53 research outputs found

    Improvisation and Entrepreneurial Journalism: Reimagining Innovation

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    With the rise of innovation and entrepreneurship as avenues for journalists to take in their search for journalistic work, we need to critically interrogate how these terms are understood. Various journalism institutions are pushing a particular understanding of journalism, and of what constitutes meaningful and innovative journalism. In this paper, we review the literature on these themes and draw on experimental research done by one of the authors to argue for a more process-oriented approach to journalistic innovation and entrepreneurship. As a researcher-maker, one of the authors created an innovative journalistic project and tried to develop a business model for this project. She participated in an accelerator process organised by one of the main funds aimed at journalism innovation in the Netherlands. We show that one existing, and prevalent, understanding of innovation in journalism is one that is linear, rational and outcome-oriented. We challenge this understanding and draw on process-oriented theories of innovation to introduce the concepts of effectuation, improvisation and becoming as new lenses to reconsider these phenomena. These concepts provide clearer insight into the passionate and improvisational nature of doing innovative journalistic work

    Virtual reality (VR) as a testing bench for consumer optical solutions: A machine learning approach (GBR) to visual comfort under simulated progressive addition lenses (PALS) distortions

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    For decades, manufacturers have attempted to reduce or eliminate the optical aberrations that appear on the progressive addition lens' surfaces during manufacturing. Besides every effort made, some of these distortions are inevitable given how lenses are fabricated, where in fact, astigmatism appears on the surface and cannot be entirely removed or where non-uniform magnification becomes inherent to the power change across the lens. Some presbyopes may refer to certain discomfort when wearing these lenses for the first time, and a subset of them might never adapt. Developing, prototyping, testing and purveying those lenses into the market come at a cost, which is usually reflected in the retail price. This study aims to test the feasibility of virtual reality for testing customers' satisfaction with these lenses, even before getting them onto production. VR offers a controlled environment where different parameters affecting progressive lens comforts, such as distortions, image displacement or optical blurring, can be analysed separately. In this study, the focus was set on the distortions and image displacement, not taking blur into account. Behavioural changes (head and eye movements) were recorded using the built-in eye tracker. Participants were significantly more displeased in the presence of highly distorted lens simulations. In addition, a gradient boosting regressor was fitted to the data, so predictors of discomfort could be unveiled, and ratings could be predicted without performing additional measurements

    The <em>Bacillus</em> BioBrick Box:Generation and evaluation of essential genetic building blocks for standardized work with Bacillus subtilis

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    Background: Standardized and well-characterized genetic building blocks are a prerequisite for the convenient and reproducible assembly of novel genetic modules and devices. While numerous standardized parts exist for Escherichia coli, such tools are still missing for the Gram-positive model organism Bacillus subtilis. The goal of this study was to develop and thoroughly evaluate such a genetic toolbox. Results: We developed five BioBrick-compatible integrative B. subtilis vectors by deleting unnecessary parts and removing forbidden restriction sites to allow cloning in BioBrick (RFC10) standard. Three empty backbone vectors with compatible resistance markers and integration sites were generated, allowing the stable chromosomal integration and combination of up to three different devices in one strain. In addition, two integrative reporter vectors, based on the lacZ and luxABCDE cassettes, were BioBrick-adjusted, to enable beta-galactosidase and luciferase reporter assays, respectively. Four constitutive and two inducible promoters were thoroughly characterized by quantitative, time-resolved measurements. Together, these promoters cover a range of more than three orders of magnitude in promoter strength, thereby allowing a fine-tuned adjustment of cellular protein amounts. Finally, the Bacillus BioBrick Box also provides five widely used epitope tags (FLAG, His(10), cMyc, HA, StrepII), which can be translationally fused N- or C-terminally to any protein of choice. Conclusion: Our genetic toolbox contains three compatible empty integration vectors, two reporter vectors and a set of six promoters, two of them inducible. Furthermore, five different epitope tags offer convenient protein handling and detection. All parts adhere to the BioBrick standard and hence enable standardized work with B. subtilis. We believe that our well-documented and carefully evaluated Bacillus BioBrick Box represents a very useful genetic tool kit, not only for the iGEM competition but any other BioBrick-based project in B. subtilis

    Access, timing and frequency of very early stroke rehabilitation – insights from the Baden-Wuerttemberg stroke registry

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    Background: While the precise timing and intensity of very early rehabilitation (VER) after stroke onset is still under discussion, its beneficial effect on functional disability is generally accepted. The recently published randomized controlled AVERT trial indicated that patients with severe stroke might be more susceptible to harmful side effects of VER, which we hypothesized is contrary to current clinical practice. We analyzed the Baden-Wuerttemberg stroke registry to gain insight into the application of VER in acute ischemic stroke (IS) and intracerebral hemorrhage (ICH) in clinical practice. Methods: 99,753 IS patients and 8824 patients with ICH hospitalized from January 2008 to December 2012 were analyzed. Data on the access to physical therapy (PT), occupational therapy (OT), and speech therapy (ST), the time from admission to first contact with a therapist and the average number of therapy sessions during the first 7 days of admission are reported. Multiple logistic regression models adjusted for patient and treatment characteristics were carried out to investigate the influence of VER on clinical outcome. Results: PT was applied in 90/87% (IS/ICH), OT in 63/57%, and ST in 70/65% of the study population. Therapy was mostly initiated within 24 h (PT 87/82%) or 48 h after admission (OT 91/89% and ST 93/90%). Percentages of patients under therapy and also the average number of therapy sessions were highest in those with a discharge modified Rankin Scale score of 2 to 5 and lowest in patients with complete recovery or death during hospitalization. The outcome analyses were fundamentally hindered due to biases by individual decision making regarding the application and frequency of VER. Conclusions: While most patients had access to PT we noticed an undersupply of OT and ST. Only little differences were observed between patients with IS and ICH. The staff decisions for treatment seem to reflect attempts to optimize resources. Patients with either excellent or very unfavorable prognosis were less frequently assigned to VER and, if treated, received a lower average number of therapy sessions. On the contrary, severely disabled patients received VER at high frequency, although potentially harmful according to recent indications from the randomized controlled AVERT trial

    Advancing drug discovery through assay development: a survey of tool compounds within the human solute carrier superfamily

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    With over 450 genes, solute carriers (SLCs) constitute the largest transporter superfamily responsible for the uptake and efflux of nutrients, metabolites, and xenobiotics in human cells. SLCs are associated with a wide variety of human diseases, including cancer, diabetes, and metabolic and neurological disorders. They represent an important therapeutic target class that remains only partly exploited as therapeutics that target SLCs are scarce. Additionally, many small molecules reported in the literature to target SLCs are poorly characterized. Both features may be due to the difficulty of developing SLC transport assays that fulfill the quality criteria for high-throughput screening. Here, we report one of the main limitations hampering assay development within the RESOLUTE consortium: the lack of a resource providing high-quality information on SLC tool compounds. To address this, we provide a systematic annotation of tool compounds targeting SLCs. We first provide an overview on RESOLUTE assays. Next, we present a list of SLC-targeting compounds collected from the literature and public databases; we found that most data sources lacked specificity data. Finally, we report on experimental tests of 19 selected compounds against a panel of 13 SLCs from seven different families. Except for a few inhibitors, which were active on unrelated SLCs, the tested inhibitors demonstrated high selectivity for their reported targets. To make this knowledge easily accessible to the scientific community, we created an interactive dashboard displaying the collected data in the RESOLUTE web portal (https://re-solute.eu). We anticipate that our open-access resources on assays and compounds will support the development of future drug discovery campaigns for SLCs

    Diurnal Variation of Intravenous Thrombolysis Rates for Acute Ischemic Stroke and Associated Quality Performance Parameters

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    IntroductionBased on data from the Baden-Wuerttemberg stroke registry, we aimed to explore the diurnal variation of acute ischemic stroke (IS) care delivery.Materials and methods92,530 IS patients were included, of whom 37,471 (40%) presented within an onset-to-door time ≤4.5 h. Daytime was stratified in 3-h time intervals and working vs. non-working hours. Stroke onset and hospital admission time, rate of door-to-neurological examination time ≤30 min, onset-/door-to-imaging time IV thrombolysis (IVT) rates, and onset-/door-to-needle time were determined. Multivariable regression models were used stratified by stroke onset and hospital admission time to assess the relationship between IVT rates, quality performance parameters, and daytime. The time interval 0:00 h to 3:00 h and working hours, respectively, were taken as reference.ResultsThe IVT rate of the whole study population was strongly associated with the sleep–wake cycle. In patients presenting within the 4.5-h time window and potentially eligible for IVT stratification by hospital admission time identified two time intervals with lower IVT rates. First, between 3:01 h and 6:00 h (IVT rate 18%) and likely attributed to in-hospital delays with the lowest diurnal rate of door-to-neurological examination time ≤30 min and the longest door-to-needle time Second, between 6:01 h and 15:00 h (IVT rate 23–25%) compared to the late afternoon and evening hours (IVT rate 27–29%) due to a longer onset-to-imaging time and door-to-imaging time. No evidence for a compromised stroke service during non-working hours was observed.ConclusionThe analysis provides evidence that acute IS care is subject to diurnal variation which may affect stroke outcome. An optimization of IS care aiming at constantly high IVT rates over the course of the day therefore appears desirable

    Dispersion as an Important Step in the Candida albicans Biofilm Developmental Cycle

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    Biofilms are dynamic microbial communities in which transitions between planktonic and sessile modes of growth occur interchangeably in response to different environmental cues. In the last decade, early events associated with C. albicans biofilm formation have received considerable attention. However, very little is known about C. albicans biofilm dispersion or the mechanisms and signals that trigger it. This is important because it is precisely C. albicans cells dispersed from biofilms that are the main culprits associated with candidemia and establishment of disseminated invasive disease, two of the gravest forms of candidiasis. Using a simple flow biofilm model recently developed by our group, we have performed initial investigations into the phenomenon of C. albicans biofilm dispersion, as well as the phenotypic characteristics associated with dispersed cells. Our results indicate that C. albicans biofilm dispersion is dependent on growing conditions, including carbon source and pH of the media used for biofilm development. C. albicans dispersed cells are mostly in the yeast form and display distinct phenotypic properties compared to their planktonic counterparts, including enhanced adherence, filamentation, biofilm formation and, perhaps most importantly, increased pathogenicity in a murine model of hematogenously disseminated candidiasis, thus indicating that dispersed cells are armed with a complete arsenal of “virulence factors” important for seeding and establishing new foci of infection. In addition, utilizing genetically engineered strains of C. albicans (tetO-UME6 and tetO-PES1) we demonstrate that C. albicans biofilm dispersion can be regulated by manipulating levels of expression of these key genes, further supporting the evidence for a strong link between biofilms and morphogenetic conversions at different stages of the C. albicans biofilm developmental cycle. Overall, our results offer novel and important insight into the phenomenon of C. albicans biofilm dispersion, a key part of the biofilm developmental cycle, and provide the basis for its more detailed analysis

    Bedrock geology of DFDP-2B, central Alpine Fault, New Zealand

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    <p>During the second phase of the Alpine Fault, Deep Fault Drilling Project (DFDP) in the Whataroa River, South Westland, New Zealand, bedrock was encountered in the DFDP-2B borehole from 238.5–893.2 m Measured Depth (MD). Continuous sampling and meso- to microscale characterisation of whole rock cuttings established that, in sequence, the borehole sampled amphibolite facies, Torlesse Composite Terrane-derived schists, protomylonites and mylonites, terminating 200–400 m above an Alpine Fault Principal Slip Zone (PSZ) with a maximum dip of 62°. The most diagnostic structural features of increasing PSZ proximity were the occurrence of shear bands and reduction in mean quartz grain sizes. A change in composition to greater mica:quartz + feldspar, most markedly below c. 700 m MD, is inferred to result from either heterogeneous sampling or a change in lithology related to alteration. Major oxide variations suggest the fault-proximal Alpine Fault alteration zone, as previously defined in DFDP-1 core, was not sampled.</p

    Petrophysical, Geochemical, and Hydrological Evidence for Extensive Fracture-Mediated Fluid and Heat Transport in the Alpine Fault's Hanging-Wall Damage Zone

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    International audienceFault rock assemblages reflect interaction between deformation, stress, temperature, fluid, and chemical regimes on distinct spatial and temporal scales at various positions in the crust. Here we interpret measurements made in the hanging‐wall of the Alpine Fault during the second stage of the Deep Fault Drilling Project (DFDP‐2). We present observational evidence for extensive fracturing and high hanging‐wall hydraulic conductivity (∼10−9 to 10−7 m/s, corresponding to permeability of ∼10−16 to 10−14 m2) extending several hundred meters from the fault's principal slip zone. Mud losses, gas chemistry anomalies, and petrophysical data indicate that a subset of fractures intersected by the borehole are capable of transmitting fluid volumes of several cubic meters on time scales of hours. DFDP‐2 observations and other data suggest that this hydrogeologically active portion of the fault zone in the hanging‐wall is several kilometers wide in the uppermost crust. This finding is consistent with numerical models of earthquake rupture and off‐fault damage. We conclude that the mechanically and hydrogeologically active part of the Alpine Fault is a more dynamic and extensive feature than commonly described in models based on exhumed faults. We propose that the hydrogeologically active damage zone of the Alpine Fault and other large active faults in areas of high topographic relief can be subdivided into an inner zone in which damage is controlled principally by earthquake rupture processes and an outer zone in which damage reflects coseismic shaking, strain accumulation and release on interseismic timescales, and inherited fracturing related to exhumation
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