbacks of this approach is identified: namely, its lim- ited descriptive import. In the following section, the authors unfold their own semantic analysis. A non-trivial and non-standard compositional theory is proposed, likely to capture the general way in which semantic parts of a compound configure into a semantic whole. Hereafter the authors proceed to a summary survey of how this scaolding is actually instantiated or processed cognitively. A crucial dierence between processing of literal and metaphorical com- pounds is established. Thus, the approach has a double scope: it aims at characterizing both the semantics of compounds and the way the semantics is cognitively accessed.

The successful completion of the Human Genome Project and other sequencing projects opened the door for another quantum jump in science advancement. The most important public sequence databases are doubling in size every 18 months. By revealing the genetic program of many organisms, these efforts endow biologists with the ability to study the basic information of life in toto as an initial step toward a comprehensive understanding of the complexity of entire organisms. We review the area of synthetic biology, defined as the making and use of biosystems founded on the chemical synthesis of the coding DNA (and potentially RNA). The recent developments discussed here introduce a rich source of oligonucleotides to the field: in situ synthesised microarrays, which in fact represent nothing else but matrix nucleic acid synthesisers. With this new way of producing the oligonucleotides used in the making of synthetic genes in a very cost-effective manner, the field of synthetic biology can be expected to change dramatically in the next decade. Synthetic genes will then be the tools of choice to obtain any sequence at any time in any laboratory.

Here we describe a novel microarray platform that integrates all functions needed to perform any array-based experiment in a compact instrument on the researcher's laboratory benchtop. Oligonucle otide probes are synthesized in situ via a light- activated process within the channels of a three-dimensional microfluidic reaction carrier. Arrays can be designed and produced within hours according to the user's requirements. They are processed in a fully automatic workflow. We have characterized this new platform with regard to dynamic range, discrimination power, reproducibility and accuracy of biological results. The instrument detects sample RNAs present at a frequency of 1:100 000. Detection is quantitative over more than two orders of magnitude. Experiments on four identical arrays with 6398 features each revealed a mean coefficient of variation (CV) value of 0.09 for the 6398 unprocessed raw intensities indicating high reproducibility. In a more elaborate experiment targeting 1125 yeast genes from an unbiased selection, a mean CV of 0.11 on the fold change level was found. Analyzing the transcriptional response of yeast to osmotic shock, we found that biological data acquired on our platform are in good agreement with data from Affymetrix GeneChips, quantitative real-time PCR and--albeit somewhat less clearly--to data from spotted cDNA arrays obtained from the literature.

Background Compared to classical genotyping, targeted next-generation sequencing (t NGS) can be custom-designed to interrogate entire genomic regions of interest, in order to detect novel as well as known variants. To bring down the per-sample cost, one approach is to pool barcoded NGS libraries before sample enrichment. Still, we lack a complete understanding of how this multiplexed t NGS approach and the varying performance of the ever-evolving analytical tools can affect the quality of variant discovery. Therefore, we evaluated the impact of different software tools and analytical approaches on the discovery of single nucleotide polymorphisms (SNPs) in multiplexed t NGS data. To generate our own test model, we combined a sequence capture method with NGS in three experimental stages of increasing complexity (E. coli genes, multiplexed E. coli, and multiplexed HapMap BRCA1/2 regions). Results We successfully enriched barcoded NGS libraries instead of genomic DNA, achieving reproducible coverage profiles (Pearson correlation coefficients of up to 0.99) across multiplexed samples, with Conclusions We recommend applying our general ‘two-step’ mapping approach for more efficient SNP discovery in t NGS. Our study has also shown the benefit of computing inter-sample SNP-concordances and inspecting read alignments in order to attain more confident results.

Background: Although the site of nosocomial sepsis in the critically ill ventilated patient is usually identifiable, it may remain occult, despite numerous investigations. The rapid results and precise anatomical location of the septic source using positron emission tomography (PET) scanning, in combination with computed tomography (CT), has promoted this modality as the diagnostic tool of choice for pyrexias of unknown origin.Methods: The objective of this study was to report our experience using PET/CT scanning for the localisation of a septic focus in critically injured patients in whom no source could be identified using conventional investigations.Results: Two patients with gunshot wounds and two who had sustained multiple fractures following motor vehicle collisions developed pyrexias of unknown origin during their stay in the trauma intensive care unit. Routine screening for a septic focus was unrewarding, and 18F-fluorodeoxyglucose PET/CT scanning was used to identify the possible source. PET/CT scanning identified the septic focus in all patients. Abscesses were drained successfully in those with penetrating trauma and in one with blunt polytrauma. Pulmonary tuberculosis, not apparent on initial radiology, was identified using PET/CT in one patient with blunt thoracic trauma.Conclusion: PET/CT scanning appears to both confirm and localise the source of sepsis in a variety of pathologies in critically ill patients who develop pyrexias for which no source can be identified by conventional screening techniques.

International audience; Narrative Theories and Poetics: 5 Questions is a collection of short interviews based on five provoking questions presented to some of the most influential and prominent scholars in these fields. They present us with their views on narrative theories and poetics, its aim, scope, use, the future direction of the fields and how their work fits in these respects.