14,482 research outputs found

    Preterm pigs for preterm birth research: reasonably feasible

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    Preterm birth will disrupt the pattern and course of organ development, which may result in morbidity and mortality of newborn infants. Large animal models are crucial resources for developing novel, credible, and effective treatments for preterm infants. This review summarizes the classification, definition, and prevalence of preterm birth, and analyzes the relationship between the predicted animal days and one human year in the most widely used animal models (mice, rats, rabbits, sheep, and pigs) for preterm birth studies. After that, the physiological characteristics of preterm pig models at different gestational ages are described in more detail, including birth weight, body temperature, brain development, cardiovascular system development, respiratory, digestive, and immune system development, kidney development, and blood constituents. Studies on postnatal development and adaptation of preterm pig models of different gestational ages will help to determine the physiological basis for survival and development of very preterm, middle preterm, and late preterm newborns, and will also aid in the study and accurate optimization of feeding conditions, diet- or drug-related interventions for preterm neonates. Finally, this review summarizes several accepted pediatric applications of preterm pig models in nutritional fortification, necrotizing enterocolitis, neonatal encephalopathy and hypothermia intervention, mechanical ventilation, and oxygen therapy for preterm infants

    Influences on Expert Intelligibility Judgments of School-age Children's Speech

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    Speech-language pathologists (SLPs) make impressionistic intelligibility judgments as part of an evaluation of children for speech sound disorders. Despite the lack of formalization, it is an important measure of choice for SLPs, going beyond single-word standardized measures by using spontaneous speech to assess functional communication. However, spontaneous speech introduces sources of error and bias in the listener. This dissertation argues that impressionistic intelligibility judgments are influenced by listener-dependent factors due to their subjectivity. To identify potential sources of error and bias, speech data were collected from four school-aged child groups: typically developing monolingual, children with speech sound disorder, typically developing Spanish-English bilingual (i.e., an accent familiar to the study’s listeners), and typically developing Mam-English bilingual (i.e., an accent unfamiliar to the study’s listeners), in two school-age groups. Perceiver data were collected from two listener groups (i.e., expert [SLP] and lay). Listeners provided baseline measurements of lab-based intelligibility scores and comprehensibility ratings by orthographically transcribing and rating audio recordings of experimentally controlled utterances. Listeners also made impressionistic global intelligibility assessments after viewing video recordings of children’s spontaneous speech. Findings showed differences between expert’s and lay listener’s global intelligibility assessments however experts were no better than lay listeners at discerning between age and speaker groups. Of the four speaker groups, there was a significant effect of the Mam-English bilingual speaker group on global intelligibility assessments. Relationships were found between global intelligibility assessments and both the lab-based intelligibility measure and the comprehensibility rating, indicating impressionistic judgments tap into both speech signal features and the understandability of speech. Surprisingly, the age and linguistic ability of the child speakers were not significant factors on global intelligibility assessments, so perhaps listeners were making accommodations for these differences in their assessments. These findings indicate the need for increased training of SLPs to reduce error and bias in their speech intelligibility judgments, as well as the need for further research to improve its objectivity

    Living with erythropoietic protoporphyria:Bridging the gap between research and clinical practice

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    Studies on genetic and epigenetic regulation of gene expression dynamics

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    The information required to build an organism is contained in its genome and the first biochemical process that activates the genetic information stored in DNA is transcription. Cell type specific gene expression shapes cellular functional diversity and dysregulation of transcription is a central tenet of human disease. Therefore, understanding transcriptional regulation is central to understanding biology in health and disease. Transcription is a dynamic process, occurring in discrete bursts of activity that can be characterized by two kinetic parameters; burst frequency describing how often genes burst and burst size describing how many transcripts are generated in each burst. Genes are under strict regulatory control by distinct sequences in the genome as well as epigenetic modifications. To properly study how genetic and epigenetic factors affect transcription, it needs to be treated as the dynamic cellular process it is. In this thesis, I present the development of methods that allow identification of newly induced gene expression over short timescales, as well as inference of kinetic parameters describing how frequently genes burst and how many transcripts each burst give rise to. The work is presented through four papers: In paper I, I describe the development of a novel method for profiling newly transcribed RNA molecules. We use this method to show that therapeutic compounds affecting different epigenetic enzymes elicit distinct, compound specific responses mediated by different sets of transcription factors already after one hour of treatment that can only be detected when measuring newly transcribed RNA. The goal of paper II is to determine how genetic variation shapes transcriptional bursting. To this end, we infer transcriptome-wide burst kinetics parameters from genetically distinct donors and find variation that selectively affects burst sizes and frequencies. Paper III describes a method for inferring transcriptional kinetics transcriptome-wide using single-cell RNA-sequencing. We use this method to describe how the regulation of transcriptional bursting is encoded in the genome. Our findings show that gene specific burst sizes are dependent on core promoter architecture and that enhancers affect burst frequencies. Furthermore, cell type specific differential gene expression is regulated by cell type specific burst frequencies. Lastly, Paper IV shows how transcription shapes cell types. We collect data on cellular morphologies, electrophysiological characteristics, and measure gene expression in the same neurons collected from the mouse motor cortex. Our findings show that cells belonging to the same, distinct transcriptomic families have distinct and non-overlapping morpho-electric characteristics. Within families, there is continuous and correlated variation in all modalities, challenging the notion of cell types as discrete entities

    Ureilite meteorites and the unknown proto-planet: using EBSD to construct a geological history

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    The ureilites are a group of ultramafic achondrite meteorites composed primarily of olivine and pigeonite, with accessory minerals and a high abundance of carbon in the form of graphite and diamond. There are many hypotheses as to how the ureilite group formed, but the majority of authors are now in agreement that they represent a mantle restite of a now destroyed planetesimal that may have been as large as Mercury (Nabiei et al., 2018). This planetesimal was large enough for the ureilites to form through igneous processing, but not large enough to become a full planet. At some point, possibly within the first 10 million years (Rai et al., 2020) of its life the ureilite parent body (UPB) was subjected to a catastrophic impact which destroyed the planetesimal and created daughter asteroids which are the current parent bodies of the ureilites (Goodrich et al., 2015). This study aims to construct a comprehensive geological history of the samples using Electron Backscatter Diffraction (EBSD), Energy Dispersive Spectroscopy (EDS), Raman spectroscopy and geochemical data. Here we show using Raman peak Full Width Half Maximum (FWHM) data that the majority of diamonds present in the ureilite suite are formed through shock related processes. This is combined with the EBSD data and optical microscopy data to discuss a range of shock features present within the ureilites such as mosaicism. Various slip systems are shown to be activated across the samples indicating deformation occurred during a variety of temperature and pressure conditions throughout ureilite formation. Evidence of shear processes affecting the majority of the samples studied is also presented using the EBSD datasets. A proposed geological history is presented to tie shock and shear features together. Our results agree with recent studies about diamond formation (Nestola et al., 2020) on the UPB which goes some way to negating the need for a large planetesimal to be required in order to explain ureilite formation

    Key technologies for safe and autonomous drones

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    Drones/UAVs are able to perform air operations that are very difficult to be performed by manned aircrafts. In addition, drones' usage brings significant economic savings and environmental benefits, while reducing risks to human life. In this paper, we present key technologies that enable development of drone systems. The technologies are identified based on the usages of drones (driven by COMP4DRONES project use cases). These technologies are grouped into four categories: U-space capabilities, system functions, payloads, and tools. Also, we present the contributions of the COMP4DRONES project to improve existing technologies. These contributions aim to ease drones’ customization, and enable their safe operation.This project has received funding from the ECSEL Joint Undertaking (JU) under grant agreement No 826610. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and Spain, Austria, Belgium, Czech Republic, France, Italy, Latvia, Netherlands. The total project budget is 28,590,748.75 EUR (excluding ESIF partners), while the requested grant is 7,983,731.61 EUR to ECSEL JU, and 8,874,523.84 EUR of National and ESIF Funding. The project has been started on 1st October 2019

    Waiting Nets: State Classes and Taxonomy

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    In time Petri nets (TPNs), time and control are tightly connected: time measurement for a transition starts only when all resources needed to fire it are available. Further, upper bounds on duration of enabledness can force transitions to fire (this is called urgency). For many systems, one wants to decouple control and time, i.e. start measuring time as soon as a part of the preset of a transition is filled, and fire it after some delay \underline{and} when all needed resources are available. This paper considers an extension of TPN called waiting nets that dissociates time measurement and control. Their semantics allows time measurement to start with incomplete presets, and can ignore urgency when upper bounds of intervals are reached but all resources needed to fire are not yet available. Firing of a transition is then allowed as soon as missing resources are available. It is known that extending bounded TPNs with stopwatches leads to undecidability. Our extension is weaker, and we show how to compute a finite state class graph for bounded waiting nets, yielding decidability of reachability and coverability. We then compare expressiveness of waiting nets with that of other models w.r.t. timed language equivalence, and show that they are strictly more expressive than TPNs

    Endogenous measures for contextualising large-scale social phenomena: a corpus-based method for mediated public discourse

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    This work presents an interdisciplinary methodology for developing endogenous measures of group membership through analysis of pervasive linguistic patterns in public discourse. Focusing on political discourse, this work critiques the conventional approach to the study of political participation, which is premised on decontextualised, exogenous measures to characterise groups. Considering the theoretical and empirical weaknesses of decontextualised approaches to large-scale social phenomena, this work suggests that contextualisation using endogenous measures might provide a complementary perspective to mitigate such weaknesses. This work develops a sociomaterial perspective on political participation in mediated discourse as affiliatory action performed through language. While the affiliatory function of language is often performed consciously (such as statements of identity), this work is concerned with unconscious features (such as patterns in lexis and grammar). This work argues that pervasive patterns in such features that emerge through socialisation are resistant to change and manipulation, and thus might serve as endogenous measures of sociopolitical contexts, and thus of groups. In terms of method, the work takes a corpus-based approach to the analysis of data from the Twitter messaging service whereby patterns in users’ speech are examined statistically in order to trace potential community membership. The method is applied in the US state of Michigan during the second half of 2018—6 November having been the date of midterm (i.e. non-Presidential) elections in the United States. The corpus is assembled from the original posts of 5,889 users, who are nominally geolocalised to 417 municipalities. These users are clustered according to pervasive language features. Comparing the linguistic clusters according to the municipalities they represent finds that there are regular sociodemographic differentials across clusters. This is understood as an indication of social structure, suggesting that endogenous measures derived from pervasive patterns in language may indeed offer a complementary, contextualised perspective on large-scale social phenomena

    Circadian variations in aortic stiffness, sympathetic vasoconstriction, and post-ischemic vasodilation in adults with and without type 2 diabetes.

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    The current literature reveals a lack of information on the circadian variations of some important cardiovascular risk factors related to the work of the heart or the capacity to provide blood and oxygen to various tissues. These factors include aortic stiffness, peripheral vasoconstrictor responsiveness, and post-ischemic vasodilation capacity. Furthermore, it is not clear whether the impact of an external stressor capable of activating the sympathetic nervous system could have greater repercussions on the cardiovascular system in the morning than in the evening. Given the higher incidence of acute cardiovascular events in the morning than in the evening, the studies undertaken in this thesis aim to investigate the circadian variations of these factors that are linked to cardiovascular risk, both at rest and during acute activation of the sympathetic nervous system. Type 2 diabetes (T2DM) is a condition that induces deleterious changes in cardiovascular function, impacting cardiovascular mortality and morbidity. Thus, the impact of diabetes will be evaluated. As a secondary purpose, considering the sex differences in the incidence and prognosis of cardiovascular disease, the effect of sex will be evaluated. Aortic stiffness proved not to be increased in the morning compared to the evening at specific times when the cardiovascular risk is significantly different, both at rest and during sympathetic activation. However, while healthy older women show similar aortic stiffness values compared to their male counterparts during acute stress, older women with T2DM reported greater aortic stiffness compared to men with T2DM. The post-ischemic forearm vasodilation is blunted in the morning compared to the evening in healthy elderly and such an attenuated vasodilation capacity impairs blood flow supply towards the ischemic area. The presence of T2DM does not affect vasodilation capacity and reactive hyperemia, but induces circadian variations in arterial pressure. The peripheral vasoconstriction triggered by a standardized sympathetic stressor is similar between morning and evening, regardless of the presence of T2DM and reduced baseline vascular conductance values in the morning. However, the peripheral vasoconstriction responsiveness is blunted in individuals with T2DM than in healthy ones as sympathetic activation induces vasodilation on the contralateral forearm in individuals with T2DM and vasoconstriction in healthy age-matched subjects. This finding highlights a neurovascular response to an external stressor altered by T2DM. Taken together, our findings suggest that the baseline state of constriction of the peripheral vascular tissue is greater in the morning than in the evening, but this fact is not due to greater sympathetic vasoconstriction responsiveness in the morning. Higher morning vasoconstriction at baseline however affects the capacity of a vascular tissue to dilate and, in turn, to supply blood to an ischemic tissue. Similar sympathetic vasoconstriction responsiveness between morning and evening is a likely factor explaining similar or lower values of central artery stiffness in the morning than in the evening, not only at rest but also during sympathetic excitation. Paradoxically, adults with T2DM report an increase in sympathetic-mediated dilatation capacity on the vascular tissue, which might be a defense mechanism that allows to reduce the central pressor response during sympathetic excitation
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