State of the field: digital history

Computing and the use of digital sources and resources is an everyday and essential practice in current academic scholarship. The present article gives a concise overview of approaches and methods within digital historical scholarship, focussing on the question: How have the Digital Humanities evolved and what has that evolution brought to historical scholarship? We begin by discussing techniques in which data are generated and machine searchable, such as OCR/HTR, born-digital archives, computer vision, scholarly editions, and Linked Data. In the second section, we provide examples of how data is made more accessible through quantitative text and network analysis. We close with a section on the need for hermeneutics and data-awareness in digital historical scholarship. The technologies described in this article have had varying degrees of effect on historical scholarship, usually in indirect ways. For example, technologies such as OCR and search engines may not be directly visible in a historical argument; however, these technologies do shape how historians interact with sources and whether sources can be accessed at all. It is with this article that we aim to start to take stock of the digital approaches and methods used in historical scholarship which may serve as starting points for scholars to understand the digital turn in the field and how and when to implement such approaches in their work

The Perfect Data-Marriage

There is a growing recognition in transitional justice research of the crucial significance of context-appropriate measures of justice practices and needs, which account for the diversity, locality, and complexity of individuals’ experiences of the past. In this perspective, this paper highlights the significance of oral history collections for exploring pluralistic understandings of the personal past and their relation to symbolic justice practices and needs. We argue that their audio-visual dimension and multi-layered nature makes them a unique qualitative data source that can contribute to a more realistic assessment of justice concerns in transitional settings. As tools of social dialogue and inclusive justice, they are also valuable means to promote the mutual acceptance and recognition of suffering and responsibility. We demonstrate how findings based on the analysis of survey data collected in Bosnia-Herzegovina (BiH) can be enriched by the exploration of oral history narratives from a dataset collected in BiH

po 130 ser235 residue drives eif6 oncogenic activity in npm alk induced t cell lymphomagenesis

Introduction Dysregulation of mRNA translational control in cancer leads to cell transformation, metabolic reprogramming and angiogenesis. eIF6 is an oncogenic translation factor, which regulates the initiation phase of translation acting on 60S availability in the cytoplasm and controlling active 80S complex formation. eIF6 activation is mTORC1-independent and driven by PKCβ mediated phosphorylation on Ser235. An increment of eIF6 expression is reported in several cancer cell lines and human tumours, due to amplification or overexpression. In mice, eIF6 haploinsufficiency blocks Myc-driven lymphomagenesis. Intriguingly, high levels of PKC and eIF6 are found in T-cell lymphomas. In particular, in Anaplastic Large Cell Lymphoma (ALCL) eIF6 is overexpressed and hyperactivated. Material and methods Here, we aimed to define the role of eIF6 phosphorylation in NPM-ALK mediated T-cell lymphomagenesis, combining multidisciplinary studies on murine and cellular models. We used a conditional eIF6 SA KI mouse model in which Ser235 is replaced by an Ala. Results and discussions First, we addressed the effect of eIF6 mutated protein expression in all tissues: homozygosity is lethal after gastrulation while heterozygous mice are viable but resistant to NPM-ALK driven lymphomagenesis. Then, we investigated the role of Ser235 phosphorylation specifically in T-cell lineage, crossing eIF6 SA KI mice with CD4-Cre mice. Physiological T-cell development and subsets composition are not affected by the eIF6 mutated protein. In cancer, eIF6 SA/SA CD4-Cre NPM-ALK mice have a significant increase in survival time, compared to wt with a delay in the appearance of lymphoma up to 6 months. Histological analysis and ex vivo cultures confirm the delay in disease development. eIF6 SA/SA CD4-Cre NPM-ALK thymocytes are smaller respect to wt counterparts and show a striking senescence-like phenotype in vitro . Similarly, in vitro generated eIF6 SA/SA MEFs show a markedly reduced proliferation and increased SA β-gal positivity. This phenotype is completely rescued by transducing eIF6 wild-type, but not by eIF6 SA . Currently, we are investigating the molecular mechanisms by which eIF6 phosphorylation affects ALK-induced malignancy and whether it may modulate premature cell senescence, thus establishing an effective barrier to T-cell lymphomagenesis. Conclusion Our work demonstrates for the first time that eIF6 phosphorylation plays an essential role in mammals development, cell homeostasis and is rate-limiting for T-cell lymphomagenesis in vivo

The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks

Regular endurance training improves muscle oxidative capacity and reduces the risk of age-related disorders. Understanding the molecular networks underlying this phenomenon is crucial. Here, by exploiting the power of computational modeling, we show that endurance training induces profound changes in gene regulatory networks linking signaling and selective control of translation to energy metabolism and tissue remodeling. We discovered that knockdown of the mTOR-independent factor Eif6, which we predicted to be a key regulator of this process, affects mitochondrial respiration efficiency, ROS production, and exercise performance. Our work demonstrates the validity of a data-driven approach to understanding muscle homeostasis

CryoSat Ice Baseline-D validation and evolutions

The ESA Earth Explorer CryoSat-2 was launched on 8 April 2010 to monitor the precise changes in the thickness of terrestrial ice sheets and marine floating ice. To do that, CryoSat orbits the planet at an altitude of around 720 km with a retrograde orbit inclination of 92∘ and a quasi repeat cycle of 369 d (30 d subcycle). To reach the mission goals, the CryoSat products have to meet the highest quality standards to date, achieved through continual improvements of the operational processing chains. The new CryoSat Ice Baseline-D, in operation since 27 May 2019, represents a major processor upgrade with respect to the previous Ice Baseline-C. Over land ice the new Baseline-D provides better results with respect to the previous baseline when comparing the data to a reference elevation model over the Austfonna ice cap region, improving the ascending and descending crossover statistics from 1.9 to 0.1 m. The improved processing of the star tracker measurements implemented in Baseline-D has led to a reduction in the standard deviation of the point-to-point comparison with the previous star tracker processing method implemented in Baseline-C from 3.8 to 3.7 m. Over sea ice, Baseline-D improves the quality of the retrieved heights inside and at the boundaries of the synthetic aperture radar interferometric (SARIn or SIN) acquisition mask, removing the negative freeboard pattern which is beneficial not only for freeboard retrieval but also for any application that exploits the phase information from SARIn Level 1B (L1B) products. In addition, scatter comparisons with the Beaufort Gyre Exploration Project (BGEP; https://www.whoi.edu/beaufortgyre, last access: October 2019) and Operation IceBridge (OIB; Kurtz et al., 2013) in situ measurements confirm the improvements in the Baseline-D freeboard product quality. Relative to OIB, the Baseline-D freeboard mean bias is reduced by about 8 cm, which roughly corresponds to a 60 % decrease with respect to Baseline-C. The BGEP data indicate a similar tendency with a mean draft bias lowered from 0.85 to −0.14 m. For the two in situ datasets, the root mean square deviation (RMSD) is also well reduced from 14 to 11 cm for OIB and by a factor of 2 for the BGEP. Observations over inland waters show a slight increase in the percentage of good observations in Baseline-D, generally around 5 %–10 % for most lakes. This paper provides an overview of the new Level 1 and Level 2 (L2) CryoSat Ice Baseline-D evolutions and related data quality assessment, based on results obtained from analyzing the 6-month Baseline-D test dataset released to CryoSat expert users prior to the final transfer to operations

D-mannose suppresses macrophage IL-1β production

D-mannose is a monosaccharide approximately a hundred times less abundant than glucose in human blood. Previous studies demonstrated that supraphysiological levels of D-mannose inhibit tumour growth and stimulate regulatory T cell differentiation. It is not known whether D-mannose metabolism affects the function of non-proliferative cells, such as inflammatory macrophages. Here, we show that D-mannose suppresses LPS-induced macrophage activation by impairing IL-1β production. In vivo, mannose administration improves survival in a mouse model of LPS-induced endotoxemia as well as decreases progression in a mouse model of DSS-induced colitis. Phosphomannose isomerase controls response of LPS-activated macrophages to D-mannose, which impairs glucose metabolism by raising intracellular mannose-6-phosphate levels. Such alterations result in the suppression of succinate-mediated HIF-1α activation, imposing a consequent reduction of LPS-induced Il1b expression. Disclosing an unrecognized metabolic hijack of macrophage activation, our study points towards safe D-mannose utilization as an effective intervention against inflammatory conditions