103 research outputs found
Pathophysiology of Pediatric Diffuse Interstitial Lung Diseases of Genetic or Presumed Genetic Origin
No full textLes pneumopathies interstitielles diffuses (PID) de l'enfant sont un groupe hétérogène de pathologies rares et sévères pouvant survenir de la période néonatale jusqu'à l'âge adulte. Les étiologies sont multiples et incluent entre autres les anomalies des protéines du surfactant, ou l'hyperplasie des cellules neuroendocrines du nourrisson (NEHI). Le but de ce travail était de progresser dans la compréhension physiopathologique de deux PID liées au métabolisme du surfactant et de rechercher des pistes moléculaires dans les NEHI. La première partie a porté sur l'étude du variant V178M dans SFTPA1 et SFTPA2, identifié chez des patients atteints de PID et de cancers pulmonaires. Ces gènes codent pour la protéine du surfactant (SP)-A qui joue un rôle majeur dans l'homéostasie alvéolaire. Dans des cellules A549, des plasmides exprimant SP-A wild-type (WT) ou V178M ont été transfectés. L'étude par western blot a confirmé que l'expression protéique était conservée après transfection avec V178M. Dans un modèle de scratch mimant des lésions alvéolaires, une différence de réparation cellulaire après transfection avec V178M, et une mortalité plus importante ont été observées. L'étude par immunofluorescence avec l'anticorps anti PCNA (Proliferating Cell Nuclear Antigen) a montré une diminution de la prolifération cellulaire après transfection avec le variant. Nous avons montré que le taux d'IL-8 mesuré par ELISA était plus élevé dans le surnageant des cellules transfectées avec V178M par rapport au WT. Enfin, le traitement par dexaméthasone des cellules exprimant V178M entraînait une diminution du taux d'IL-8 et de la mortalité par rapport aux cellules non traitées. Cette étude confirme l'effet délétère du variant V178M de SP-A sur la prolifération et la mortalité cellulaires et a permis de mettre en évidence les mécanismes liés à un effet bénéfique de la corticothérapie. La deuxième partie du travail portait sur l'étude de 3 variants dans le gène NKX2.1 (Y214C, R165W et G147A) associés à des formes respiratoires létales de syndrome cerveau-poumon-thyroïde chez des nourrissons. Nous avons montré par western blot une expression protéique diminuée des deux variants R165W et Y214C, par rapport au WT et à G147A. La localisation nucléaire de la protéine NKX2.1 n'était pas affectée par les variants (immunofluorescence). Sur les pièces de biopsie pulmonaire de la patiente présentant le variant Y214C, l'expression de SP-C et de pro-SPC par rapport à un poumon témoin était absente. Enfin, les essais luciférase ont montré que le variant Y214C n'entraînait la transactivation d'aucun des promoteurs testés (SFTPB, SFTPC, thyroglobuline et thyroperoxydase), le variant R165W entraînait soit une augmentation soit une perte de de fonction des différents promoteurs. Le variant G147A se comportait comme le WT avec une transactivation similaire de tous les promoteurs testés. Ainsi, notre étude a permis d'affirmer et de préciser la pathogénicité des variants Y214C et R165W situés dans l'homéodomaine de NKX2.1 et, à ce stade, d'infirmer cette du variant G147A. La troisième partie du travail a porté sur l'étude génomique d'une cohorte de 20 patients atteints de NEHI. Il s'agissait d'une analyse de génomes entiers en trio des patients et de leurs deux parents. Nous avons d'abord identifié 4 gènes candidats (CMTR1, COL15A1, COLEC12, SRPK2) chez 4 patients différents parmi lesquels deux n'ont pas été retenus. En modifiant les filtres d'analyse, le gène SRRM2 a retenu notre attention puisqu'il a été identifié chez deux patients indépendants et qu'il est déjà connu pour être associé à un retard du neurodéveloppement. Au total, plusieurs éléments liés à la génétique des maladies respiratoires rares ont été étudiés. Des thérapeutiques ciblées pour les patients porteurs de variants SFTPA1 /SFTPA2, des corrélations phénotype-génotype pour les patients porteurs de variants NKX2.1, et de nouvelles pistes moléculaires dans les NEHI ont été envisagées.Interstitial Lung Diseases (ILD) in children are a heterogeneous group of rare and severe diseases that can occur from the neonatal period to adulthood. The aetiologies are numerous and include, among others, abnormalities in surfactant proteins or neuroendocrine cell hyperplasia of infancy (NEHI). This work aimed to advance the understanding of the pathophysiology of two surfactant-related ILDs and to explore molecular pathways in NEHI.The first part focused on the variant V178M in the SFTPA1 and SFTPA2 genes, identified in patients with ILD and lung cancers. These genes code for the surfactant protein (SP)-A, which plays a major role in alveolar homeostasis. In A549 cells, plasmids expressing either the wild-type (WT) SP-A protein or the variant V178M were transfected. Western blot analysis confirmed that protein expression was preserved after transfection with V178M. In a scratch model mimicking alveolar lesions, a difference in cell repair after transfection with V178M and increased mortality were observed. Immunofluorescence studies using the anti-PCNA (Proliferating Cell Nuclear Antigen) antibody showed a decrease in cell proliferation following transfection with the variant. We demonstrated that the level of IL-8 measured by ELISA was significantly higher in the supernatant of cells transfected with V178M compared to WT. Finally, treatment of cells with dexamethasone after transfection with V178M resulted in a significant reduction in IL-8 levels and mortality compared to untreated cells. This study confirms the deleterious effect of the SP-A variant V178M on cell proliferation and mortality and highlights mechanisms related to the beneficial effects of corticosteroid therapy.The second part of the work focused on the study of three variants in the NKX2.1 gene (Y214C, R165W, and G147A) associated with lethal respiratory phenotypes of brain-lung-thyroid syndrome in infants. We showed through western blot that the protein expression of the variants R165W and Y214C was significantly lower compared to WT and G147A. The nuclear localization of NKX2.1 protein was not affected by the variants (immunofluorescence). In lung biopsy specimens from the patient with the Y214C variant, there was a complete absence of expression of the surfactant protein SP-C and its precursor pro-SPC compared to a control. Finally, luciferase assays demonstrated that the Y214C variant did not activate any of the tested promoters (SFTPB, SFTPC, thyroglobulin, and thyroperoxydase), while the R165W variant either increased or decreased the function of the various promoters. The G147A variant behaved like the WT with similar transactivation of all tested promoters. Thus, our study allowed us to affirm and clarify the pathogenicity of the variants Y214C and R165W, located in the homeodomain of NKX2.1 and at this stage to rule out that of the G147A variant.The third part of the work involved the genomic study of a cohort of 20 patients with NEHI. This was a trio-based whole genome analysis of the patients and their two parents. We initially identified four candidate genes (CMTR1, COL15A1, COLEC12, SRPK2) in four independent patients, of which two were discarded. By modifying the analysis filters, the SRRM2 gene caught our attention as it was identified in two independent patients and is already known to be associated with neurodevelopmental disorders.Overall, several elements related to the genetics of rare respiratory diseases were studied. Targeted therapies for patients carrying SFTPA1/SFTPA2 variants, phenotype-genotype correlations for patients with NKX2.1 variants, and new molecular pathways in NEHI were considered
Observability analysis of power distribution systems with distributed energy resources using correlational measurements
No full textThesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2019Cataloged from PDF version of thesis.Includes bibliographical references (pages 57-59).In this thesis, an observability analysis framework is proposed for power distribution systems. The framework analyzes the sufficiency of the available measurements for monitoring the system. In the areas of the network where sufficient sensors have been deployed, the complex voltage at the nodes may be estimated. The framework also provides a metric that quantifies the accuracy of these voltage estimates. Due to the cost of sensors and the size of distribution systems, it is frequently the case that the available measurements are insufficient for complete observability of the system. In this thesis, the author proposes the use of Correlational Measurements (CMs) for improving distribution system observability by leveraging correlation between loads and between Distributed Energy Resources (DERs). Load correlation due to class-residential, commercial, industrial, etc.- is captured via correlational load measurements, the first type of CM. Injection correlation of DERs-such as wind turbines located in proximity-is captured via correlational DER measurements, the second type of CM. This thesis presents the CM formulation and derives modified node voltage and branch current based state estimators (NVSE and BCSE) accommodating CMs. Additionally, this thesis contains an on-line parameter estimation scheme for CMs that improves the accuracy of state estimates over time. The observability analysis framework with CMs is demonstrated through simulations on the IEEE 123 Node Distribution Test Feeder. It is shown that the introduction of CMs leads to improved observability of the system with only a 0.7% decrease in state estimation accuracy for NVSE and a 0.5% increase in state estimation accuracy for BCSE.by Yohan M. John.S.M.S.M. Massachusetts Institute of Technology, Department of Mechanical Engineerin
My ministry with primary children Central Presbyterian Church Atlanta, Georgia September 1970 - April 1972, 1973
No full text
IMP simulated mock community data set
No full text<p>This file contains the simulated mock (SM) metagenomic and metatranscriptomic dataset along with the original genomes used for simulation used within the article:</p>
<p><strong>IMP: a reproducible pipeline for reference-independent integrated metagenomic and metatranscriptomic analyses</strong></p>
<p>Shaman Narayanasamy<sup>†</sup>, Yohan Jarosz<sup>†</sup>, Emilie E.L. Muller, Cédric C. Laczny, Malte Herold, Anne Kaysen, Anna Heintz-Buschart, Nicolás Pinel, Patrick May, and Paul Wilmes<sup>*</sup></p>
<p>Preprint: http://biorxiv.org/content/early/2016/02/10/039263</p>
<p>The folder contains two subfolders (MG and MT), each containing the simulated metagenomic (MG) data and simulated metatranscriptomic (MT) data respectively. The files within these folders are in FASTQ format. The methods for generating these simulated data sets are described in the article.<br>
</p>
<p>The genomes and the resulting simulated metatranscriptomic data was generated and analysed within the article:</p>
<p><strong>Comparison of assembly algorithms for improving rate of metatranscriptomic functional annotation</strong></p>
<p>Albi Celaj, Janet Markle, Jayne Danska and John Parkinson; 2014; doi:10.1186/2049-2618-2-39</p>
<p> </p>
<p>It was provided upon request by the first author Albi Celaj, with permission to share the data. Please cite the aforementioned publication if this simulated metatranscriptomic data is used data is used.</p>
Efek Substitusi Akor Dan Tangga Nada Pentatonik Pada Mood Dalam Piano Jazz
No full textPenelitian ini berjudul "Efek Substitusi Akor Dan Tangga Nada Pentatonik Pada Mood Dalam Piano Jazz". Penelitian ini bertujuan untuk mengembangkan teknik improvisasi piano jazz dengan cara menggunakan substitusi akor dan tangga nada pentatonik sebagai bahan eksplorasi. Penggunaan substitusi akor sangat membantu dalam mengembangkan improvisasi sehingga dapat menambah nuansa baru. Penulis memilih lagu Are You Happy karya Yohan Kim untuk digunakan sebagai sarana eksplorasi yang representatif. Dalam menerapkan improvisasi tangga nada pentatonik, penulis menggunakan akor yang sudah disubstitusi sebagai acuan dan pondasi. Metode yang digunakan dalam penelitian ini adalah metode penelitian kualitatif dengan tahapan pengumpulan data yang terdiri dari observasi, studi dokumentasi, dan wawancara, kemudian analisis data yang didukung oleh metode eksplorasi dan penarikan kesimpulan. Dari proses penelitian dan penyajian yang sudah dilakukan, penulis menerapkan tangga nada pentatonik serta akor substitusi ke dalam improvisasi lagu Are You Happy karya Yohan Kim. Penulis berhasil menghadirkan ‘mood’ yang berbeda, unik dan baru dengan menerapkan improvisasi tangga nada pentatonik dan mensubstitusi akor improvisasi. Penerapan Tritone substitusi di akor ii dan V7 dalam improvisasi lagu tersebut bisa memberi pilihan tangga nada pentatonik dan bisa mengembangkan mood dalam berimprovisasi. Penerapan substitusi akor ke dalam improvisasi menggunakan tangga nada pentatonik dengan berbagai macam variasinya mampu menghasilkan mood yang berbeda.Kata kunci: Pentatonik, substitusi akor, improvisasi AbstractThis research is titled "The Effects of Chord Substitution and Pentatonic Scale on Mood in Jazz Piano." The aim of this study is to develop jazz piano improvisation techniques by using chord substitutions and the pentatonic scale as exploration materials. The use of chord substitution is highly beneficial in enhancing improvisation, adding new nuances to the music. The author chose the song "Are You Happy" by Yohan Kim as a representative tool for exploration. When applying pentatonic scale improvisation, the author used substituted chords as references and foundations.The research methodology employed in this study is qualitative research, involving data collection stages such as observation, documentary study, and interviews. Data analysis is supported by exploration methods and drawing conclusions. Through the research process and presentation, the author applied the pentatonic scale and chord substitutions to the improvisation of the song "Are You Happy" by Yohan Kim. The author successfully introduced a different, unique, and new mood by applying pentatonic scale improvisation and chord substitutions. The implementation of Tritone substitution in the ii and V7 chords in the improvisation of the song provides options for pentatonic scales and contributes to mood development in improvisation. The application of chord substitution in improvisation using the pentatonic scale, with its various variations, can generate different moodsKeywords: pentatonic, subtitution acord, improvisatio
Ultrafast fluxional exchange dynamics in electrolyte solvation sheath of lithium ion battery
No full textLithium cation is the charge carrier in lithium-ion battery. Electrolyte solution in lithium-ion battery is usually based on mixed solvents consisting of polar carbonates with different aliphatic chains. Despite various experimental evidences indicating that lithium ion forms a rigid and stable solvation sheath through electrostatic interactions with polar carbonates, both the lithium solvation structure and more importantly fluctuation dynamics and functional role of carbonate solvent molecules have not been fully elucidated yet with femtosecond vibrational spectroscopic methods. Here we investigate the ultrafast carbonate solvent exchange dynamics around lithium ions in electrolyte solutions with coherent two-dimensional infrared spectroscopy and find that the time constants of the formation and dissociation of lithium-ion center dot center dot center dot carbonate complex in solvation sheaths are on a picosecond timescale. We anticipate that such ultrafast microscopic fluxional processes in lithium-solvent complexes could provide an important clue to understanding macroscopic mobility of lithium cation in lithium-ion battery on a molecular level
ⓒ The Author(s) 2017112111sciescopu
Climate finance in the Asia-Pacific : trends and innovative approaches
No full textThis discussion paper 'Climate finance in the Asia-Pacific: Trends and Innovative Approaches' was prepared for ESCAP by Ilaria Carrozza, PhD Candidate, Department of International Relations, London School of Economics and Political Science, London, UK
The author would like to acknowledge ESCAP Environment and Development Division (Rae Kwon Chung, Aneta Nikolova, Riccardo Mesiano, Hala Razian, and with support from Yohan Hong). A peer review was conducted by Climate Policy Initiative (Mia Fitri and Leela Raina)
Analysis of Loading Policies for Multi-model Inference on the Edge
No full textThe increasingly growing expansion of the Internet of Things (IoT) along with the convergence of multiple technologies such as the arrival of next generation wireless broadband in 5G, is creating a paradigm shift from cloud computing towards edge computing. Performing tasks normally done by the cloud directly on edge devices would ensure multiple benefits such as latency gains and a more robust privacy of data. However, edge devices are resource-constrained and often do not possess the computational and memory capabilities to perform demanding tasks. Complex algorithms such as the training and inference of a complete Deep Neural Network (DNN) is often not feasible on these devices.In this paper we perform a novel empirical study of the various ways that multiple inference tasks of deep learning models can be loaded on these edge devices. We analyse the run time gain, under different resource limits, of various DNN layer loading policies that aim to optimize the overall run time of consecutive inference tasks. We combine this with further research in the memory usage and swapping behaviour when performing these inference tasks. Using these results, we show that if the memory overhead becomes too large, loading and executing DNN layers in an interleaved manner provides significant gains in run time. This is achieved trough multiple experiments in our specially made evaluation environment EdgeCaffe which is presented in this paper as well.Optimizing Multiple Deep Learning Models on Edge DevicesCSE3000 Research ProjectComputer Science and Engineerin
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