52 research outputs found

    Sähköurakan laskeminen uudiskohteeseen määrälaskentaohjelmaa hyödyntäen

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    Tässä opinnäytetyössä selvitetään, mitä hyötyjä ohjelmallisella tarjouslaskennalla on verrattuna perinteiseen käsin tehtävään tarjouslaskentaan. Työssä vertaillaan käsintehdyn sekä ohjelmallisen laskennan eroavaisuuksia uudiskohteessa, joka on kolmen rivitalon kokonaisuus ja suunniteltu vanhusten käyttöön. Opinnäytetyö tehtiin yhteistyössä Sähkö-Säe Oy:n kanssa. Ohjelmallinen urakkalaskenta suoritettiin työssä JCAD sähkömäärät määrälaskentaohjelmalla. JCAD:sta saadut laskennan tulokset tuotiin Pajadatan Xpaja-ohjelman tarjouslaskentaosioon. Tämän jälkeen saatiin JCAD:n tuottamien tarvikelistojen avulla tuotteet, joita kohteeseen laskettiin ja ohjelman laskeman ajan työlle. Tämän jälkeen saatiin laskettua euromääräinen hinta urakalle määräluetteloiden sekä työhön kuuluvan ajan perusteella. Urakkalaskenta ohjelmalla saatuja tuloksia vertaillaan työssä käsin tehtyyn laskentaan ja selvitetään, mistä eroavaisuudet hinnassa syntyvät. Työssä nähdään laskennalliset erot tarvikkeiden sekä työhön käytetyn ajan perusteella. Lopuksi käydään ohjelmallisen laskennan edut käsin tehtyyn laskentaan ja millä tavoin JCAD määrälaskentaohjelmisto auttaisi yritystä tarjouslaskentaa tehdessä.The purpose of this thesis was to determine the benefits of using programmable calculations instead of the traditional manual calculations. The thesis was done by comparing manual calculations and programmable computations in a new construction, a three terraced house complex designed for the elderly. This thesis was made in cooperation with the Sähkö-Säe Oy. Programmable calculation was made with JCAD electicity quantity program. Results of the JCAD were transferred to Pajadata Xpaja program. The Xpaja program results were put into a list of articles and times of calculated working hours. After this, calculated contract price was obtained with the list of the articles and working time. The results were computational difference in articles and work time. Finally comparing manual calculations and programmable calculations, JCAD electricity quantity program will be a good option to help the company with calculation

    Common colonic community indicators of the suckling pig microbiota where diversity and abundance correlate with performance

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    The primary objective of this study was to investigate if common colonic community indicators could be identified from the microbiota of 22-day-old suckling pigs in repeated small-scale trials. A total of three separate trials were conducted at different times in the same year and facility with genetically similar animals. Colonic samples were collected from four pigs in each trial and the microbiome composition assessed by 16s rRNA gene sequencing. Pig weight, average daily gain (ADG), bacterial diversity, and abundance were not significantly different between repeated trials, except for a significant difference in Jaccard Similarity. At genus level, the most abundant taxa identified were Porphyromonadaceae unclassified (15.81%), Ruminococcaceae unclassified, (12.78%), Prevotella (7.26%), Clostridiales unclassified (6.99%), Lactobacillus (6.58%), Phascolarctobacterium (6.52%), and Firmicutes unclassified (5.69%). The secondary objective was to establish if pooled data in terms of microbial diversity and abundance of the colonic microbiota related to weight and ADG. Pig weight at day 22 and ADG positively correlated with α-diversity. Abundance of potential protein digesting and short-chain fatty acid producing operational taxonomic units ascribed to Terrisporobacter, Ruminococcaceae unclassified, Intestinimonas, and Dorea correlated with weight and ADG, suggesting a nutritional role for these common colonic community microbiota members in suckling pigs

    Viabilité et quantification d’une levure probiotique dans le système digestif du porc

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    Viability and colonisation of a probiotic yeast in the digestive tract of pigletsProbiotics have been defined as « live microorganisms which when administered in adequate amounts confer a health benefit on the host» (WHO, 2001). This definition implies that viability is an important factor and that the probiotic needs to reach its target site alive and in significant number in order to confer beneficial properties. Therefore, we investigated the survival and the level of the probiotic yeast Saccharomyces cerevisiae CNCM I-1079 (SB) along the gut of pigs and in faeces. For this purpose, 3 piglets from SB supplemented sows were orally dosed with SB for a week before sacrifice at 21 days of age. Faecal samples were collected as well as intestinal tract compartment content for yeast count and characterization. We have used advanced techniques to be able to identify and enumerate accurately SB from other yeasts according to morphology and biomolecular profile criteria. We have demonstrated that SB remains viable and in proportionally high number along the gut of pigs and in faeces, suggesting that both sites of main actions for probiotics (small intestine and hindgut) can benefit from the presence of live yeast cells at a biologically significant level

    Group 2 innate lymphoid cells and reproduction

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    Regulation of the immune system and of uterine tissue homeostasis, growth, and remodelling are deeply intertwined during pregnancy and are essential for successful reproduction. Recent findings showed that tissue-resident innate lymphoid cells (ILCs) are crucial regulators of both physiology and pathology of the tissues they populate. Uterine natural killer (uNK) cells are a subtype of ILCs known to regulate trophoblast invasion, uterine vascular adaptation to pregnancy, and foetal growth. We recently described additional types of ILCs in the uterus of women and mice. However, the role of these ILCs during reproduction is unknown. Among them, group 2 ILCs (ILC2s) have been previously characterised in other tissues, in which they modulate immune cells and tissue homeostasis by producing type-2 cytokines and growth factors (i.e. IL-4, IL-5, IL-13, and Amphiregulin). Based on these premises, I hypothesized that uterine ILC2s (uILC2s) regulate uterine immune homeostasis and thus contribute to successful reproduction. To test this, I first characterised the uILC subtypes present in humans and mice at various stages of the reproductive cycle. Secondly, I addressed the functional role of uILC2s during pregnancy by taking advantage of a uILC2 knockout mouse model. My results show that uterine ILC2s represent <1% and <0.1% of murine and human uterine leukocytes, respectively. However, as they can quickly produce large amounts of cytokines, uILCs are capable of potently affect both other immune cells and the surrounding tissue. Indeed, I found that compared to other tissue-resident ILC2s, uILC2s produce high levels of IL-5 and Areg even in the absence of any stimulation. On the contrary, non-uterine ILC2s mainly produce IL-13, which is lowly expressed by uILC2s. To further characterize the tissuespecific properties of uILC2s, I then performed RNAseq on uILC2s isolated from virgin, midgestation, and term murine uterus, and I compared their transcriptomes with those of ILC2s from lung, intestine, and bone marrow. Interestingly, uILC2s specifically express granzymes and genes typical of regulatory T cells. Therefore, uILC2s have tissue-specific properties and are modulated during pregnancy. Furthermore, the ability of uILC2s to produce IL-5 and Areg suggests that they may be crucial in the regulation of uterine type-2 immunity. I then studied the phenotype of Roraflox/floxIl7racre/wtRora^{flox/flox}Il7ra^{cre/wt}(ILC2KO) mouse models, as well as that of mice lacking the ILC2 activating cytokine IL-33 (IL33cit/citIL33^{cit/cit}; IL33KO). I examined the immune microenvironment in both the myometrium and decidua in ILC2KO mice and found alterations in type-2 cytokines and myeloid cell homeostasis. In particular, in absence of ILC2s, IL-4 and IL-5 are dramatically reduced, IL-13 is absent, and decidual inflammatory cytokines IL1β and IL-6 are increased. Furthermore, uterine dendritic cells (uDC), uterine macrophages (uMac), and uterine neutrophils (uN) increase, while uterine eosinophils (uEo) are virtually absent. These results show that uILC2s regulate uterine type-2 immunity, suggesting that uILC2s could be important during pregnancy. Accordingly, I found that lack of uILC2s leads to insufficient spiral artery remodelling and restricted foetal growth. Type-2 cytokines and in particular IL-4 regulates alternative activation of Macrophages (Mac) and Dendritic Cells (DCs), which promote the development of an anti-inflammatory environment and facilitate tissue remodelling. I hypothesised that similar mechanisms occur in the uterus and that uILC2s have a central role in the polarisation of the immune response. To explore this, I studied in more detail the characteristics of uEo, uMac, and uDCs dissected from wild type and ILC2KO mice. I found a reduction in genes associated with alternative activation in uMac and uDCs in the uterus of pregnant ILC2KO mice. Additionally, I showed that uEo are the main producers of the IL-4. This demonstrates that uILC2s promote alternative activation of myeloid cell population by modulating the uterine immune microenvironment. I then assessed the role of uILC2s-dependent type-2 immunity in inflammatory pathology following a type-1 response to bacterial infection. When challenged with LPS, pregnant ILC2KO mice showed more pronounced foetal demise. Therefore, uILC2s regulate uterine type-2 immune homeostasis and this prevents inflammatory pathology. Collectively, my work advances our knowledge of the innate immune mechanisms that control physiological and pathological events during pregnancy. These findings have implications to the field of immunology of pregnancy and may lead to clinical progress in diagnosis and prevention of infection-induced abortion in human pregnancies.Centre for trophoblast research (CTR

    Synthesis and biological activity of a cytostatic inhibitor of MLLr leukemia targeting the DOT1L protein

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    Histone methyltransferase DOT1L catalyzes mono-, di-and trimethylation of histone 3 at lysine residue 79 (H3K79) and hypermethylation of H3K79 has been linked to the development of acute leukemias characterized by the MLL (mixed-lineage leukemia) rearrangements (MLLr cells). The inhibition of H3K79 methylation inhibits MLLr cells proliferation, and an inhibitor specific for DOT1L, pinometostat, was in clinical trials (Phase Ib/II). However, the compound showed poor pharmacological properties. Thus, there is a need to find new potent inhibitors of DOT1L for the treatment of rearranged leukemias. Here we present the design, synthesis, and biological evaluation of a small molecule that inhibits in the nM level the enzymatic activity of hDOT1L, H3K79 methylation in MLLr cells with comparable potency to pinometostat, associated with improved metabolic stability and a characteristic cytostatic effect

    Construction of a questionnaire on the suicidal beliefs : « ASP suicide »

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