Improving the translation environment for professional translators

When using computer-aided translation systems in a typical, professional translation workflow, there are several stages at which there is room for improvement. The SCATE (Smart Computer-Aided Translation Environment) project investigated several of these aspects, both from a human-computer interaction point of view, as well as from a purely technological side. This paper describes the SCATE research with respect to improved fuzzy matching, parallel treebanks, the integration of translation memories with machine translation, quality estimation, terminology extraction from comparable texts, the use of speech recognition in the translation process, and human computer interaction and interface design for the professional translation environment. For each of these topics, we describe the experiments we performed and the conclusions drawn, providing an overview of the highlights of the entire SCATE project

Disease modelling of GRN-related frontotemporal dementia using patient-derived and engineered stem cells

Frontotemporal dementia (FTD) is a neurodegenerative disease, leading to behavioral changes and language difficulties. Unlike other forms of dementia, FTD generally affects younger people and is heritable in many cases, with mutations in three genes (GRN, MAPT and C9orf72) explaining the majority of genetic cases. Autosomal dominant loss-of-function mutations in progranulin (GRN) induce haploinsufficiency of the protein and are associated with up to one third of all genetic FTD cases worldwide. However, in the rare event of homozygous loss of GRN, patients present with the strikingly different phenotype of neuronal ceroid lipofuscinosis. The study of GRN mutations has been hampered by the lack of overt signs of neurodegeneration in heterozygous Grn rodent models. Induced pluripotent stem cell (iPSC) technology offers an interesting alternative to create mutation-specific models and investigate the effects of GRN haploinsufficiency. In this manuscript, I describe the development a series of genome engineered hiPSC models that enable further study of the specific contribution of the GRN mutation to GRN-linked neurodegeneration. I seamlessly inserted the GRNIVS1+5G>C gene mutation into a normal donor iPSC line and created patient iPSC lines that conditionally overexpress a copy of the GRN gene with the aim to create a flexible, inducible correction of the GRN haploinsufficiency. Functional characterization of patient-derived GRN haploinsufficient iPSC, revealed possible cytoskeletal dysfunction. Transcriptome analysis of patient-derived and engineered GRN mutant neuronal progeny supported this possibility by revealing a disease-related transcriptional signature of reduced expression of extracellular matrix and cytoskeletal components. Investigating patient-derived and genome engineered GRNIVS1+5G>C PSC and cortical neurons, therefore unequivocally links disease related phenotypes to GRN haploinsufficiency. A key feature of neurons, is their electrophysiological activity. Investigating electrophysiological activity by standard methods however, is time-consuming and restricted in throughput. With the aim to improve maturation of neuronal cultures, I examined the effect of nanotopography on neuronal PSC progeny and it's applicability in microelectrode arrays (MEA). This lead to the development of a novel tool to investigate neurodegeneration.status: publishe

Recent advances in lineage differentiation from stem cells: hurdles and opportunities?

Pluripotent stem cells have the property of long-term self-renewal and the potential to give rise to descendants of the three germ layers and hence all mature cells in the human body. Therefore, they hold the promise of offering insight not only into human development but also for human disease modeling and regenerative medicine. However, the generation of mature differentiated cells that closely resemble theircounterparts remains challenging. Recent advances in single-cell transcriptomics and computational modeling of gene regulatory networks are revealing a better understanding of lineage commitment and are driving modern genome editing approaches. Additional modification of the chemical microenvironment, as well as the use of bioengineering tools to recreate the cellular, extracellular matrix, and physical characteristics of the niche wherein progenitors and mature cells reside, is now being used to further improve the maturation and functionality of stem cell progeny.status: publishe

Recent advances in lineage differentiation from stem cells: hurdles and opportunities? [version 1; referees: 2 approved]

Pluripotent stem cells have the property of long-term self-renewal and the potential to give rise to descendants of the three germ layers and hence all mature cells in the human body. Therefore, they hold the promise of offering insight not only into human development but also for human disease modeling and regenerative medicine. However, the generation of mature differentiated cells that closely resemble their in vivo counterparts remains challenging. Recent advances in single-cell transcriptomics and computational modeling of gene regulatory networks are revealing a better understanding of lineage commitment and are driving modern genome editing approaches. Additional modification of the chemical microenvironment, as well as the use of bioengineering tools to recreate the cellular, extracellular matrix, and physical characteristics of the niche wherein progenitors and mature cells reside, is now being used to further improve the maturation and functionality of stem cell progeny

The Characteristic Eye Movement Disorder of RFC1-Linked CANVAS

status: publishe

High spatial resolution geochemistry and textural characteristics of 'microtektite' glass spherules in proximal Cretaceous-Paleogene sections: insights into glass alteration patterns and precursor melt lithologies

Using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), we have conducted spatially resolved trace element analysis on fresh, unaltered microtektite glasses linked to the Cretaceous-Paleogene (K-Pg) boundary Chicxulub crater and on their surrounding alteration phases. This unique approach offers the opportunity to study in situ and at high spatial resolution both the mixing of different target lithologies and the variation of the major and trace element budget during the alteration process. In addition, two-dimensional element distribution maps reveal important geochemical information beyond the capabilities of single spot laser drilling. Glasses from two localities in opposite quadrants from the source crater were studied. At the Beloc locality (Haiti), the glass population is dominated by the presence of yellow high-Ca glass and black andesitic glass formed by admixture of carbonate/dolomite/anhydrite platform lithologies with crystalline basement. These glasses alter according to the well-established hydration-palagonitization model postulated for mafic volcanic glasses. REEs become progressively leached from the glass to below the detection limit for the applied spot size, while immobile Zr, Hf, Nb, and Ta passively accumulate in the process exhibiting both inter-element ratios and absolute concentrations similar to those for the original glass. In contrast, The Arroyo El Mimbral locality (NE Mexico) is characterized by abundant green glass fragments high in Si, Al and alkalis, and low in Mg, Ca, Fe. Low Si black glass is less abundant though similar in composition to the black glass variety at Beloc. The alteration pattern of high-Si, Al green glass at the Mimbral locality is more complex, including numerous competing reaction processes (ion-exchange, hydration, dissolution, and secondary mineral precipitation) generally controlled by the pH and composition of the surrounding fluid. All green, high-Si, Al glasses are hydrated and variably enriched in Sr, Ba, and Cs, indicating preferred adsorption from seawater during hydration. Despite the onset of ion-exchange reactions, which only seem to have affected the alkalis, the trace element composition of the green high-Si, Al glass is still largely representative of the original melt composition. Refining the geochemical signature of (altered) melt lithologies may advance our current understanding of glass stability in the natural environment and provide insight into the origin and emplacement of ejecta material during crater formation

Topographical Guidance of PSC-Derived Cortical Neurons

© 2018 Joke Terryn et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background and Aims: Human pluripotent stem cell- (PSC-) derived neurons are increasingly used in the study of neurodevelopmental and neurodegenerative diseases. Electrophysiological activity is a crucial and defining function of these neurons. Patch clamping and the more recently developed multielectrode arrays are used to evaluate this complex function. In this study, we assess the effect of topography on PSC-derived neurons as a baseline for the development of next-generation silicon oxide substrates (in direct relation to MEA fabrication) that integrate topography as a means to guide network formation and stimulate differentiation. Methods: Human PSC was differentiated towards cortical neurons and seeded on a silicon micropatterned substrate to screen for topographic guidance and improved neurite outgrowth. We next developed customized micropillar and microgroove substrates to further assess the effect of topography on human cortical neurons. Immunocytochemistry and morphological analyses were used to track neuron differentiation and guidance. Results: Microgroove and micropillar substrates appeared to support the differentiation of human stem cell-derived cortical neurons, promoted neurite outgrowth, and facilitated contact guidance. In contrast to flat surfaces, topography also appeared to limit the number of NESTIN positive neuronal progenitor cells present in the culture. Conclusion: We describe the topographical preferences of human PSC-derived cortical neurons, on neurite outgrowth and guidance. Embedding topography in silicon substrates may be an effective approach to direct and improve neuronal network formation. We propose to integrate topography in multielectrode arrays as a practical method to shape the neuro-electronic interface.status: publishe

Ni-rich spinels and platinum group element nuggets condensed from a Late Archaean impact vapour cloud

Deciphering Earthʼs impact history before ∼2 Ga relies heavily on the lunar record and terrestrial spherule layers, which are distal ejecta from large impacts. This study focuses on the Paraburdoo and Reivilo spherule layers in Western Australia and South Africa respectively, that were probably formed by one impact around 2.57 Ga. Both layers contain an aggregate thickness of ∼2 cm of spherules, known as microkrystites. These spherules are up to ∼0.6 mm in diameter and crystallized during flight, but were diagenetically replaced by K-feldspar and phlogopite with remarkable textural retention. Unlike any other Archaean layer, except for the 3.2 Ga S3 layer in the Barberton greenstone belt, the Paraburdoo and Reivilo spherules contain Ni-rich spinel crystals and high concentrations of meteoritic material (up to 357 ng g−1 Ir for bulk samples of several gram). These exceptional characteristics shed new light on the distribution of the meteoritic component carrier phases (metallic alloys dispersed in the pristine glass) and the processes involved in impact spherule formation and secondary alteration

Ni-rich spinels and platinum group element nuggets condensed from a Late Archaean impact vapour cloud

Deciphering Earthʼs impact history before ∼2 Ga relies heavily on the lunar record and terrestrial spherule layers, which are distal ejecta from large impacts. This study focuses on the Paraburdoo and Reivilo spherule layers in Western Australia and South Africa respectively, that were probably formed by one impact around 2.57 Ga. Both layers contain an aggregate thickness of ∼2 cm of spherules, known as microkrystites. These spherules are up to ∼0.6 mm in diameter and crystallized during flight, but were diagenetically replaced by K-feldspar and phlogopite with remarkable textural retention. Unlike any other Archaean layer, except for the 3.2 Ga S3 layer in the Barberton greenstone belt, the Paraburdoo and Reivilo spherules contain Ni-rich spinel crystals and high concentrations of meteoritic material (up to 357 ng g−1 Ir for bulk samples of several gram). These exceptional characteristics shed new light on the distribution of the meteoritic component carrier phases (metallic alloys dispersed in the pristine glass) and the processes involved in impact spherule formation and secondary alteration