Comprehensive Forced Response Analysis of J2X Turbine Bladed-Discs with 36- Degree Variation in CFD Loading

At NASA/MSFC, Structural Dynamics personnel continue to perform advanced analysis for the turbomachinery in the J2X Rocket Engine, which is under consideration for the new Space Launch System. One of the most challenging analyses in the program is predicting turbine blade structural capability. Resonance was predicted by modal analysis, so comprehensive forced response analyses using high fidelity cyclic symmetric finite element models were initiated as required. Analysis methodologies up to this point have assumed the flow field could be fully described by a sector, so the loading on every blade would be identical as it travelled through it. However, in the J2X the CFD flow field varied over the 360 deg of a revolution because of the flow speeds and tortuous axial path. MSFC therefore developed a complex procedure using Nastran Dmap's and Matlab scripts to apply this circumferentially varying loading onto the cyclically symmetric structural models to produce accurate dynamic stresses for every blade on the disk. This procedure is coupled with static, spin, and thermal loading to produce high cycle fatigue safety factors resulting in much more accurate analytical assessments of the blades

Drosophila melanogaster as a Model Host for the Burkholderia cepacia Complex

Colonization with bacterial species from the Burkholderia cepacia complex (Bcc) is associated with fast health decline among individuals with cystic fibrosis. In order to investigate the virulence of the Bcc, several alternative infection models have been developed. To this end, the fruit fly is increasingly used as surrogate host, and its validity to enhance our understanding of host-pathogen relationships has been demonstrated with a variety of microorganisms. Moreover, its relevance as a suitable alternative to mammalian hosts has been confirmed with vertebrate organisms.The aim of this study was to establish Drosophila melanogaster as a surrogate host for species from the Bcc. While the feeding method proved unsuccessful at killing the flies, the pricking technique did generate mortality within the populations. Results obtained with the fruit fly model are comparable with results obtained using mammalian infection models. Furthermore, validity of the Drosophila infection model was confirmed with B. cenocepacia K56-2 mutants known to be less virulent in murine hosts or in other alternative models. Competitive index (CI) analyses were also performed using the fruit fly as host. Results of CI experiments agree with those obtained with mammalian models.We conclude that Drosophila is a useful alternative infection model for Bcc and that fly pricking assays and competition indices are two complementary methods for virulence testing. Moreover, CI results indicate that this method is more sensitive than mortality tests

The Imd Pathway Is Involved in Antiviral Immune Responses in Drosophila

Cricket Paralysis virus (CrPV) is a member of the Dicistroviridae family of RNA viruses, which infect a broad range of insect hosts, including the fruit fly Drosophila melanogaster. Drosophila has emerged as an effective system for studying innate immunity because of its powerful genetic techniques and the high degree of gene and pathway conservation. Intra-abdominal injection of CrPV into adult flies causes a lethal infection that provides a robust assay for the identification of mutants with altered sensitivity to viral infection. To gain insight into the interactions between viruses and the innate immune system, we injected wild type flies with CrPV and observed that antimicrobial peptides (AMPs) were not induced and hemocytes were depleted in the course of infection. To investigate the contribution of conserved immune signaling pathways to antiviral innate immune responses, CrPV was injected into isogenic mutants of the Immune Deficiency (Imd) pathway, which resembles the mammalian Tumor Necrosis Factor Receptor (TNFR) pathway. Loss-of-function mutations in several Imd pathway genes displayed increased sensitivity to CrPV infection and higher CrPV loads. Our data show that antiviral innate immune responses in flies infected with CrPV depend upon hemocytes and signaling through the Imd pathway

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Sine oculis homeobox homolog 1 plays a critical role in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with limited treatment options. The role of the developmental transcription factor Sine oculis homeobox homolog 1 (SIX1) in the pathophysiology of lung fibrosis is not known. IPF lung tissue samples and IPF-derived alveolar type II cells (AT2) showed a significant increase in SIX1 mRNA and protein levels, and the SIX1 transcriptional coactivators EYA1 and EYA2 were elevated. Six1 was also upregulated in bleomycin-treated (BLM-treated) mice and in a model of spontaneous lung fibrosis driven by deletion of Telomeric Repeat Binding Factor 1 (Trf1) in AT2 cells. Conditional deletion of Six1 in AT2 cells prevented or halted BLM-induced lung fibrosis, as measured by a significant reduction in histological burden of fibrosis, reduced fibrotic mediator expression, and improved lung function. These effects were associated with increased macrophage migration inhibitory factor (MIF) in lung epithelial cells in vivo following SIX1 overexpression in BLM-induced fibrosis. A MIF promoter-driven luciferase assay demonstrated direct binding of Six1 to the 5-TCAGG-3 consensus sequence of the MIF promoter, identifying a likely mechanism of SIX1-driven MIF expression in the pathogenesis of lung fibrosis and providing a potentially novel pathway for targeting in IPF therapy

Laatujohtaminen valmistavassa teollisuudessa : Toimintajärjestelmän uudistaminen

Opinnäytetyön toimeksiantajana oli Savonlinnassa toimiva lujitemuovituotteisiin erikoistunut valmistusyritys Oy Esmarin Composites Ltd. Yrityksellä on ollut SFS-EN ISO 9001:2008 -mukainen sertifiointi vuodesta 2012. Yrityksen laatujärjestelmä kattaa kaikki yrityksen toiminnot, ja ne on dokumentoitu toimintakäsikirjaan. Opinnäytetyön tavoitteena oli perehtyä laatujohtamiseen valmistavassa teollisuudessa ja uudistaa yrityksen toimintajärjestelmää. Yrityksen selainpohjaisella alustalla oleva toimintakäsikirja liitteineen siirrettiin uudelle alustalle. Toimenpiteen tavoitteena oli toimintakäsikirjan käytön selkeyttäminen ja maksullisesta selainpohjaisesta dokumentoinnista eroon pääseminen. Toimintakäsikirjan ja sen liitteiden uusiksi alustoiksi valikoituivat Microsoft Office –ohjelmistot yleisyytensä vuoksi. Toimintakäsikirjan tekstidokumentaatioiden ulkoasu päivitettiin ja tarvittavia tiedonkeruulomakkeita tehtiin Microsoft Wordin ja Excelin avulla; muun muassa poikkeamista johtuvien kustannusten seurantaan asiakaskohtaisesti tehtiin Excelillä toimiva tiedonkeruumenetelmä. Opinnäytetyön teon aloitusajankohdan vuoksi opinnäytetyössä ei ole vielä otettu huomioon SFS-EN ISO 9001:2015:n päivityksiä. Yrityksen on nyt kuitenkin selkeämmän dokumentaation avulla helpompi päivittää johtamisjärjestelmäänsä uusien vaatimuksien mukaiseksi.This thesis was commissioned by Oy Esmarin Composites Ltd. The company specializes in the manufacture of reinforced plastic products and the company has had ISO 9001:2008 standardization since 2012. The company’s quality management system covers all the company’s operations and they are documented in the operations manual. Aim of this thesis was familiarize to quality management in the manufacturing industry and transfer the company’s web-based platform operating manual with attachments to a new platform. The purpose was to clarify the use of the operations manual and replace the browser-based documentation. Microsoft Office software was selected to new platform for the operations manual and its attachments, because they are public software. The layout of the operations manual was updated and the necessary data collection forms were made in Microsoft Word and Excel, for example a separate Excel program was made to calculate the cost of deviations. Because this thesis was started in the beginning of the year 2015 update from ISO 9001:2008 standard to ISO 9001:2015 has not yet been taken into consideration. The company’s operations manual is now clearer and easy to use so updating the management system according to the requirements is easier