Matura Evaluation Experiment Based on Human Evaluation of Machine Translation

Abstract—A Web-based system for human evaluation of machine translation is presented in this paper. The system is based on comprehension tests similar to the ones used in Polish matura (secondary school-leaving) examinations. The results of preliminary experiments for Polish-English and English-Polish machine translation evaluation are presented and discussed. I

Comprehensive analysis of synthetic learning applied to neonatal brain MRI segmentation

Brain segmentation from neonatal MRI images is a very challenging task due to large changes in the shape of cerebral structures and variations in signal intensities reflecting the gestational process. In this context, there is a clear need for segmentation techniques that are robust to variations in image contrast and to the spatial configuration of anatomical structures. In this work, we evaluate the potential of synthetic learning, a contrast-independent model trained using synthetic images generated from the ground truth labels of very few subjects.We base our experiments on the dataset released by the developmental Human Connectome Project, for which high-quality T1- and T2-weighted images are available for more than 700 babies aged between 26 and 45 weeks post-conception. First, we confirm the impressive performance of a standard Unet trained on a few T2-weighted volumes, but also confirm that such models learn intensity-related features specific to the training domain. We then evaluate the synthetic learning approach and confirm its robustness to variations in image contrast by reporting the capacity of such a model to segment both T1- and T2-weighted images from the same individuals. However, we observe a clear influence of the age of the baby on the predictions. We improve the performance of this model by enriching the synthetic training set with realistic motion artifacts and over-segmentation of the white matter. Based on extensive visual assessment, we argue that the better performance of the model trained on real T2w data may be due to systematic errors in the ground truth. We propose an original experiment combining two definitions of the ground truth allowing us to show that learning from real data will reproduce any systematic bias from the training set, while synthetic models can avoid this limitation. Overall, our experiments confirm that synthetic learning is an effective solution for segmenting neonatal brain MRI. Our adapted synthetic learning approach combines key features that will be instrumental for large multi-site studies and clinical applications

Aerospace Medicine and Biology: A continuing bibliography with indexes (supplement 133)

This special bibliography lists 276 reports, articles, and other documents introduced into the NASA Scientific and Technical Information System in September 1974

Doxorubicin-induced DNA Damage Causes Extensive Ubiquitination of Ribosomal Proteins Associated with a Decrease in Protein Translation

Protein posttranslational modifications (PTMs) play a central role in the DNA damage response. In particular, protein phosphorylation and ubiquitination have been shown to be essential in the signaling cascade that coordinates break repair with cell cycle progression. Here, we performed whole-cell quantitative proteomics to identify global changes in protein ubiquitination that are induced by DNA double-strand breaks. In total, we quantified more than 9,400 ubiquitin sites and found that the relative abundance of similar to 10% of these sites was altered in response to DNA double-strand breaks. Interestingly, a large proportion of ribosomal proteins, including those from the 40S as well as the 60S subunit, were ubiquitinated in response to DNA damage. In parallel, we discovered that DNA damage leads to the inhibition of ribosome function. Taken together, these data uncover the ribosome as a major target of the DNA damage response.This work is funded by a TOP-GO grant from the Netherlands Organization for Scientific Research (NWO ZonMW 912100651 to R.H.M., S.M., and V.A.H.). I.G.S. was supported with a postdoctoral fellowship from the Basque Country Government (Spain). We thank Christian Frese and Teck Yew Low for fruitful discussions. We also thank Teck Yew Low for submitting the raw files and annotated spectra to PRIDE. We thank Fabricio Loayza-Puch for his technical help with the sucrose gradients

Progress in scaffold-free bioprinting for cardiovascular medicine

Biofabrication of tissue analogues is aspiring to become a disruptive technology capable to solve standing biomedical problems, from generation of improved tissue models for drug testing to alleviation of the shortage of organs for transplantation. Arguably, the most powerful tool of this revolution is bioprinting, understood as the assembling of cells with biomaterials in three-dimensional structures. It is less appreciated, however, that bioprinting is not a uniform methodology, but comprises a variety of approaches. These can be broadly classified in two categories, based on the use or not of supporting biomaterials (known as "scaffolds," usually printable hydrogels also called "bioinks"). Importantly, several limitations of scaffold-dependent bioprinting can be avoided by the "scaffold-free" methods. In this overview, we comparatively present these approaches and highlight the rapidly evolving scaffold-free bioprinting, as applied to cardiovascular tissue engineering

Characterization of Human Pubertal Timing Gene VGLL3 in Zebrafish Development

Puberty is a process of physiological changes, through which an immature individual becomes sexually mature. In humans, timing of puberty is highly variable within and between sexes and populations. Timing of puberty represents a complex trait, which is controlled both genetically and environmentally. Precocious pubertal timing is associated with development of metabolic diseases later in life, such as obesity and diabetes, and other disorders as ovarian and testicular cancer. Despite the estimated high heritability (50-80%) of pubertal timing, its genetic background is still poorly understood. Recently, the genome-wide association studies (GWASs) revealed many novel pubertal timing associated loci. Nevertheless, molecular mechanisms behind these associations remain elusive. This thesis focused on gene vestigial-like family member 3 (VGLL3), which is associated with pubertal timing in humans and maturation in Atlantic salmon (Salmo salar). Since the main physical structures, such as the hypothalamus and the pituitary gland, needed in reaching puberty are evolutionary conserved and start to develop in vertebrates during embryogenesis, the aim was to study the expression pat-terns and role of vgll3 in zebrafish (Danio rerio) during this period. In order to localize expression patterns of the vgll3 gene in zebrafish embryos, a whole-mount in situ RNA hybridization (ISH) was performed. mRNA overexpression and morpholino oligonucleotide (MO) knockdown techniques were used to alter the vgll3 gene expression levels in 0-5 dpf zebrafish. The combined injections of both mRNA and MO were performed to validate MO specificity. The ISH experiment showed the expression patterns in 0-1 dpf embryos. The expression was ubiquitous up to 6 hours post fertilization becoming more localized to specific regions in the head and trunk of the embryos during the later stages. Altering vgll3 expression with high concentrations of synthetic mRNA or MO lead to phenotypical abnormalities such as shortened and curved body axis, pericardial and yolk sack edemas, deformed heads and eyes. However, it remained unclear if these malformations appear only due to the alteration of vgll3 expression levels. The results suggest that vgll3 may play an important role in the embryonic development. However, the study does not show that vgll3 has impacts on the pubertal timing in vertebrates by affecting the development of the structures required for sexual maturation.Murrosikä eli puberteetti on kehitysvaihe, jolloin yksilö kehittyy sukukypsäksi. Murrosiän ajoittuminen ihmisillä vaihtelee paljon sekä sukupuolen sisällä että sukupuolten ja populaatioiden välillä. Murrosiän ajoittuminen on monitekijäinen ominaisuus eli sekä perimä että ympäristötekijät vaikuttavat ajoittumiseen. Poikkeuksellisen varhainen murrosikä on liitetty erilaisiin aineenvaihduntasairauksiin kuten lihavuuteen ja II-tyypin diabetekseen sekä muihin sairauksiin kuten munasarja- ja kivessyöpään. Vaikka perinnöllisten tekijöiden arvioidaan selittävän n. 50-80% murrosiän ajoittumisen vaihtelusta, murrosiän geneettistä taustaa ei kuitenkaan tunneta kovin hyvin. Genominlaajuisissa assosiaatiotutkimuksissa on hiljattain selvitetty murrosiän ajoittumiseen vaikut-tavia geneettisiä lokuksia. Yksi näistä assosiaatioista oli geeni vestigial-like family member 3 (VGLL3). Tässä pro gradu -työssä keskityttiin selvittämään mekanismeja, joilla sukukypsyyden ajoittumiseen niin ihmisillä kuin lohella (Salmo salar) vaikuttava VGLL3-geeni toimii. Koska murrosiän kannalta tärkeimmät fyysiset rakenteet, mukaan lukien hypotalamus ja aivolisäke, muodostuvat jo alkionkehityksen aikana, ja nämä rakenteet ovat säilyneet evoluutiossa kaikilla selkärankaisilla, tavoitteena oli tutkia vgll3:n ilmentymistä ja mahdollista kehityksellistä roolia seeprakalan alkioilla. Geenin ilmentymisen eli ekspression paikantamiseksi seeprakalan alkioissa on tässä työssä käytetty in situ-RNA -hybridisaatiotekniikkaa (ISH). Lisäksi geenin roolia on tutkittu yliekspressio- ja morfoliino-oligonukleotidi (MO)-knockdown -tekniikoilla, joiden avulla vgll3:n koodaaman proteiinin tuottoa on pyritty lisäämään ja hiljentämään muutaman päivän ikäisissä seeprakaloissa. MO:n ja synteettisen mRNA:n yhteisinjektiolla eli ns. rescue-kokeella on pyritty selvittämään johtuvatko havaitut fenotyypit nimenomaan vgll3:n expressiotason muutoksista. ISH-kokeessa havaittiin vgll3:n ilmentyvän jo 0-1-päiväisillä alkioilla. Alle seitsemän tunnin ikäisillä alkioilla vgll3-mRNA:ta oli havaittavissa kaikissa soluissa, kun taas siitä vanhemmilla alkioilla vgll3:n ilmentyminen paikantui selkeästi rajattuihin kohtiin pään ja rungon alueella. Korkeat MO:n ja mRNA:n annokset geeniekspression muuttamiseksi varhaisissa alkioissa johtivat selkeisiin poikkeavuuksiin mukaan lukien lyhyeksi ja käyräksi jäänyt runkoakseli, sydänpussin ja ruskuaispussin turvotus sekä epämuodostunut pää ja silmät. Tutkimuksessa jäi kuitenkin avoimeksi, johtuivatko nämä tulokset yksinomaan vgll3:n ekspressiotason muutoksista. Tutkimuksen tulosten perusteella voidaan olettaa, että vgll3:lla on mahdollisesti tärkeä rooli alkionkehityksessä. Tutkimuksessa ei kuitenkaan pystytty osoittamaan vgll3:n liittyvän selkärankaisten sukukyp-syyden ajoittumiseen vaikuttamalla tunnettujen murrosikään liitettyjen rakenteiden, kuten hypotalamuksen, kehitykseen

The art and architecture of mathematics education: a study in metaphors

This chapter presents the summary of a talk given at the Eighth European Summer University, held in Oslo in 2018. It attempts to show how art, literature, and history, can paint images of mathematics that are not only useful but relevant to learners as they can support their personal development as well as their appreciation of mathematics as a discipline. To achieve this goal, several metaphors about and of mathematics are explored

Dynamics of dendritic cell maturation are identified through a novel filtering strategy applied to biological time-course microarray replicates

<p>Abstract</p> <p>Background</p> <p>Dendritic cells (DC) play a central role in primary immune responses and become potent stimulators of the adaptive immune response after undergoing the critical process of maturation. Understanding the dynamics of DC maturation would provide key insights into this important process. Time course microarray experiments can provide unique insights into DC maturation dynamics. Replicate experiments are necessary to address the issues of experimental and biological variability. Statistical methods and averaging are often used to identify significant signals. Here a novel strategy for filtering of replicate time course microarray data, which identifies consistent signals between the replicates, is presented and applied to a DC time course microarray experiment.</p> <p>Results</p> <p>The temporal dynamics of DC maturation were studied by stimulating DC with poly(I:C) and following gene expression at 5 time points from 1 to 24 hours. The novel filtering strategy uses standard statistical and fold change techniques, along with the consistency of replicate temporal profiles, to identify those differentially expressed genes that were consistent in two biological replicate experiments. To address the issue of cluster reproducibility a consensus clustering method, which identifies clusters of genes whose expression varies consistently between replicates, was also developed and applied. Analysis of the resulting clusters revealed many known and novel characteristics of DC maturation, such as the up-regulation of specific immune response pathways. Intriguingly, more genes were down-regulated than up-regulated. Results identify a more comprehensive program of down-regulation, including many genes involved in protein synthesis, metabolism, and housekeeping needed for maintenance of cellular integrity and metabolism.</p> <p>Conclusions</p> <p>The new filtering strategy emphasizes the importance of consistent and reproducible results when analyzing microarray data and utilizes consistency between replicate experiments as a criterion in both feature selection and clustering, without averaging or otherwise combining replicate data. Observation of a significant down-regulation program during DC maturation indicates that DC are preparing for cell death and provides a path to better understand the process. This new filtering strategy can be adapted for use in analyzing other large-scale time course data sets with replicates.</p