The Fragmented Digital Gaze: The Effects of Multimodal Composition on Narrative Perspective

As society as a whole moves more and more into the multiplicative frames of the digital world, it is important to understand how using these interfaces affects how we think and how we communicate. In this article, the focus is on a creative genre of human communication: narrative. Emerging technologies have historically had various impacts on narrative fiction, from the emergence of mimetic narratives in novel form, to the camera’s influence on techniques such as flashback, and character gaze and perspective. These technologies can be seen to engage in an authorial partnership with the composer, “collaborating to create new media,” new narrative forms and practices. The specific affordances of digital media introduce multimodality, polylinearity, and reader/player interaction to fiction; the practice of composing such multimodal works affects narrative perspective, leading to fragmented and layered narration, metalepsis, and “unnatural narrators.” This article presents research based in the practice of creating a multimodal project, Færwhile (the digital component of this article), examining the progression of narrative perspective from mimetic to unnatural, analyzing the various narrative perspectives. While Richardson argues that the postmodern narrative perspective (utilizing contradictory, permeable, and dis-framed narrators) leads to “postmodern unreliability,” this examination of the Færwhile multimodal narrative will argue that a cohesive voice and its communicated metaphor can be created from the layering of disparate narrative perspectives. The effects described herein have implications for digital engagement and communication on a wider scale, as we attempt to understand how our rapidly evolving technology is also effecting change in our cognition, composition, and understanding of events communicated in digital spaces

Basal forebrain cholinergic system volume is associated with general cognitive ability in the elderly

OBJECTIVE: At the present, it is unclear whether association of basal forebrain cholinergic system (BFCS) volume with cognitive performance exists in healthy as well as in cognitively impaired elderly subjects. Whereas one small study reported an association of BFCS volume with general cognitive ability 'g' in healthy ageing, effects on specific cognitive domains have only been found in subjects with cognitive decline. Here we aim to clarify whether an association of BFCS volume and 'g' is present in a larger sample of elderly subjects without obvious symptoms of dementia and whether similar associations can also be observed in specific cognitive domains. METHODS: 282 pre-surgical patients from the BioCog study (aged 72.7±4.9 years with a range of 65-87 years, 110 women) with a median MMSE score of 29 points (range 24-30) were investigated. BFCS and brain volume as well as brain parenchymal fraction were assessed in T1-weighted MR images using SPM12 and a probabilistic map of the BFCS. Neuropsychological assessment comprised the CANTAB cognitive battery and paper-and-pencil based tests. For data analysis, generalised linear models and quantile regression were applied. RESULTS: Significant associations of BFCS volume with 'g' and several cognitive domains were found, with the strongest association found for 'g'. BFCS volume explained less variance in cognitive performance than brain volume. The association was not confounded by brain parenchymal fraction. Furthermore, the association of BFCS volume and 'g' was similar in high- and low-performers. CONCLUSION: Our results extend previous study findings on BFCS volume associations with cognition in elderly subjects. Despite the observed associations of BFCS volume and cognitive performance, this association seems to reflect a more general association of brain volume and cognition. Accordingly, a specific association of BFCS volume and cognition in non-demented elderly subjects is questionable

A CCR4 antagonist reverses the tumor-promoting microenvironment of renal cancer

CRUK programme grant C587/A16354 and a research grant from Affitech AS.The study was supported by Cancer Research UK (CRUK) programme grant C587/A16354 and a research grant from Affitech AS

The Photodetector Array Camera and Spectrometer (PACS) on the Herschel Space Observatory

The Photodetector Array Camera and Spectrometer (PACS) is one of the three science instruments on ESA's far infrared and submillimetre observatory. It employs two Ge:Ga photoconductor arrays (stressed and unstressed) with 16x25 pixels, each, and two filled silicon bolometer arrays with 16x32 and 32x64 pixels, respectively, to perform integral-field spectroscopy and imaging photometry in the 60-210\mu\ m wavelength regime. In photometry mode, it simultaneously images two bands, 60-85\mu\ m or 85-125\mu\m and 125-210\mu\ m, over a field of view of ~1.75'x3.5', with close to Nyquist beam sampling in each band. In spectroscopy mode, it images a field of 47"x47", resolved into 5x5 pixels, with an instantaneous spectral coverage of ~1500km/s and a spectral resolution of ~175km/s. We summarise the design of the instrument, describe observing modes, calibration, and data analysis methods, and present our current assessment of the in-orbit performance of the instrument based on the Performance Verification tests. PACS is fully operational, and the achieved performance is close to or better than the pre-launch predictions

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

Rapid Discovery of Pyrido[3,4- d ]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach

Monopolar spindle 1 (MPS1) plays a central role in the transition of cells from metaphase to anaphase and is one of the main components of the spindle assembly checkpoint. Chromosomally unstable cancer cells rely heavily on MPS1 to cope with the stress arising from abnormal numbers of chromosomes and centrosomes and are thus more sensitive to MPS1 inhibition than normal cells. We report the discovery and optimization of a series of new pyrido[3,4-d]pyrimidine based inhibitors via a structure-based hybridization approach from our previously reported inhibitor CCT251455 and a modestly potent screening hit. Compounds in this novel series display excellent potency and selectivity for MPS1, which translates into biomarker modulation in an in vivo human tumor xenograft mode

The materiality of the intangible: Literary metaphor in multimodal texts

Based on a larger practice-based research project in digital writing, this article examines how the materiality of digital media contributes to a layered metaphor that delivers meaning, reflects on the cognitive processes (the writer’s and the reader’s) of navigation and generates a dynamic narrative structure through multimodality, unnatural narration and user interaction. Many writers and artists engage with their chosen medium through an instinctive understanding of the materials at hand, gained through experience; the explicit study of a medium’s materiality is not always required for artistic success, however, that may be judged. This article offers insights into the creative process of creating digital, multimodal fiction, based on a practice-based research project designed to explore the effects of digital media on author and text, and argues that digital media have a significant effect on the outcome of the artefact itself. Awareness of these effects, their variations according to hardware and software, and the affordances of these various materials offer the digital writer greater insight and capability to craft his/her texts for the desired metaphorical meaning

Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70.

HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought little success. This study demonstrates that adenosine-derived HSP70 inhibitors potentially bind to the protein with a novel mechanism of action, the stabilization by desolvation of an intramolecular salt-bridge which induces a conformational change in the protein, leading to high affinity ligands. We also demonstrate that through the application of this mechanism, adenosine-derived HSP70 inhibitors can be optimized in a rational manner

Detection of Crosslinks within and between Proteins by LC-MALDI-TOFTOF and the Software FINDX to Reduce the MSMS-Data to Acquire for Validation

Lysine-specific chemical crosslinking in combination with mass spectrometry is emerging as a tool for the structural characterization of protein complexes and protein-protein interactions. After tryptic digestion of crosslinked proteins there are thousands of peptides amenable to MSMS, of which only very few are crosslinked peptides of interest. Here we describe how the advantage offered by off-line LC-MALDI-TOF/TOF mass spectrometry is exploited in a two-step workflow to focus the MSMS-acquisition on crosslinks mainly. In a first step, MS-data are acquired and all the peak list files from the LC-separated fractions are merged by the FINDX software and screened for presence of crosslinks which are recognized as isotope-labeled doublet peaks. Information on the isotope doublet peak mass and intensity can be used as search constraints to reduce the number of false positives that match randomly to the observed peak masses. Based on the MS-data a precursor ion inclusion list is generated and used in a second step, where a restricted number of MSMS-spectra are acquired for crosslink validation. The decoupling of MS and MSMS and the peptide sorting with FINDX based on MS-data has the advantage that MSMS can be restricted to and focused on crosslinks of Type 2, which are of highest biological interest but often lowest in abundance. The LC-MALDI TOF/TOF workflow here described is applicable to protein multisubunit complexes and using 14N/15N mixed isotope strategy for the detection of inter-protein crosslinks within protein oligomers