Chapter Shifting Times, Converging Futures: Technologies of Writing Beyond Poggio Bracciolini

Bracciolini’s contribution to visual materiality, graphical innovation, and the book trade is the driving force in the development of a new philological turn. This essay explores the textual consciousness that marked the passage to scrupulous criteria of editing and writing, which ultimately indicates and emphasizes the historical dimension of hermeneutical tradition. With a powerful impact on readership and authorship, Bracciolini stands behind this groundbreaking entanglement, as we rethink textual transmission and modern scholarship in this digital age

Chapter Introduction

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Repurposing Digital Methods for Human-Centered Design:Distilling Data-Driven Personas from Twitter Discussions: The case of Urban Nature in Paris

From logs and information left in online spaces to data points self-generated by connected devices, digital traces have become more diffused over the past years, prompting an expansion of Human-Centered Design methods. Along with some bigdata approaches, Digital Methods of research – treating the actual content of digital users’ manifestation on-line (i.e. tweets, Instagram pictures, comments) – offer the opportunity to better understand users through their online activities. This paper investigates how Digital Methods can be repurposed as a full-fledged approach for Human-Centered Design. Grafting on the NATURPRADI project – a research aimed at describing the debate raised by the re-vegetation of the city of Paris by analysing Twitter posts – in the paper we will explain how we have identified and described a set of personas characterized by different approaches towards the evolution of the urban nature issue. The final objective of the paper is to provide a first methodological tool created at the intersection of Digital Methods and Human-Centered Design discussing its opportunities and criticalities: Data-driven Personas

Digital Methods for Service Design:Experimenting with data-driven frameworks

From logs and information left in online spaces to data points self-generated by connected devices, digital traces have become more and more diffused over the past years. Along with some big-data approaches, Digital Methods of research - treating the actual content of users’ manifestation online (i.e. tweets, Instagram pictures, comments) - offer the opportunity to better understand people and behaviors through their online activities. This paper investigates how Digital Methods can be repurposed as a full-fledged approach for the Service Design practice, by offering a method to outline service design frameworks from a corpus of web data. This quantitative methods, in combination with the traditional qualitative approaches, leverage the continuous exchange of information that is happening in the digital space and suggest the possibility to automate parts of the data collection and analysis processes in support of service design activities. Grafting on several case studies - we will explain how Digital Methods could be used to identify and describe a set of personas by extracting and interpreting data from their online activities, and we will inquire into the application of the same methodological approach to map other frameworks - such as experience journeys or system maps - that are critical to Service Design

Caspase-mediated loss of mitochondrial function and generation of reactive oxygen species during apoptosis

During apoptosis, the permeabilization of the mitochondrial outer membrane allows the release of cytochrome c, which induces caspase activation to orchestrate the death of the cell. Mitochondria rapidly lose their transmembrane potential (ΔΨm) and generate reactive oxygen species (ROS), both of which are likely to contribute to the dismantling of the cell. Here we show that both the rapid loss of ΔΨm and the generation of ROS are due to the effects of activated caspases on mitochondrial electron transport complexes I and II. Caspase-3 disrupts oxygen consumption induced by complex I and II substrates but not that induced by electron transfer to complex IV. Similarly, ΔΨm generated in the presence of complex I or II substrates is disrupted by caspase-3, and ROS are produced. Complex III activity measured by cytochrome c reduction remains intact after caspase-3 treatment. In apoptotic cells, electron transport and oxygen consumption that depends on complex I or II was disrupted in a caspase-dependent manner. Our results indicate that after cytochrome c release the activation of caspases feeds back on the permeabilized mitochondria to damage mitochondrial function (loss of ΔΨm) and generate ROS through effects of caspases on complex I and II in the electron transport chain

Fiberoptic monitoring of central venous oxygen saturation (PediaSat) in small children undergoing cardiac surgery: continuous is not continuous

Background: Monitoring of superior vena cava saturation (ScvO2) has become routine in the management of pediatric patients undergoing cardiac surgery. The objective of our study was to evaluate the correlation between continuous ScvO2 by the application of a fiber-optic oximetry catheter (PediaSat) and intermittent ScvO2 by using standard blood gas measurements. These results were compared to those obtained by cerebral near infrared spectroscopy (cNIRS). Setting: Tertiary pediatric cardiac intensive care unit (PCICU). Methods and main results: A retrospective study was conducted in consecutive patients who were monitored with a 4.5 or 5.5 F PediaSat catheter into the right internal jugular vein. An in vivo calibration was performed once the patient was transferred to the PCICU and re-calibration took place every 24 hours thereafter. Each patient had a NIRS placed on the forehead. Saturations were collected every 4 hours until extubation. Ten patients with a median age of 2.2 (0.13-8.5) years and a weight of 12.4 (3.9-24) kg were enrolled. Median sampling time was 32 (19-44) hours: 64 pairs of PediaSat and ScVO2 saturations showed a poor correlation (r=0.62, 95% CI 44-75; p<0.0001) and Bland Altman analysis for repeated measures showed an average difference of 0.34 with a standard deviation of 7,9 and 95% limits of agreement from -15 to 16. Thirty-six pairs of cNIRS and ScVO2 saturations showed a fair correlation (r=0.79, 95% CI 0.60-0.89; p<0.0001) an average difference of -1.4 with a standard deviation of 6 and 95% limits of agreement from -13 to 10. Analysis of median percentage differences between PediaSat and ScvO2 saturation over time revealed that, although not statistically significant, the change in percentage saturation differences was clinically relevant after the 8th hour from calibration (from -100 to +100%). Conclusion: PediaSat catheters showed unreliable performance in our cohort. It should be further investigated whether repeating calibrations every 8 hours may improve the accuracy of this system. CNIRS may provide similar results with a lower invasiveness

PO-473 Quantification of ERCC1-XPF complexes in ovarian cancer xenografts with different sensitivity to cisplatin

Introduction Epithelial ovarian cancer is the most lethal gynaecological cancer due to the development of resistance to a platinum based therapy. As DNA repair capacity is a key determinant for the cellular response to platinum (DDP) agents, DNA repair functional assays are required to study its relevance in DDP resistance. We set up a proximity ligation assay (PLA) to study the activity of nucleotide excision repair (NER) in patient derived ovarian carcinoma xenografts (PDXs) sensitive (S) and resistant (R) to DDP. Material and methods Patient derived xenografts from fresh ovarian carcinomas were recently established in our laboratory. DDP antitumour activity was evaluated in most of the PDXs. Mice were sacrificed when tumours reached 1,5–2 gr. Tumours were fixed in formalin and paraffin embedded (FFPE). PLA was performed on tumour slides, using DuolinkII reagents (Sigma-Aldrich) and following the manufacturer instructions. PLA detects the presence of the protein complexes ERCC1-XPF, that are quantified as foci per nucleus and represent a biomarker of NER activity. Images were acquired by Olympus Virtual Slider (Olympus) and analysed with ImageJ software. Statistical analysis was performed with GraphPad Prism7. Results and discussions Our xenobank comprises PDXs with different response to DDP: MNHOC266 and MNHOC230 are very sensitive to the drug, while MNHOC315 is resistant. We also obtained three sublines resistant to DDP (MNHOC124R, MNHOC124LPR and MNHOC239R) starting from sensitive PDXs (MNHOC124S, MNHOC124LPS and MNHOC239S), after several in vivo drug treatments. Statistically significant higher level of ERCC1-XPF foci could be observed in MNHOC124R and MNHOC124LPR as compared to their sensitive counterparts. No differences were observed between MNHOC239S and R PDXs, even if the number of ERCC1-XPF foci in MNHOC239S were statistically higher than the ones observed in MNHOC124S and in MNHOC124LPS. MNHOC266 and MNHOC230 showed levels of foci comparable to those of MNHOC124S and MNHOC124LPS. mRNA and protein levels of the different isoforms of ERCC1 and of XPF were not different among the PDXs studied. Conclusion PLA for the detection of ERCC1-XPF complexes was set up in FFPE xenograft tumour slides. These preliminary results highlight a possible link between DDP resistance and higher NER activity that need to be confirmed in a wider panel of PDXs. In addition, these data confirm the importance to develop functional assays to directly evaluate the activity of different DNA repair pathways to predict DDP activity

Potential role of interleukin-1 at the peri-ovulation stage in a species of placental viviparous reptile, the three-toed skink, Chalcides chalcides (squamata: scincidae)

We recently showed that interleukin-1 (IL-1) is secreted by the placenta of a species of squamate reptile, the three-toed skink, Chalcides chalcides. In this study, we used immunohistochemical techniques to investigate the expression of IL-1 (in the two isoforms, IL-1α and IL-1β) and its specific membrane receptor IL-1 RtI in uterine oviduct during the peri-implantation period. We found that both IL-1 and its receptor were expressed in uterine tissues before and after ovulation (in the pre-ovulatory stage, even before the yolk had formed in the ovary). However, while IL-1α was mostly localized in the uterine mesenchyme tissue, IL-1β and IL-1RtI were present in the uterine epithelium. Our data provide a further comparison between the reproduction of mammals and squamate reptiles