Sensor and Actuator Needs for More Intelligent Gas Turbine Engines

This paper provides an overview of the controls and diagnostics technologies, that are seen as critical for more intelligent gas turbine engines (GTE), with an emphasis on the sensor and actuator technologies that need to be developed for the controls and diagnostics implementation. The objective of the paper is to help the "Customers" of advanced technologies, defense acquisition and aerospace research agencies, understand the state-of-the-art of intelligent GTE technologies, and help the "Researchers" and "Technology Developers" for GTE sensors and actuators identify what technologies need to be developed to enable the "Intelligent GTE" concepts and focus their research efforts on closing the technology gap. To keep the effort manageable, the focus of the paper is on "On-Board Intelligence" to enable safe and efficient operation of the engine over its life time, with an emphasis on gas path performanc

Signatures of human regulatory T cells: an encounter with old friends and new players

BACKGROUND: Naturally occurring CD4(+)CD25(+ )regulatory T cells (T(Reg)) are involved in the control of autoimmune diseases, transplantation tolerance, and anti-tumor immunity. Thus far, genomic studies on T(Reg )cells were restricted to murine systems, and requirements for their development, maintenance, and mode of action in humans are poorly defined. RESULTS: To improve characterization of human T(Reg )cells, we compiled a unique microarray consisting of 350 T(Reg )cell associated genes (Human T(Reg )Chip) based on whole genome transcription data from human and mouse T(Reg )cells. T(Reg )cell specific gene signatures were created from 11 individual healthy donors. Statistical analysis identified 62 genes differentially expressed in T(Reg )cells, emphasizing some cross-species differences between mice and humans. Among them, several 'old friends' (including FOXP3, CTLA4, and CCR7) that are known to be involved in T(Reg )cell function were recovered. Strikingly, the vast majority of genes identified had not previously been associated with human T(Reg )cells (including LGALS3, TIAF1, and TRAF1). Most of these 'new players' however, have been described in the pathogenesis of autoimmunity. Real-time RT-PCR of selected genes validated our microarray results. Pathway analysis was applied to extract signaling modules underlying human T(Reg )cell function. CONCLUSION: The comprehensive set of genes reported here provides a defined starting point to unravel the unique characteristics of human T(Reg )cells. The Human T(Reg )Chip constructed and validated here is available to the scientific community and is a useful tool with which to study the molecular mechanisms that orchestrate T(Reg )cells under physiologic and diseased conditions

E-procurement in Public Organization

Tampereen kaupungin kokonaishankinnoista vain kaksi prosenttia tehtiin toiminnanohjausjärjestelmällä vuonna 2013. Järjestelmän matalasta käyttöasteesta johtuen hankintatiedot puuttuvat järjestelmästä, mikä hankaloittaa hankintojen strategista johtamista. Työn taustalla on tarve tehostaa toimintoja ja saada aikaan kustannussäästöjä sekä saada hankinnoista enemmän tietoa niiden tehokkaammaksi johtamiseksi. Tutkimuksen tarkoituksena oli tunnistaa keinoja, joiden avulla Tampereen kaupungin ostamista voidaan kehittää sähköisellä ostojärjestelmällä. Päätavoitteena oli kaupungin ostamisen nykytilan selvittäminen ja siihen soveltuvan sähköisen ratkaisun vaatimusten määrittely. Tässä työssä keskityttiin työn toimeksiantajan Tampereen Logistiikan valitsemien Tampereen kaupungin yksiköiden Infran, Kotihoidon ja Tilakeskuksen ostamisen kehittämiseen. Tutkimus toteutettiin laadullisena monimenetelmäisenä tapaustutkimuksena. Aineistona käytettiin kirjallisuutta, vanhoja Tampereen kaupungin selvityksiä sekä kohdeyksiköiden ja muiden kaupunkien hankinnoista vastaavien henkilöiden haastatteluja. Aikaisempi kirjallisuus on käsitellyt ostamisen suhdetta hankintoihin ja toimitusketjuun sekä tarkastellut sähköistä ostamista keinona tehostaa hankintoja. Tutkimuksen empiriaosuus esittelee ensin havaintoja aikaisemmista tutkimuksista sekä muiden kaupunkien benchmark-analyysistä. Toisessa osassa käsitellään ostotoimintaa ja sen kehitysmahdollisuuksia kohdeorganisaation valikoiduissa yksiköissä. Aineistoanalyysin tuloksena tunnistettiin ostamisen ongelmaksi kirjavat ostoprosessit sekä niistä aiheutuvat prosessikustannukset. Tuloksina saatiin ostamisen asettamia vaatimuksia ostojärjestelmälle, joita ovat noutojen kirjaus ja mobiilikäyttömahdollisuus. Ratkaisuehdotuksena annettiin malli uudesta prosessista, johon sitoutuu vähemmän työaikaa aikaisempaan verrattuna sekä ehdotettiin katalogien käyttöönottamista kaupungin omassa järjestelmässä

Next-generation insights into regulatory T cells: expression profiling and FoxP3 occupancy in Human

Regulatory T-cells (Treg) play an essential role in the negative regulation of immune answers by developing an attenuated cytokine response that allows suppressing proliferation and effector function of T-cells (CD4+ Th). The transcription factor FoxP3 is responsible for the regulation of many genes involved in the Treg gene signature. Its ablation leads to severe immune deficiencies in human and mice. Recent developments in sequencing technologies have revolutionized the possibilities to gain insights into transcription factor binding by ChiP-seq and into transcriptome analysis by mRNA-seq. We combine FoxP3 ChiP-seq and mRNA-seq in order to understand the transcriptional differences between primary human CD4+ T helper and regulatory T-cells, as well as to study the role of FoxP3 in generating those differences. We show, that mRNA-seq allows analyzing the transcriptomal landscape of T-cells including the expression of specific splice variants at much greater depth than previous approaches, whereas 50% of transcriptional regulation events have not been described before by using diverse array technologies. We discovered splicing patterns like the expression of a kinase-dead isoform of IRAK1 upon T-cell activation. The immunoproteasome is up-regulated in both Treg and CD4+ Th cells upon activation, whereas the ‘standard’ proteasome is up-regulated in Tregs only upon activation

Next-generation insights into regulatory T cells: expression profiling and FoxP3 occupancy in Human

Regulatory T-cells (Treg) play an essential role in the negative regulation of immune answers by developing an attenuated cytokine response that allows suppressing proliferation and effector function of T-cells (CD4+ Th). The transcription factor FoxP3 is responsible for the regulation of many genes involved in the Treg gene signature. Its ablation leads to severe immune deficiencies in human and mice. Recent developments in sequencing technologies have revolutionized the possibilities to gain insights into transcription factor binding by ChiP-seq and into transcriptome analysis by mRNA-seq. We combine FoxP3 ChiP-seq and mRNA-seq in order to understand the transcriptional differences between primary human CD4+ T helper and regulatory T-cells, as well as to study the role of FoxP3 in generating those differences. We show, that mRNA-seq allows analyzing the transcriptomal landscape of T-cells including the expression of specific splice variants at much greater depth than previous approaches, whereas 50% of transcriptional regulation events have not been described before by using diverse array technologies. We discovered splicing patterns like the expression of a kinase-dead isoform of IRAK1 upon T-cell activation. The immunoproteasome is up-regulated in both Treg and CD4+ Th cells upon activation, whereas the ‘standard’ proteasome is up-regulated in Tregs only upon activation

Genotype-Dependent Tumor Regression in Marek’s Disease Mediated at the Level of Tumor Immunity

Marek’s disease (MD) of chickens is a unique natural model of Hodgkin’s and Non Hodgkin’s lymphomas in which the neoplastically-transformed cells over-express CD30 (CD30hi) antigen. All chicken genotypes can be infected with MD virus and develop microscopic lymphomas. From 21 days post infection (dpi) microscopic lymphomas regress in resistant chickens but, in contrast, they progress to gross lymphomas in susceptible chickens. Here we test our hypothesis that in resistant chickens at 21 dpi the tissue microenvironment is pro T-helper (Th)-1 and compatible with cytotoxic T lymphocyte (CTL) immunity but in susceptible lines it is pro Th-2 or pro T-regulatory (T-reg) and antagonistic to CTL immunity. We used the B2, non-MHC-associated, MD resistance/susceptibility system (line [L]61/line [L]72) and quantified the levels of key mRNAs that can be used to define Th-1 (IL-2, IL-12, IL-18, IFNγ), Th-2 (IL-4, IL-10) and T-reg (TGFβ, GPR-83, CTLA-4, SMAD-7) lymphocyte phenotypes. We measured gene expression in both whole tissues (represents tissue microenvironment and tumor microenvironment) and in the lymphoma lesions (tumor microenvironment) themselves. Gene ontology-based modeling of our results shows that the dominant phenotype in whole tissue as well as in microscopic lymphoma lesions, is pro T-reg in both L61 and L72 but a minor pro Th-1 and anti Th-2 tissue microenvironment exists in L61 whereas there is an anti Th-1 and pro Th-2 tissue microenvironment in L72. The tumor microenvironment per se is pro T-reg, anti Th-1 and pro Th-2 in both L61 and L72. Together our data suggests that the neoplastic transformation is essentially the same in both L61 and L72 and that resistance/susceptibility is mediated at the level of tumor immunity in the tissues

Nutritional, Health, and Technological Functionality of Lupin Flour Addition to Bread and Other Baked Products: Benefits and Challenges

Lupin is an undervalued legume despite its high protein and dietary fiber content and potential health benefits. This review focuses on the nutritional value, health benefits, and technological effects of incorporating lupin flour into wheat-based bread. Results of clinical studies suggest that consuming lupin compared to wheat bread and other baked products reduce chronic disease risk markers; possibly due to increased protein and dietary fiber and bioactive compounds. However, lupin protein allergy has also been recorded. Bread quality has been improved when 10% lupin flour is substituted for refined wheat flour; possibly due to lupin-wheat protein cross-linking assisting bread volume and the high water-binding capacity (WBC) of lupin fiber delaying staling. Above 10% substitution appears to reduce bread quality due to lupin proteins low elasticity and the high WBC of its dietary fiber interrupting gluten network development. Gaps in understanding of the role of lupin flour in bread quality include the optimal formulation and processing conditions to maximize lupin incorporation, role of protein cross-linking, antistaling functionality, and bioactivity of its γ-conglutin protein

Implementation of exon arrays: alternative splicing during T-cell proliferation as determined by whole genome analysis

<p>Abstract</p> <p>Background</p> <p>The contribution of alternative splicing and isoform expression to cellular response is emerging as an area of considerable interest, and the newly developed exon arrays allow for systematic study of these processes. We use this pilot study to report on the feasibility of exon array implementation looking to replace the 3' <it>in vitro </it>transcription expression arrays in our laboratory.</p> <p>One of the most widely studied models of cellular response is T-cell activation from exogenous stimulation. Microarray studies have contributed to our understanding of key pathways activated during T-cell stimulation. We use this system to examine whole genome transcription and alternate exon usage events that are regulated during lymphocyte proliferation in an attempt to evaluate the exon arrays.</p> <p>Results</p> <p>Peripheral blood mononuclear cells form healthy donors were activated using phytohemagglutinin, IL2 and ionomycin and harvested at 5 points over a 7 day period. Flow cytometry measured cell cycle events and the Affymetrix exon array platform was used to identify the gene expression and alternate exon usage changes. Gene expression changes were noted in a total of 2105 transcripts, and alternate exon usage identified in 472 transcript clusters. There was an overlap of 263 transcripts which showed both differential expression and alternate exon usage over time. Gene ontology enrichment analysis showed a broader range of biological changes in biological processes for the differentially expressed genes, which include cell cycle, cell division, cell proliferation, chromosome segregation, cell death, component organization and biogenesis and metabolic process ontologies. The alternate exon usage ontological enrichments are in metabolism and component organization and biogenesis. We focus on alternate exon usage changes in the transcripts of the spliceosome complex. The real-time PCR validation rates were 86% for transcript expression and 71% for alternate exon usage.</p> <p>Conclusions</p> <p>This study illustrates that the Exon array technology has the potential to provide information on both transcript expression and isoform usage, with very little increase in expense.</p

TGF-β induces TIAF1 self-aggregation via type II receptor-independent signaling that leads to generation of amyloid β plaques in Alzheimer's disease

The role of a small transforming growth factor beta (TGF-β)-induced TIAF1 (TGF-β1-induced antiapoptotic factor) in the pathogenesis of Alzheimer's disease (AD) was investigated. TIAF1 physically interacts with mothers against DPP homolog 4 (Smad4), and blocks SMAD-dependent promoter activation when overexpressed. Accordingly, knockdown of TIAF1 by small interfering RNA resulted in spontaneous accumulation of Smad proteins in the nucleus and activation of the promoter governed by the SMAD complex. TGF-β1 and environmental stress (e.g., alterations in pericellular environment) may induce TIAF1 self-aggregation in a type II TGF-β receptor-independent manner in cells, and Smad4 interrupts the aggregation. Aggregated TIAF1 induces apoptosis in a caspase-dependent manner. By filter retardation assay, TIAF1 aggregates were found in the hippocampi of nondemented humans and AD patients. Total TIAF1-positive samples containing amyloid β (Aβ) aggregates are 17 and 48%, respectively, in the nondemented and AD groups, suggesting that TIAF1 aggregation occurs preceding formation of Aβ. To test this hypothesis, in vitro analysis showed that TGF-β-regulated TIAF1 aggregation leads to dephosphorylation of amyloid precursor protein (APP) at Thr668, followed by degradation and generation of APP intracellular domain (AICD), Aβ and amyloid fibrils. Polymerized TIAF1 physically interacts with amyloid fibrils, which would favorably support plaque formation in vivo