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SCARFÒ, REBECCA. "Precise characterization of hemogenic endothelial cells during human hematopoietic development." Doctoral thesis, Università Vita-Salute San Raffaele, 2022. http://hdl.handle.net/20.500.11768/128259.
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During embryonic development, blood cells emerge from a subset of specialized endothelial cells, named hemogenic endothelium (HE), via a process known as endothelial-to-hematopoietic transition (EHT). HE represents a heterogeneous population found in various anatomical sites, including the yolk sac (YS) and the aorta-gonad-mesonephros (AGM). It comprises cells that differ in developmental potential, thus defining distinct hematopoietic programs. Despite the endothelial descendancy of blood cells is well established, the identity of HE is still debated. A more thorough characterization of HE is therefore essential to guide the efforts to derive this population from human pluripotent stem cells (hPSCs), a critical step to generate therapeutic blood products in vitro. However, current known markers used to isolate HE are insufficient as they also enrich associated arterial cells. To identify specific human HE markers, we performed transcriptomic analysis of 4-5-week-old human embryos, a developmental stage characterized by active EHT. We identified FCGR2B encoding for the Fc receptor CD32, previously associated with other specialized endothelia, as enriched gene in the ACE+CD34+ population that contains HE. Functional ex vivo analyses confirmed that multilineage hematopoietic potential is highly enriched in CD32+ endothelial cells isolated from the AGM and YS of human embryos. In addition, CD32 emerged as selective marker for hPSC-derived HE across different hematopoietic programs. Remarkably, our analyses showed that CD32 specificity for cells with hemogenic potential is superior to other known HE markers in hPSC-derived hematopoietic cultures. These findings provide a simple method for isolating HE from human embryos and hPSCs, allowing its molecular characterization as well as the efficient generation of hematopoietic cells in vitro.Durante lo sviluppo embrionale, le cellule del sangue emergono da un sottoinsieme di cellule endoteliali specializzate, denominate endotelio emogeno (HE), attraverso un processo noto come transizione endoteliale-ematopoietica (EHT). HE è una popolazione eterogenea che si trova in vari siti anatomici, tra cui il sacco vitellino (YS) e l'aorta-gonade-mesonefro (AGM). Comprende cellule che differiscono per il potenziale di sviluppo, definendo così programmi ematopoietici distinti. Nonostante la discendenza endoteliale delle cellule del sangue sia ben consolidata, l'identità di HE è ancora dibattuta. Una caratterizzazione più approfondita di HE è quindi essenziale per guidare gli sforzi nel derivare questa popolazione dalle cellule staminali pluripotenti umane (hPSC), un passaggio fondamentale per generare emoderivati terapeutici in vitro. Tuttavia, gli attuali marcatori noti utilizzati per isolare l'HE non sono sufficienti poiché arricchiscono anche le cellule arteriose associate. Per identificare specifici marcatori HE umani, abbiamo eseguito l'analisi trascrittomica di embrioni umani di 4-5 settimane, una fase di sviluppo caratterizzata da EHT attivo. Abbiamo identificato la codifica FCGR2B per il recettore Fc CD32, precedentemente associato ad altri endoteli specializzati, come gene arricchito nella popolazione ACE+CD34+ che contiene HE. Analisi funzionali ex vivo hanno confermato che il potenziale ematopoietico multilineare è altamente arricchito nelle cellule endoteliali CD32+ isolate dall'AGM e dall'YS di embrioni umani. Inoltre, CD32 è emerso come marcatore selettivo per HE derivato da hPSC in diversi programmi ematopoietici. Sorprendentemente, le nostre analisi hanno mostrato che la specificità del CD32 per le cellule con potenziale emogeno è superiore ad altri marcatori HE noti nelle colture ematopoietiche derivate da hPSC. Questi risultati forniscono un metodo semplice per isolare HE da embrioni umani e hPSC, consentendo la sua caratterizzazione molecolare e la generazione efficiente di cellule ematopoietiche in vitro.
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Stein, Sebastian [Verfasser]. "HSC-Kantenbearbeitung von Blech / Sebastian Stein." Aachen : Shaker, 2010. http://d-nb.info/1081884592/34.
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Zhou, Xuan. "RhoA GTPase Controls Cytokinesis and Programmed Necrosis of Hematopoietic Progenitors." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1378197381.
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Meiklejohn, Stuart J. "The role of BMP signalling in HSC ontogeny." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:305597a8-b8cb-42ff-88fd-34b3dd5bf39b.
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The haematopoietic stem cell (HSC) is found in the adult human bone marrow, where it gives rise to all the circulating blood cells throughout adulthood. Understanding the signalling events that programme these cells during development will improve HSC in vitro culture, their generation from embryonic stem cells or induced pluripotent stem cells, and their potential therapeutic application. HSCs bud from the floor of the dorsal aorta and seed the bone marrow via circulation. The precursors to the dorsal aorta and HSCs are called haemangioblasts, which are found in the dorsal lateral plate mesoderm in Xenopus. The knowledge of the location of these precursors allows their programming to be studied in detail during embryonic development. A key pathway implicated in the programming of HSCs is the BMP signalling pathway. Here, using both a small molecule inhibitor and a transgenic Xenopus line, BMP signalling has been inhibited post-gastrulation without perturbing the gross morphology of the embryo. This has shown that BMP signalling is required for HSC programming in the dorsal lateral plate mesoderm via the expression of a critical haematopoietic transcription factor, gata2. Morpholino knockdown of evi3has revealed it to be essential for HSC programming in the dorsal lateral plate mesoderm, where it is required for the expression of gata2. Furthermore, as evi3 is known to bind to the active BMP signalling complex, and as evi3 knockdown phenocopies post-gastrulation BMP inhibition, evi3 appears to be required for BMP signalling to initiate gata2 expression in the DLP. Taken together, the findings presented here demonstrate an essential post-gastrulation role of BMP signalling and Evi3 for programming HSCs in Xenopus.
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SIGHINOLFI, SILVIA. "INTRACELLULAR IRON OVERLOAD AFFECTS HSC METABOLISM BY IMPAIRING MITOCHONDRIAL FITNESS IN β-THALASSEMIA." Doctoral thesis, Università Vita-Salute San Raffaele, 2023. https://hdl.handle.net/20.500.11768/137019.
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Mitochondrial activity and metabolism significantly control hematopoietic stem cell (HSC) function and fate. HSCs change the metabolic state in response to stress signals, such as reactive oxygen species (ROS), which drive HSC entry into cell cycle accompanied by increased mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. However, excessive accumulation of ROS results in oxidative damage of cellular organelles, including mitochondria. Iron is one of the sources of ROS and HSCs can uptake iron but little is known about the effects of iron on HSC metabolism.
Recently, we demonstrated an impaired function of HSCs in β-Thalassemia (BThal), a condition of systemic iron overload (IO). We also observed that IO reduces the hematopoietic supportive capacity of BThal BM mesenchymal stromal cells. However, there is no evidence of the direct effect of IO on HSCs in BThal. We hypothesized that IO and the resulting oxidative stress could alter HSC metabolism and function.
We found a positive enrichment of iron homeostasis genes in HSCs from thalassemic th3 mice, suggesting increased iron uptake and storage. Consistently, we detected high levels of free reactive iron in the cytoplasm and in mitochondria of th3 HSCs, correlating with high ROS levels. As a result, mitochondria are impaired, with low mass and activity. Interestingly, th3 multipotent progenitors inherited dysfunctional mitochondria since the rescue of mitochondrial activity occurred in the transition to more committed progenitors. In line with mitochondrial dysfunction, th3 HSCs had reduced OXPHOS-derived ATP and relied on glycolysis. In vivo reduction of mitochondrial ROS rescued mitochondrial activity and metabolism, and increased th3 HSC frequency and quiescence, thus indicating that oxidative stress is the cause of mitochondrial dysfunction and potentially HSC defects. Importantly, in vivo administration of iron dextran to wt mice generated intracellular IO and mitochondrial oxidative stress and decreased mitochondrial activity in HSCs, indicating that IO alone is sufficient to impair mitochondria.
Our study unveils that IO directly impacts on HSC metabolism by inducing oxidative stress and mitochondrial dysfunction. Alterations in mitochondrial activity and metabolic profile, in response to IO, are expected to alter HSC function. This research will add novel insight about the role of iron in regulating HSC metabolism and provide clues for improving clinical conditions associated to IO, such as BThal.L'attività e il metabolismo mitocondriali controllano in modo significativo la funzione e il destino delle cellule staminali ematopoietiche (HSC). Le HSC modificano lo stato metabolico in risposta a segnali di stress, come le specie reattive dell'ossigeno (ROS), che guidano l'ingresso delle HSC nel ciclo cellulare accompagnato da un aumento della fosforilazione ossidativa mitocondriale (OXPHOS) e della glicolisi. Tuttavia, l'eccessivo accumulo di ROS provoca il danno ossidativo degli organelli cellulari, compresi i mitocondri. Il ferro è una delle fonti di ROS e le HSC possono assorbire il ferro, ma si sa poco sugli effetti del ferro sul metabolismo delle HSC. Recentemente, abbiamo dimostrato una funzione alterata delle HSC nella β-talassemia (BThal), una condizione di sovraccarico sistemico di ferro (IO). Abbiamo anche osservato che l'eccesso di ferro riduce la capacità di supporto ematopoietica delle cellule stromali mesenchimali talassemiche. Tuttavia, non ci sono prove dell'effetto diretto del sovraccarico di ferro sulle HSC in BThal. Abbiamo ipotizzato che il sovraccarico di ferro e il conseguente stress ossidativo alterino il metabolismo e la funzione delle HSC. Abbiamo trovato un arricchimento positivo dei geni dell'omeostasi del ferro nelle HSC dei topi talassemici th3, suggerendo un aumento dell'assorbimento e dell'immagazzinamento del ferro. Coerentemente, abbiamo rilevato alti livelli di ferro reattivo libero nel citoplasma e nei mitocondri di th3 HSC, che correlano con alti livelli di ROS. Di conseguenza, i mitocondri sono alterati, con ridotta massa e attività. I progenitori multipotenti th3 hanno ereditato mitocondri disfunzionali poiché la correzione dell'attività mitocondriale si è verificata nella transizione verso progenitori più differenziati. In linea con la disfunzione mitocondriale, le HSC th3 hanno una ridotta produzione di ATP mediante OXPHOS e dipendono dalla glicolisi. La riduzione in vivo dei ROS mitocondriali ha ripristinato l'attività e il metabolismo mitocondriali e ha aumentato la frequenza e la quiescenza delle HSC th3, dimostrando così che lo stress ossidativo è la causa della disfunzione mitocondriale e dei potenziali difetti delle HSC. È importante sottolineare che la somministrazione in vivo di ferro destrano a topi wt ha generato eccesso di ferro intracellulare e stress ossidativo mitocondriale e una ridotta attività mitocondriale nelle HSC, indicando che il sovraccarico di ferro da solo è sufficiente per compromettere i mitocondri. Il nostro studio rivela che il sovraccarico di ferro ha un impatto diretto sul metabolismo delle HSC inducendo stress ossidativo e disfunzione mitocondriale. Le alterazioni dell'attività mitocondriale e del profilo metabolico, in risposta al sovraccarico di ferro, potrebbero alterare la funzione delle HSC. Questa ricerca aggiungerà nuove informazioni sul ruolo del ferro nella regolazione del metabolismo delle HSC e fornirà nuove conoscenze utili per migliorare le condizioni cliniche caratterizzate da sovraccarico di ferro, come BThal.
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Sahm, Alexander [Verfasser]. "Prognose der Schnittkräfte bei der HSC-Bearbeitung / Alexander Sahm." Aachen : Shaker, 2003. http://d-nb.info/1174513950/34.
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Bonkhofer, Florian. "Identification of novel Runx1 targets involved in HSC development." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:4badf9f4-f796-4063-8176-dd57644fd811.
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Haematopoietic stem and progenitor cells (HSPCs) are de novo generated within in the ventral aspects of the embryonic dorsal aorta (DA). Cells of this haemogenic endothelium (HE) will eventually undergo an endothelial to haematopoietic transition (EHT) that involves cell budding out of the aortic wall. Despite the detailed description of the cellular events, the exact haemogenic lineage path and the underlying molecular mechanism that establish full haematopoietic competence are still not entirely understood. The transcription factor Runx1 is critical for the emergence of HSPCs and shows expression in the zebrafish HE as early as 24 hpf. To facilitate a detailed analysis of the transient HE population I generated a TgBAC(runx1P2:Citrine) reporter line under the control of the endogenous runx1 promoter on a bacterial artificial chromosome (BAC). Double-transgenic reporter lines for runx1 and the endothelial marker kdrl allowed us to isolate specifically cells of the DA away from the whole endothelial population, which could be further sub-divided into HE and non-haemogenic cells. Genomewide expression analysis within the respective tissues and upon Runx1 loss of function enabled the identification of HE-specific Runx1-regulated genes. Hereby, the gfi1ab gene appeared as the functional homologue of the murine Gfi1. I show that in zebrafish, EHT is orchestrated through a conserved Runx1-Gfi1-Lsd1 axis. The cellular functions of the remaining Runx1 targets imply that maturation into fully functional HSCs depends on epigenetic regulation due to the up-regulation of de novo DNAmethyltransferases, as well as on factors that allow the developing HSCs to respond to extrinsic cues from haematopoietic niches. Lastly, it became evident that the early HE expresses dll4 at similar levels to the rest of the aortic endothelium, indicating a common lineage path. In the absence of RUNX1 the HE remains essentially arterial and persists as an integrated part of the DA.
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Hotakainen, L. (Lari). "HSC-3 -solujen eksosomit ja CAV-1 -proteiinin ilmeneminen." University of Oulu, 2017. http://urn.fi/URN:NBN:fi:oulu-201705312281.
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Kielisyövän tuumorimikroympäristö ja sen eri komponentit ovat olleet viime aikoina kiivaan tutkimuksen kohteena. Näillä tekijöillä näyttäisi olevan merkitystä syövän kasvussa, invaasiossa ja leviämisessä. Mikroympäristön ominaisuuksiin vaikuttaa todennäköisesti syöpäsolujen ja tuumorin mikroympäristön molekyylivälitteinen keskustelu, ja tämän vuoropuhelun viestinvälittäjiä ovat esimerkiksi eksosomit. Eksosomit ovat kehon normaalien solujen ja syöpäsolujen erittämiä lipidikaksoiskalvollisia mikrovesikkeleitä, jotka voivat spesifisesti sitoutua kohdesoluunsa, ja muokata sen toimintaa esimerkiksi sen sisältämien proteiinien ja RNA:n välityksellä. Syöpäsolujen eksosomien kohdesoluina voivat olla esimerkiksi mesenkymaaliset kantasolut, tulehdussolut tai ns. syöpään liittyvät fibroblastit (CAFs, cancer associated fibroblasts). Kielisyövän on havaittu ilmentävän normaalia enemmän kaveoliini-1 -proteiinia (CAV-1), jonka määrä näyttäisi nousevan syövän kehitysasteen mukaan. Tässä tutkimuksessa selvitimme in vitro -laboratoriokokeilla, sisältävätkö aggressiivisen liikkuvan kielen syöpäsolulinjan (HSC-3) erittämät eksosomit CAV-1 proteiinia.
Tutkimuksiemme alkuvaiheessa loimme pohjaa eksosomieristyksen menetelmille yhteistyössä israelilaisen tutkimusryhmän kanssa. Varsinaisessa tutkimuksissamme eristimme eksosomeja HSC-3 solulinjalta käyttäen kaupallista ExoQuick-TC™ -valmistetta. Solujen eksosomieritystä indusoitiin käyttäen 4-aminofenyylielohopea-asetaattia (APMA). Kerättyjä eksosomeja ja sen sisältämiä proteiineja (CD63 ja CAV-1) tarkasteltiin immunoelektronimikroskopialla sekä Western blot -analyysillä.
Sekä immunoelektronimikroskopiassa että Western blot -analyysissä havaittiin eristettyjen eksosomien sisältävän niille tyypillistä CD63-proteiinia sekä CAV-1 -proteiinia. Saamamme tulokset viittaavat siihen, että kielisyöpäsolut saattavat olla osana CAV-1-proteiinin kertymissä tuumorin mikroympäristöön. Tällä saattaa olla merkitystä mikroympäristön muuttumisessa edullisemmaksi syövän jakaantumiselle, invaasiolle ja leviämiselle. Vaikka tutkimuksemme osoittavat eksosomien ja CAV-1-proteiinin yhteyden, tarvitaan lisätutkimuksia myös näiden kahden yhteydestä sekä in vitro -kokeissa muilla kielisyöpäsolulinjoilla että in vivo -kielisyöpätutkimuksissa. CAV-1 proteiinin rooli syövän kehityksessä on monimutkainen ja osin epäselvä, ja tämänhetkiset tutkimustulokset ovatkin osin ristiriidassa keskenään. Myös eksosomien ja CAV-1 proteiinin erityksen säätely solutasolla vaatii lisätutkimuksia. Tulokset kuuluvat BMC Cancer -lehdessä julkaistuun alkuperäisartikkeliin, jossa allekirjoittaneen työpanos on käsitelty tiivistelmäosuudessa.
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Enk, Dirk. "Untersuchungen zum dynamischen Stabilitätsverhalten von Fräswerkzeugen zur HSC-Bearbeitung." Essen Vulkan-Verl, 2009. http://d-nb.info/995794677/04.
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Sakamaki, Taro. "Hoxb5 defines the heterogeneity of self-renewal capacity in the hematopoietic stem cell compartment." Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/263564.
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Ghiaur, Gabriel. "The role of Rho GTPases in hematopoietic stem cell biology RhoA GTPase regulates adult HSC engraftment and Rac1 GTPases is important for embryonic HSC /." Cincinnati, Ohio : University of Cincinnati, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1204374567.
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Zayas, Jennifer. "Regulation of HSC Self-Renewal and Differentiation by Pumilio Proteins." Scholarly Repository, 2008. http://scholarlyrepository.miami.edu/oa_dissertations/300.
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Evolutionarily conserved Pumilio (Pum) RNA-binding proteins act as translational repressors during embryo development and cell fate specification. Previous work in the lab has shown that over-expression of Pum2 (Pum2-EML) supports maintenance and suppresses mutilineage differentiation of murine multipotent HSC/MPP-like cell line EML. The subsequent analysis of HSC markers and functional analysis has revealed that wt EML cells share the LKS CD34 positive phenotype, whereas the majority Pum2-EML cells are similar to LKS CD34 negative. The CD34 positive wt EML cells can be divided into CD34low, CD34med and CD34high subpopulations, whereas Pum2-EML CD34 positive cells correspond to CD34low subpopulation. Colony forming assays have revealed that the overall multilineage differentiation of wt EML and Pum2-EML cells strongly correlates with the CD34 expression levels. Multiple experiments have revealed that purified CD34 negative and CD34 positive wt EML cells can generate each other and among CD34 positive wt EML cells the CD34low cells have the highest capacity to give rise to CD34 negative EML cells. We have proposed a model in which CD34 negative EML cells are more primitive cells in an "inactive" (differentiation inhibited) state, that give rise to CD3low "active" (differentiation ready) EML cells. The CD34low EML cells can revert back to the CD34 negative state or give rise to CD34med/high cells that can readily differentiate into multiple lineages. Based on that model, the over-expression of Pum2 leads to increased maintenance of cells in inactive CD34 negative state, and blocks development of CD34 positive cells past the CD34low stage. Cumulatively, these results support the notions that Pum2 could be involved in maintaining the balance between inactive and active state of multipotent hematopoietic cells. The c-kit receptor plays a vital role in self-renewal and differentiation of hematopoietic stem cells (HSC) and multipotent progenitors (MPPs). We have discovered that besides c-kit, the murine multipotent HSC/MPP-like cell line EML expresses the transcript and protein for a truncated form of c-kit, called tr-kit. Notably, the tr-kit transcript and protein levels were down-regulated during cytokine induced differentiation of HSC/MPP-like cell line EML into myelo-erythroid lineages. RT-PCR results show tr-kit is transcribed solely in cell populations enriched for LTR-HSC, STR-HSC and MPPs. The observation that tr-kit is co-expressed with c-kit only in more primitive, HSC and MPP-enriched cell populations raises an exciting possibility that tr-kit functions either as a new component of SCF/c-kit pathway, or is involved in a novel signaling pathway, present exclusively in HSC and MPPs. These findings necessitate functional characterization of tr-kit, and analysis of its potential role in the self-renewal, proliferation and/or differentiation of HSC and multipotent progenitors.
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Munirathnam, Madhu. "Einfluss masseoptimierter Kragarmstrukturen auf die dynamische Bahngenauigkeit von HSC-Fräsmaschinen /." Aachen : Shaker, 2008. http://d-nb.info/990312801/04.
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Stroh, Carsten. "Über die Spline-basierte Werkzeugweggenerierung für die HSC-Schlichtbearbeitung von Freiformflächen /." Aachen : Shaker, 2008. http://d-nb.info/989297888/04.
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Söderling, Filip. "Structural analysis of HSC hull design for JFD swimmer delivery system." Thesis, KTH, Marina system, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-234836.
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Fiber composites are widely used for small high-speed crafts due to their high strength to weight ratio. James Fisher Defense (JFD) has developed a high-speed swimmer delivery system called SEAL Carrier which is built upon a carbon fiber structure. The SEAL Carrier structure is designed according to Det Norske Veritas (DNV) rules for classification from 2011. Since the merge between DNV and Germanischer Lloyd (GL), a harmonization of the rule sets was per-formed and in 2016 a new set of rules were adopted. The analysis carried out in this thesis aims to give an understanding for JFD how their hull structure relates to the new set of rules. A number of weak structural members was identified, which raised questions about the effects of the changes in the rule sets. For some panel fields the lateral deflection differed up to 500%and it was also shown that the criteria for maximum stress differs up to 42%. This analysis will be used as support in the further development of new series of SEAL Carrier which might be classified by DNV-GL. The author proposes material tests to avoid uncertainties discussed in the report, together with higher level of detail in the structural arrangement to decrease the margin of error.Kompositmaterial är vida använt som material för mindre snabbgående fartyg, tack vare dess styrka relativt vikt. James Fisher Defence har tagit fram ett dykartransportsystem kallat SEAL Carrier vars skrov är byggt av kolfiber. Det ursprungliga skrovet är designat utifrån regelver-ket av Det Norske Veritas (DNV) från 2011. Analysen i denna rapport har som mål att identifiera hur väl detta skrov står sig mot en uppdateringen av regelverket från 2011. Ett antal struk-turella delar har visat sig inte uppnå designkraven som ställs i detta regelverk, vilket väckte in-tresse för vad som faktiskt skiljer sig mellan utgåvorna. Sedan sammanslagningen mellan DNV och Germanischer Lloyd (GL) har en harmoniserad gemensam utgåva av regelverket publicerats 2016. För vissa paneler har resultaten visat att regelverken skiljer sig upp mot 500% samt att ett kriterium gällande maximal tillåten stress skiljer sig upp till 42%. Denna analys kommer att behandlas som underlag för en vidareutveckling utav nästa generations SEAL Carrier, vilken kan komma att certifieras av DNV-GL. Författaren föreslår materialtester för att undvika os-äkerheter beskrivna i rapporten, tillsammans med högre detaljnivå i skrovkonstruktion för att minska felmarginalen i analysen.
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Dresselhaus, Manfred. "Ein Mustererkennungssystem für bildverarbeitungsgestützte Robotikaufgaben auf der Basis des hierarchischen Strukturcodes HSC /." Düsseldorf : VDI-Verl, 1991. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=002720084&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
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Dixon, Wendy P. "Selection procedures relating to Australian vocal repertoire for mid-adolescent HSC performers." University of Sydney, 2007. http://hdl.handle.net/2123/1590.
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Master of Music (Music Education)This thesis documents an investigation of the selection procedures relating to Australian vocal repertoire for mid-adolescent and Higher School Certificate (New South Wales) performers, as used by private singing teachers, school music teachers and singing students. It explores the similarities and differences in the criteria employed in these selections. Semi-structured interviews were the source of data and were conducted with participants from these three categories as well as two composers. The participants evinced highly disparate views. The private singing teachers believed that repertoire should be dictated by the technical ability and physiological constraints of mid-adolescent students and that their role in selecting repertoire was related to the long term vocal growth of each individual. They felt that the school music teachers vetted their repertoire choices with no useful explanation of their reasoning, while the school music teachers noted that students frequently presented repertoire that was too difficult or that was not readily communicated with the audience. The ability of mid-adolescent singers to communicate with and engage an audience was the prime concern of the school music teachers. The students wanted to impress their examiners and believed that infrequently heard repertoire was the best choice, though this was not endorsed by the teachers. There was a perception that the students would perform at their best when they chose repertoire to which they could relate emotionally. Many private singing teachers and school music teachers are not aware of the very broad range of contemporary Australian music and its divergent characteristics. However, there is a shortage of appropriate Australian repertoire that addresses the physiological and emotional needs of mid-adolescent singers.
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Munirathnam, Madhu [Verfasser]. "Einfluss masseoptimierter Kragarmstrukturen auf die dynamische Bahngenauigkeit von HSC-Fräsmaschinen / Madhu Munirathnam." Aachen : Shaker, 2008. http://d-nb.info/1161304029/34.
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Dixon, Wendy. "Selection procedures relating to Australian vocal repertoire for mid-adolescent HSC performers." Connect to full text, 2006. http://hdl.handle.net/2123/1590.
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Thesis (M. Mus. (Mus. Ed.)--University of Sydney, 2006.Title from title screen (viewed 19 March 2008). Submitted in fulfilment of the requirements for the degree of Master of Music (Music Education) to the Sydney Conservatorium of Music. Includes bibliographical references. Also issued in print format.
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McGraw, Kelli. "Innovation and change in the 1999 NSW HSC English syllabus: Challenges and problems." Thesis, The University of Sydney, 2010. http://hdl.handle.net/2123/16459.
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The purpose of this doctoral research is to analyse the 1999 NSW HSC English syllabus through the lens of its reception and implementation, to produce an account of the theoretical changes that are embedded in the syllabus documents and the impact that these changes had on selected stakeholders. The findings made about the 1999 HSC English syllabus are discussed in relation to Hunter’s genealogy of the functions of schooling (1993), to explore the desired purposes of schooling reflected in both the English curriculum, and in stakeholder’s attitudes. Using grounded theory methods in a qualitative approach to exploring the experiences of teachers at two schools through interview and observation data, as well as an analysis of the reactions represented in the public through newspaper publications from 1995-2005, core categories of experience and concern are identified relating to the implementation of the mainstream mandatory courses in English for the HSC. These core categories are used as a basis for a content analysis of key extracts of the English syllabus, with the finding that curriculum changes such as the inclusion of visual texts and language modes constituted an important theoretical shift in the content and objectives of English as a school subject. Also, while some challenges faced by stakeholders are seen to arise from problematic constructions of English in the syllabus itself, other tensions can be seen to be based on the particular demands of the local school contexts, and intensified by pressure from largely negative newspaper portrayals of English teachers and curriculum.
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Vincent, Karen Jane. "Studies on the expression and regulation of transcription factors in hepatic stellate cells." Thesis, University of Southampton, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323790.
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Stroh, Carsten [Verfasser]. "Über die Spline-basierte Werkzeugweggenerierung für die HSC-Schlichtbearbeitung von Freiformflächen / Carsten Stroh." Aachen : Shaker, 2008. http://d-nb.info/1162792590/34.
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McGraw, Kelli. "Innovation and change in the 1999 NSW HSC English syllabus: Challenges and problems." Thesis, University of Sydney, 2010. https://eprints.qut.edu.au/114957/1/114957.pdf.
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The purpose of this doctoral research is to analyse the 1999 NSW HSC English syllabus through the lens of its reception and implementation, to produce an account of the theoretical changes that are embedded in the syllabus documents and the impact that these changes had on selected stakeholders. The findings made about the 1999 HSC English syllabus are discussed in relation to Hunter’s genealogy of the functions of schooling (1993), to explore the desired purposes of schooling reflected in both the English curriculum, and in stakeholder’s attitudes. Using grounded theory methods in a qualitative approach to exploring the experiences of teachers at two schools through interview and observation data, as well as an analysis of the reactions represented in the public through newspaper publications from 1995-2005, core categories of experience and concern are identified relating to the implementation of the mainstream mandatory courses in English for the HSC. These core categories are used as a basis for a content analysis of key extracts of the English syllabus, with the finding that curriculum changes such as the inclusion of visual texts and language modes constituted an important theoretical shift in the content and objectives of English as a school subject. Also, while some challenges faced by stakeholders are seen to arise from problematic constructions of English in the syllabus itself, other tensions can be seen to be based on the particular demands of the local school contexts, and intensified by pressure from largely negative newspaper portrayals of English teachers and curriculum.
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Zhou, Xiang. "Expressions of hsc/hsp70 cDNAs in bacteria and comparison with tissue-isolated proteins." Thesis, The University of Arizona, 1993. http://hdl.handle.net/10150/144636.
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Rat hsc70 and human hsp70 have been expressed in bacteria using the T7 polymerase system. The recombinant proteins, which were the major proteins in E.coli, had the same molecular weights as the tissue-isolated proteins and were immunoactive with hsc70/hsp70 antibodies. ATP binding assay by equilibrium dialysis showed a K$\sb{\rm d}$ for ATP of 0.44 $\mu$M. At saturation, 0.4 mole of ATP was bound per mole of hsc70. Both recombinant and tissue-isolated hsc70/hsp70 have ATPase activities. The denatured substrate, reduced carboxyl methylated $\alpha$-lactalbumin (RCMLA), stimulated ATPase rates of bovine tissue-isolated hsc70/hsp70, but the ATPase rates of rat skeletal muscle and recombinant hsc70 were not changed upon the adding of RCMLA. The analysis of two-dimensional gels showed hsc70/hsp70 isolated from different sources had different isoform patterns. It is speculated that each isoform may have its own substrate specificity.
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Tanaka, Masayuki, Kenneth C. Wong, Anupreeta More, Arsha Dezuka, Eiichi Egami, Masamune Oguri, Sherry H. Suyu, et al. "A SPECTROSCOPICALLY CONFIRMED DOUBLE SOURCE PLANE LENS SYSTEM IN THE HYPER SUPRIME-CAM SUBARU STRATEGIC PROGRAM." IOP PUBLISHING LTD, 2016. http://hdl.handle.net/10150/621400.
Full textAbstract:
We report the serendipitous discovery of HSC J142449-005322, a double source plane lens system in the Hyper Suprime-Cam Subaru Strategic Program. We dub the system Eye of Horus. The lens galaxy is a very massive early-type galaxy with stellar mass of similar to 7 x 10(11) M-circle dot located at z(L) = 0.795. The system exhibits two arcs/rings with clearly different colors, including several knots. We have performed spectroscopic follow-up observations of the system with FIRE on Magellan. The outer ring is confirmed at z(S2) = 1.988 with multiple emission lines, while the inner arc and counterimage is confirmed at z(S1) = 1.302. This makes it the first double source plane system with spectroscopic redshifts of both sources. Interestingly, redshifts of two of the knots embedded in the outer ring are found to be offset by Delta z = 0.002 from the other knots, suggesting that the outer ring consists of at least two distinct components in the source plane. We perform lens modeling with two independent codes and successfully reproduce the main features of the system. However, two of the lensed sources separated by similar to 0.7 arcsec cannot be reproduced by a smooth potential, and the addition of substructure to the lens potential is required to reproduce them. Higher-resolution imaging of the system will help decipher the origin of this lensing feature and potentially detect the substructure.
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Huerga, Encabo Hector 1989. "Analysis of transcription mechanisms that limit type I interferon responses." Doctoral thesis, Universitat Pompeu Fabra, 2018. http://hdl.handle.net/10803/666035.
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Nicholson, Philippa Ruth. "The roles of Shc, PPZA and Hsc 70 binding in transformation by polyoma middle-T antigen." Thesis, Imperial College London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.252110.
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Nafi, Valencia Erika. "The role of hsc-70 in very low density lipoprotein tranport vesicle golgi fusion complex formation." Honors in the Major Thesis, University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/592.
Full textAbstract:
Excess production and secretion of very low-density lipoprotein (VLDL) by the liver into the circulatory system is directly related to atherosclerosis, a chronic cardiovascular disease that threatens the lives of many worldwide and continues to be a leading cause of death in the United States. The rate-limiting step in VLDL secretion is its transport from the site of biogenesis, the hepatic endoplasmic reticulum to the cis-Golgi. This step is mediated by a specialized ER- derived vesicle, the VLDL transport vesicle (VTV). Upon exit of the ER the VTV targets, fuses and delivers VLDL into the lumen of the Golgi. The targeting and fusion of the VTV with the Golgi is facilitated by specific set of soluable N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins that form a SNARE complex, which is required for the VTV-Golgi fusion and thus delivery to the Golgi. Data from our laboratory indicates that the formation of the SNARE complex requires cytosolic factors. Through the purification of liver cytosol, chromatographic steps, detailed mass spectrometry, immunodepletion and western blotting data it was identified that the protein necessary for SNARE complex formation is Hsc-70. Although Hsc-70's identification is significant, the role it plays in SNARE complex formation for VTV -Golgi fusion is a predicament and yet to be unraveled. In this study we performed a series of co-immunoprecipitation reactions to identify its role in SNARE-complex assembly. Using western blot data we confirmed binding of Hsc-70 with Sec22b, the v-SNARE on the VTV. Moreover, we confirmed the interaction of Hsc-70 with t-SNAREs, (syn5, rBet1 and GOS28) on the Golgi membrane. Removal of Hsc-70 from the liver cytosol resulted in significant reduction of SNARE-complex formation. Ultimately, the identification proteins involved in the process of VLDL delivery to the Golgi would offer therapeutic targets to control VLDL secretion into the blood by the liver.B.S.
Bachelors
Burnett School of Biomedical Sciences
Molecular Biology and Microbiology
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MALLARDO, MARIA. "DISSECTING THE ROLE OF THE CYTOPLASMIC MUTANT NUCLEOPHOSMIN IN ACUTE MYELOID LEUKAEMIA DEVELOPMENT." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/234152.
Full textAbstract:
Acute myeloid leukaemia (AML) is a genetic heterogeneous group of diseases, with the largest subgroup showing a mutation in the Nucleophosmin gene (NPM1). Normally the NPM protein localizes mainly in the nucleolus, but in AML blasts it is aberrant localized to the cytoplasm (NPMc+AML). Notably, NPMc+AML patients show peculiar gene expression profiles, treatment response and prognosis. Hence, it has been proposed as an independent category for leukaemia classification according to WHO in 2008. In view of the relevance of NPMc+ mutation to AML pathogenesis and prognosis, understanding its role in leukaemia development represents a major issue in the field.
The aim of this PhD project is to get further insight into the relevance of NPMc+ mutations to AML development. To this scope, here it is reported a characterization of a novel mouse model expressing the mutated protein. The hematopoietic restricted expression of the protein induces leukaemia in mice. This data definitively clarify that NPMc+ is an initiating mutation for leukaemia development. However, the long latency and low penetrance of disease onset strongly support the need of cooperating mutations. Since, the high frequency of FLT3-ITD mutations in NPMc+AML, we genetically tested the synergisms between the two abnormalities. To this scope, NPMc+ mice were crossed with FLT3-ITD mice (Lee, 2007). Double mutated mice developed leukaemia with sort latency and full penetrance indicating effective cooperation. Moreover, our data support the two hits model of tumourigenesis, where functional complementary mutations contribute to disease onset.
Another major challenge of this project is to understand how NPMc+ affect the biology of normal HSPC and imposes the transition from normal to cancer stem cells. We found that NPMc+ expression perturbs the homeostasis of HSCP and expand the number of LT-HSC by increasing the proliferation rate. However, this enhanced proliferation is not associated to loss of quiescent and functional HSC, which may represent a reservoir of persistent pre-malignant cells available for the accumulation of additional genetic alteration. Further investigation into the biology of per-leukaemic stem cells may give insights into the molecular mechanisms imposed by the oncogene for malignancy transformation and finally may contribute for the development of new therapeutic strategies.
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Lendínez, Javier González. "Unravelling a new role of Notch signalling pathway in HSC development using a Hes1-EGFP mouse model." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25897.
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In the mid-gestation embryo, the first definitive transplantable hematopoietic stem cells (dHSCs) emerge by embryonic day E10.5-E11 in the aorta-gonadomesonephros (AGM) region, as a result of a step-wise maturation of precursors called pre-HSCs. The analysis of several Notch mutants suggests that Notch signalling is essential for the execution of the definitive hematopoietic programme in the AGM. Mouse embryos deficient for Notch1, RBP-Jk or Jagged1 cannot efficiently generate intra-embryonic hematopoeitic progenitors. It has also been reported that knockdown of Notch target genes (Hes1, Hes5) results in hematopoietic impairment. However a clear picture of the role of Notch pathway in HSC development is still missing. In this work we characterised precise stages and cell types during HSC development in which Notch signalling is involved. First we used a Hes1-dEGFP reporter mouse line that allowed us to monitor Notch pathway activity in a narrow window of time. The results suggest that the level of Notch activity fluctuates in HSC lineage in the AGM region and is down-regulated in dHSCs in the foetal liver (where dHSCs migrate after generation in the AGM region). By using transplantation assay, we further showed that fluctuations of Notch activity are essential for HSC development, and that this pattern in the HSC lineage might work as a switch between maturation and proliferation of PreHSC1, PreHSC2 and dHSC, in which temporary decrease might be required to mature from one type to another, both in vitro and in vivo. These findings might need to be taken into consideration for in vitro generation of haematopoietic stem cells, where a fine tuning of Notch signalling activity could greatly improve their emergence.
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Barria, Emily Alpas. "HSC differentiation is fleeting, but self-renewal is forever : in vitro self-renewal of hematopoietic stem cells /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2004. http://wwwlib.umi.com/cr/ucsd/fullcit?p3123666.
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Jing, Duohui. "Mobilisation, Isolation and Coculture of Haematopoietic Stem Cells." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-39915.
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Since decades, hematopoietic stem cell transplantation (HSCT) has become a well established treatment modality for hematological malignancies and non-malignant disorders. Autologous and allogeneic hematopoietic stem cells (HSCs) mobilized into the peripheral blood (PB) have been used as a preferred source of transplantable stem cells1-3. And umbilical cord blood (UCB) has been introduced as a more attractive HSC source for HSCT, because fetal stem cells in UCB are speculated to be more primitive in comparison to adult stem cells. However the limited amount of HSCs is limiting their application for stem cell therapy in clinic. Therefore, people started to utilize extra-embryonic tissue to harvest more fetal stem cells, while people also tried to optimize the clinical protocol to mobilize more adult stem cells out of adult bone marrow. The innovative strategies and feasible procedures were discussed in this thesis.
The axis of the chemokine receptor CXCR4 and its ligand SDF-1 is important for trafficking and homing of HSCs. It has already been demonstrated that the bicyclam AMD3100, a CXCR4 antagonist, in combination with G-CSF is able to induce a significant mobilization of CD34+ cells4. And human placenta is a potent hematopoietic niche containing hematopoietic stem and progenitor cells throughout development5. The homing of HSCs to the placenta is probably also mediated by the expression of SDF-1 as demonstrated for the bone marrow niche. In this study (part 1 of the chapter “Results and discussions”), we utilized AMD3100 to mobilize HSCs from placenta. And we can demonstrate that the CXCR4 antagonist AMD3100 mobilise placenta derived CD34+ cells ex utero already after 30 min of incubation and may further enhance the efficacy of harvesting placenta-derived HSC.
The alpha4 integrin CD49d is involved in migration and homing of hematopoietic stem cells (HSC). Therapeutic application of natalizumab, an anti-CD49d antibody, in patients with multiple sclerosis (MS) has been associated with increased levels of circulating CD34+ progenitors. In our study (part 2 of the chapter “Results and discussions”), we compared circulating HSCs from MS patients after natalizumab treatment and HSCs mobilized by G-CSF in healthy volunteers, with regard to their migratory potential, clonogenicity and gene expression. CD34+ cells in the blood and marrow of natalizumab-treated patients expressed less of the stem cell marker CD133, were enriched for erythroid progenitors (CFU-E) and expressed lower levels of adhesion molecules. The level of surface CXCR-4 expression on CD34+ cells from patients treated with natalizumab was higher compared to that of CD34+ cells mobilized by granulocyte-colony stimulating factor (G-CSF) (median 43.9% vs. 15.1%). This was associated with a more than doubled migration capacity towards a chemokine stimulus. Furthermore, CD34+ cells mobilized by natalizumab contained more m-RNA for p21 and less MMP9 compared to G-CSF mobilised HSC. Our data indicate that G-CSF and CD49d blockade mobilize different HSC subsets and suggest that both strategies may be differentially applied in specific cell therapy approaches.
In order to further improve the clinical outcome of HSC transplantation, many groups are focusing on ex vivo maintain or expand HSC. Unfortunately, the maintenance of HSC in vitro is difficult to achieve because of their differentiation. This is presumably caused by a lack of appropriate cues that are provided in vivo by the microenvironment. Indeed, HSCs located in the bone marrow are interacting with a specific microenvironment referred to as the stem cell niche, which regulates their fate in terms of quiescence, self-renewal and differentiation. An orchestra of signals mediated by soluble factors and/or cell-to-cell contact keeps the balance and homeostasis of self-renewal, proliferation and differentiation in vivo. To investigate the communication between HSCs and the niche, coculture assays with mesenchymal stromal cells (MSCs) were performed in vitro. Here, we can demonstrate that cell-to-cell contact has a significant impact on hematopoietic stem cells expansion, migratory potential and stemness. In this study (part 3 of the chapter “Results and discussions”), we investigated in more detail the spatial relationship between hematopoietic stem cells and mesenchymal stromal cells during ex-vivo expansion. And we defined three distinct localizations of HSCs relative to MSC layer: (i) those in supernatant (non-adherent cells); (ii) cells adhering on the surface of mesenchymal stromal cells (phase-bright cells) and (iii) cells beneath the mesenchymal stromal cells (phase-dim cells). Our data suggest that the mesenchymal stromal cell surface is the dominant location where hematopoietic stem cells proliferate, whereas the compartment beneath the mesenchymal stromal cell layer seems to be mimicking the stem cell niche for more immature cells. Our data provide novel insight into the construction and function of three-dimensional HSC–MSC microenvironments.
In summary, we provided a new method to isolate fetal stem cells from extra-embryonic tissue (i.e. placenta) in the first part, then we discussed an innovative strategy with CD49d blockade to improve clinical modality for adult stem cell mobilization in the second part, and finally we investigated HSC maintenance and expansion in vitro and provided feasible way to mimic HSC niche in vitro in the last part.
This thesis contributes to HSC-based stem cell therapy in two aspects, i.e. 1) fetal and adult stem cell isolation holding great therapeutic potential for blood diseases; 2) ex vivo stem cell manipulation providing a valuable platform to model HSC niche regulation.
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Weber, Lauren. "Reading the Curriculum: Empathic Education in Shakespeare, Keats and Haddon." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/25983.
Full textAbstract:
Abstract: In this thesis I argue that a complex approach to empathy is integral to subject English, especially in the twenty-first century. I begin my argument by showing how empathy has rhetorical power in contemporary society and the current New South Wales senior English curriculum. I contrast the way these discourses value empathy by mapping how empathy features in literature throughout educational and literary history. I show how literature provides complicated and conflicting examples of the way empathy operates between people and texts by offering three unique approaches to empathic literary criticism informed by interdisciplinary methodologies. My thesis makes an original contribution by demonstrating how empathy may work as a type of literary criticism and simultaneously as a form of resistance to the pressures and harmful effects of over-systematised education.
In the Introduction, I provide an overview of empathy’s multiple meanings to argue for a broad and multifaceted approach to empathy that resists a static definition. In Chapter 1, I propose the term 'pop empathy' to explain how empathy is wielded rhetorically in contemporary discourse involving politics, marketing and advertising, and artificial intelligence. I argue this is important because it influences the broader discourse involving empathy and affects its value in education.
Chapter 2 outlines the way current educational policy and curriculum documents rhetorically value empathy. I show how the reality of educational inequality in Australia complicates the way curriculum and policy documents claim to value empathy in education and that empathy in education is coming to be defined by pop empathy. Chapter 2 sets up my argument against the increasing influence of standardised and systematised education especially in subject English where empathy is cited directly as a potential outcome of study.
Chapters 1 and 2 work together to frame my theoretical approach to Chapters 3, 4, and 5 where I read three set texts belonging to different genres prescribed on the current NSW
senior English curriculum: Shakespeare's Hamlet, the poetry of John Keats, and Mark Haddon's The Curious Incident of the Dog in the Night-Time. I complicate and contribute to debates about the empathic value of subject English by highlighting the way these texts represent empathy. I examine empathy's relationship to the educational concerns of the Tudor period, the Romantic era, and the twenty-first century to build a historical view of empathy for the study of literature. The authors and texts studied in this thesis bear the mark of empathic pedagogy and as a result they offer unique impressions of empathy's make-up and capabilities. Through my readings I show how empathy has consistently featured in literary studies across time periods and genres while simultaneously complicating popular rhetorical uses of empathy. I address this wide scope of historical and generic texts as they relate to the NSW curriculum because I argue for a new approach to integrating empathy into subject English that privileges empathy as a form of critical interpretation rather than a student outcome.
In the Conclusion I draw together my rhetorical arguments and critical readings to show how a complex and open-ended approach to empathy without the pressure of predetermined outcomes can enrich the understanding of texts and the importance of studying literature. I offer directions for future research in the area of empathy and literary education to highlight how the project of exploring empathy in subject English is far from over.
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Stosich, Michael Steven. "MICRO-CT EVALUATION OF MSC/HUVEC/HSC-MEDIATED ANGIOGENESIS IN LARGE PCL-ßTCP CONSTRUCTS IMPLANTED IN NUDE MICE." Master's thesis, Temple University Libraries, 2011. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/213128.
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Oral BiologyM.S.
Stable vascular networks are prerequisite for scaffold-guided reconstruction of large voluminous bony defects. However, induction of angiogenesis remains a major challenge for bone-tissue engineering. The present in vivo study evaluates human umbilical cord derived vascular endothelial cells (HUVEC) or hematopoietic stem cells(HSCs)-mediated formation of microvascular networks in a biocompatible PCL-ßTCP hybrid scaffold in an immuno-compromised nude mouse. The PCL-ßTCP scaffold (30% PCL: 70% ßTCP; 70% porosity) with interconnected open pores was fabricated in 6x6x6mm cubes. They were seeded with human mesenchymal stem cells (MSCs) plus HUVECs or HSCs. Groups (N=12) consisted of scaffold samples seeded with MSCs alone, MSCs and HUVECs, MSCs and HSCs, and no cells. Cell suspension containing thrombin was evenly seeded into the micro porous constructs, sealed with fibrinogen, and implanted into immunodeficient mice for 8 weeks. At the end of the 8th week, mouse blood vessels were perfused with radiopaque microfil. The scaffolds were harvested, demineralized and analyzed for neovasculature by microcomputed tomography (micro- CT). The formation of microvasculature was significantly higher in the MSC-HUVEC and MSC-HSC constructs than those seeded with MSC alone or cell-free constructs. Volumetric analysis showed that MSC-HUVEC constructs contained 250% more microvasculature than cell-free construct and 180% more microvasculature than MSC or MSC-HSC constructs. Furthermore, neovascularization in the cell free construct was limited to the surface of the construct. The development of neovascularization from noninvasive sources constitutes an important step in the development of clinical strategies for tissue vascularization of large craniofacial defects.
Temple University--Theses
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Li, Yang. "Blast Performance of Reiforced Concrete Beams Constructed with High-Strength Concrete and High-Strength Reinforcement." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35261.
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This thesis focuses on the dynamic and static behaviour of reinforced concrete beams built using high-strength concrete and high-strength steel reinforcement. As part of this study, a total of 8 high-strength concrete beams, built with and without steel fibres, and reinforced with high strength ASTM A1035 bars are tested under simulated blast loading using the University of Ottawa shock-tube, with an additional 3 companion beams tested under quasi-static loading. The variables considered in this study include: concrete type, fibre content, steel reinforcement ratio and steel reinforcement type. The behaviour of the beams with high-strength steel bars is compared to a companion set of beams reinforced with conventional steel reinforcement. The criteria used to evaluate the blast performance of the beams includes: overall blast capacity, maximum and residual displacements, secondary fragmentation and crack control. The dynamic results show that high strength concrete beams reinforced with high-strength steel are able to resist higher blast loads and reduce displacements when compared to companion beams with conventional steel reinforcement. The results also demonstrate that the addition of steel fibres is effective in controlling crack formation, minimizing secondary blast fragments, reducing displacements and further increasing overall blast capacity. However, the use of high-strength steel and high-strength concrete also shows potential for brittle failures under extreme blast pressures. The static results show that specimens with high-strength steel bars do not increase beam stiffness, but significantly increase peak load carrying capacity when compared to beams with the same ratio of conventional steel reinforcement. The analytical research program aims at predicting the response of the test beams using dynamic inelastic single-degree-of-freedom (SDOF) analysis and includes a sensitivity analysis examining the effect of various modelling parameters on the response predictions. Overall the analytical results demonstrate that SDOF analysis can be used to predict the blast response of beams built with high-strength concrete and steel reinforcement with acceptable accuracy.
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Lapenna, Antonio. "T cells development in vitro : a minimalist approach." Thesis, Cranfield University, 2012. http://dspace.lib.cranfield.ac.uk/handle/1826/7797.
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T lymphocytes are considered an essential and advanced component of the immune system, since these cells are able to discriminate self from non-self, start up an immune reaction and further develop into memory cells. However, therapies based on the use of patient derived newly generated T cells reinoculated into humans do not exist. This is due to difficulties in replicating the peculiar conditions required for T cell development in vitro. The systems developed so far are based on the use of animal or unrelated human thymic tissue and therefore they would not be adequate to be used in any clinical application. Having conjectured that human skin cells, rearranged in a threedimensional fashion, would be able to support the development of human T lymphocytes from hematopoietic stem cells, we developed a model consisting of human skin keratinocytes and fibroblasts arrayed on a synthetic matrix so to create a prototype suitable to be translated into the clinic. In this way we were able to induce few hundred cord blood CD34⁺ haematopoietic stem cells to entirely develop into mature CD4⁺ or CD8⁺ T lymphocytes in vitro. However, circulating adult peripheral CD34⁺ precursors failed to survive in the same conditions. Finally we were able to explain our success as consequence of strong induction of the Notch delta ligand Dll-4 by the keratinocytes cultured in the construct. In synthesis, we report here for the first time that skin keratinocytes, in the presence of fibroblasts and reconfigured in a three-dimensional arrangement, are able to induce the differentiation of a minimal amount of cord but not adult blood stem cells into fully differentiated T cells by acting through the Dll-4 Notch signaling pathway in vitro.
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Liu, Wei. "Rational targeting of Cdc42 in hematopoietic stem cell mobilization and engraftment." University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1303845649.
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Kettern, Nadja [Verfasser]. "Das Hsc/Hsp70 Co-Chaperon-Netzwerk kontrolliert die Antigenaggregation und -präsentation während der Immunzellreifung / Nadja Kettern. Mathematisch-Naturwissenschaftliche Fakultät." Bonn : Universitäts- und Landesbibliothek Bonn, 2011. http://d-nb.info/1016196814/34.
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Sirrs, Christopher. "Health and safety in the British regulatory state, 1961-2001 : the HSC, HSE and the management of occupational risk." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2016. http://researchonline.lshtm.ac.uk/2572268/.
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This thesis engages with recent historical scholarship on occupational health and safety by analysing the conditions that shaped the development of British health and safety regulation between 1961 and 2001. Drawing upon a rich vein of archival material as well as oral history interviews, the thesis focuses on the role played by two regulatory bodies, the Health and Safety Commission (HSC) and Health and Safety Executive (HSE), in generating and enforcing this framework of laws and standards. The thesis illuminates two major historical trends. Firstly, it explores the gradual transformation of the British state in its role as health and safety regulator. Since 1974, the focus of British regulation has been to promote ‘self-regulation’ by employers and employees, and the thesis analyses the ways in which HSC/E has attempted to foster a ‘safety culture’ in British industry, in the context of social, political and economic pressures. Secondly, the thesis analyses the evolution of risk in health and safety regulation, from implicit assumptions and practices in policymaking and enforcement, to the formal demand for all employers to conduct written risk assessments. In so doing, the thesis reconciles various paradoxes. One such paradox is that while the role of the British state in regulating health and safety has ostensibly ‘rolled back’ (e.g. via deregulation), health and safety has in another sense ‘crept forward’, extending beyond the workplace to intervene in public safety and environmental issues. Another paradox is that while British health and safety legislation has been ostensibly ‘successful’ in reducing fatal workplace accidents, it has come under unprecedented public and political scrutiny in recent years. Examining the evolution of health and safety against an extensive theoretical background (e.g. the ‘risk society’), 16 the thesis explains how health and safety has become increasingly central to our work and public lives.
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Swedosh, Philip, and mikewood@deakin edu au. "An Investigation into the skill levels achieved by mathematics students in the V.C.E. and the H.S.C. mathematics courses." Deakin University, 1994. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20051017.153947.
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This study examines whether recent changes to the mathematics courses offered in the final year of secondary school (Year 12) in the state of Victoria, Australia have affected the learning outcomes of students in terms of then: skill levels in algebra, calculus and problem solving; and in terms of their preparation for a tertiary mathematics unit. The impact of these changes on the transition from secondary to tertiary mathematics is also considered.
A comparison is made between students who attempted a first year mathematics unit at the University of Melbourne (U. of M.) having completed the new V.C.E. (Victorian Certificate of Education) mathematics courses and mathematics courses from the previous H.S.C. (Higher School Certificate) system. The comparison involves the use of tests administered upon entrance to a tertiary mathematics unit at the U. of M., and questionnaires.
In 1991, V.C.E, students and H.S.C. students attempted the same mathematics test at the U. of M. and their results were compared. In 1992, the tests were attempted by V.C.E. students only. To compare new V.C.E. students and H.S.C. students, questions on the 1991 test were matched with similar questions on the 1992 tests and a panel of experts determined what the H.S.C. students who attempted the 1991 test would have been expected to average on these matched questions on the 1992 tests had they attempted them. These expected average scores were then compared with the actual scores of the new V.C.E. students. The scores of the groups were scaled when necessary.
Questionnaires were administered to 1991 U. of M, mathematics students who were part of the V.C.E. pilot group in 1990, secondary mathematics educators, tertiary mathematics educators, and 1991 V.C.E. (1992 U. of M.) students.
The mathematical misconceptions exhibited by new V.C.E. students are discussed and their frequencies stated.
The research indicates that the new V.C.E. mathematics courses have provided the V.C.E. mathematics students in this study with significantly lower skill levels and a significantly poorer preparation for a tertiary mathematics unit than those which were previously provided by the H.S.C. mathematics courses.
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Repetylo, Anna H., and n/a. "Factors influencing retention rates in secondary schools within the Wollongong region." University of Canberra. Education, 1993. http://erl.canberra.edu.au./public/adt-AUC20061107.122538.
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Throughout the 1980s, there was a trend in Australia towards increased
participation rates in post-compulsory education. This study examines factors that
influence Year 12 retention rates in four Government secondary schools within the
Wollongong Sub-Region. Factors that were thought to influence students to continue
to Year 12 and sit for the New South Wales Higher School Certificate Examination
included those related to Gender, Socio-economic (relating to occupation of parents,
government financial assistance, and language background), Educational and Career.
The study involved surveying over 400 Year 10 students in four schools by
questionnaires. These schools were chosen for their geographical location and to
include two schools with a history of high retention rates and two schools with low
retention rates.
The questions in the survey were incorporated with a larger survey conducted
in 1989 by the Faculty of Education at the University of Wollongong under the coordination
of Dr. Noeline Kyle ("Everyone expects you to know; A report on careers
advice and industry attitudes towards female students in non-traditional study and
work in the Illawarra", 1990). The questionnaire was piloted in 1988 and after
seeking recommendations from students, teachers and the NSW Department of School
Education Research Group, the survey was administered in 1989.
The study used descriptive research methodology, and Chi-square analysis
was used to establish significance levels in the data.
With regard to gender, the data clearly demonstrated that female students were
more inclined than male students to stay on to Year 12, and have positive reasons for
their decision.
Concerning Socio-Economic factors, the results of this study showed that
students whose parents have a professional background are more likely to stay on to
Year 12. In addition, the achievement of the Higher School Certificate as a preIV
requisite for further study was a strong motivating factor for students staying on to
Year 12. However, students in receipt of Austudy did not appear to relate in a
statistically significant manner with any of the factors that influence the student to stay
on to Year 12. As well, no statistical inference could be drawn from intention to sit for
the HSC and the language most used at home by parents.
With regard to educational factors, the responses from each of the four schools
surveyed showed a high percentage (82 to 85%) of students intending to stay on to
Year 12 and sit for the HSC examination. None of these schools had an appreciably
higher proportion of students intending to sit the HSC exam. However, it was found
that students from one particular school were more likely to undertake further study
and students from this school had a high percentage of both parents with a
professional occupation than any other school.
The findings relating to career factors showed that students who have a
professional career in mind are more likely to proceed to Year 12. It was also found
that students who had school work experience in a professional occupation were more
likely to proceed to Year 12.
The study relates the survey findings to the research literature in Australia, and
also includes a discussion of the limitations of the survey.
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Ulibarri, Roy M. "Habitat Suitability Criteria for Zuni Bluehead Sucker Catostomus discobolus yarrowi and Navajo Nation Genetic Subunit Bluehead Sucker Catostomus discobolus and Comparing Efficiency of AFS Standard Snorkeling Techniques to eDNA Sampling Techniques." Thesis, The University of Arizona, 2016. http://hdl.handle.net/10150/604876.
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I quantified habitat selection for the endangered Zuni Bluehead Sucker Catostomus discobolus yarrowi and the Navajo Nation Genetic Subunit (NNGS) Bluehead Sucker Catostomus discobolus - a recent taxon described from genetic information. Both taxa are found in northern Arizona and New Mexico border regions. I examined fish [≥50 millimeters (mm) total length (TL)] selection of microhabitat conditions (i.e., water velocity, substrate size, overhead cover, water depth, instream cover, and mesohabitat conditions [i.e., pool, run riffle], during summer base flow conditions for NNGS Bluehead Suckers, and during both summer base flow and high spring flow conditions for Zuni Bluehead Suckers in six streams). Electrofishing, seining, and snorkeling were used to evaluate fish occupancy. From this information, I developed stream specific habitat suitability criteria (HSC) and then generalized HSC for each taxon, and tested transferability of the generalized HSC to individual streams. Zuni Bluehead Suckers and NNGS Bluehead Suckers occupied similar habitats: low velocity pools; sand, silt, and pebble substrate; high percent of instream cover; and water temperatures ranging from 2-21°C. However, Zuni Bluehead Suckers selected for low (0-25%) overhead cover where as NNGS Bluehead Sucker selected for high (0-75%) overhead cover. This was likely due to the source of instream cover–aquatic macrophytes that required sunlight in the Zuni Bluehead Sucker streams, and large woody debris falling from overhead branches in the NNGS Bluehead Sucker streams. Suggestions for managers includes maintaining existing cover or artificially construct additional instream cover; promote overhead cover (e.g., maintaining large trees along streams) and pool mesohabitats. In addition to this work I also tested the new method of environmental DNA (eDNA) to further help conservation efforts for these taxa. Environmental DNA has typically been used to detect invasive species in aquatic environments through water samples. I compared the efficacy of eDNA methodology to American Fisheries Society standard snorkeling surveys to detect presence of a rare fish species. My study site included three streams on the Navajo Nation in northern Arizona and northern New Mexico containing Navajo Nation Genetic Subunit Bluehead Sucker Catostomus discobolus and the Zuni Bluehead Sucker Catostomus discobolus yarrowi. To determine sample sites, I first divided entire wetted area of streams into 100-m consecutive reaches. I systematically selected 10 of those reaches for snorkel and eDNA surveys. Water samples were taken in 10-m sections within each 100-m reach, and fish presence via snorkeling was noted in each 10-m section as well. Water samples were collected at the downstream starting point of each reach, and continued upstream in each section 5 to 8 m ahead of the snorkeler. A qPCR was run on each individual water sample in quadruplicate to test for sucker presence or absence. I was able to positively detect both species with eDNA sampling techniques in two out of three streams. Snorkeling resulted in positive detections of both species in all three streams. In streams where fish were detected with eDNA sampling, snorkeling detected fishes at 11-29 sites per stream, where as eDNA detected fish at 3-12 sites per streams. My results suggested that AFS standard snorkeling was more effective at detecting target fish species than eDNA. To improve eDNA sampling, the amount of water collected and tested should be increased. Additionally, filtering water on site may improve eDNA techniques for detecting fish. Future research should focus on standardizing eDNA sampling to provide a widely operational sampling tool similar to electrofishing, netting, and hydroacoustics.
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Zebian, Abir. "Etude du facteur de réparation de l’ADN, Xeroderma pigmentosum du groupe C (XPC), dans les cellules souches hématopoïétiques." Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0223/document.
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Les dommages de l'ADN peuvent s’accumuler dans les cellules souches hématopoïétiques(CSH) suite aux stress externes ou métaboliques et perturber leur fonctionnement et/ou leur maintien.La réparation par excision de nucléotides (NER), initiée par l’arrêt de la transcription (TCR) ou par lareconnaissance de distorsions des régions non transcrites (GGR) de l’ADN, est nécessaire àl’hématopoïèse à long terme. XPC, un facteur clé du système GGR, participe à d’autres réponses austress oxydatif. Le laboratoire a montré que la perte de XPC provoque l’accumulation de mutations, unstress métabolique et la carcinogenèse. Notre objectif est d’évaluer son expression et son rôle dans lemaintien et la différenciation des CSH. Nos résultats montrent qu’il est plus exprimé dans les cellulesimmatures CD34+ que dans les CD34- matures. Aussi, XPC apparaît sous trois poids moléculairesdifférents certainement liés à des modifications post-traductionnelles. Son extinction par ARNinterférence n'affecte ni la prolifération ni la capacité progénitrice in vitro des cellules CD34+.Cependant, les cellules déficientes implantées chez des souris immunodéficientes disparaissentprogressivement suggérant une perte des CSH ou de leur capacité de différenciation. Postulant queles mutations s’accumulent avec le temps, nous avons étudié l’hématopoïèse chez des sourisdéficientes en XPC jeunes et âgées. Les différences décrites dans l’hématopoïèse chez les individusjeunes et âgés sont retrouvées mais, de manière surprenante, aucune différence entre les animauxsauvages et mutés quelque soit l’âge ou le stress génotoxique n’est observée. Les résultats obtenussur les cellules humaines démontrent un rôle potentiel de XPC dans l’hématopoïèse, mais denouvelles investigations sont nécessaires pour mieux comprendre les mécanismes impliqués, et lapossible participation de XPC dans la leucémogenèseDNA damage may accumulate in hematopoietic stem cells (HSC) due to external ormetabolic stresses, leading to perturbation in their function and/or maintenance. Nucleotide excisionrepair (NER), initiated in the DNA by the stop of transcription (TCR) or by the recognition of distortionsin transcribed regions (GGR), is necessary for long-term hematopoiesis. XPC, a key factor in GGR, isimplicated in oxidative stress. The laboratory has demonstrated that XPC loss leads to theaccumulation of mutations, metabolic stress and carcinogenesis. Our objective is to evaluate XPCexpression and its role in HSC maintenance and differentiation. Results showed that XPC is highlyexpressed in immature CD34+ cells compared to mature CD34- cells. In addition, XPC appeared withthree different molecular weights, certainly linked to post-translational modifications. XPC silencing byshRNA did not affect the proliferation or the progenitor ability of CD34+ cells in vitro. However, deficientcells transplanted in immunodeficient mice disappeared progressively, suggesting the loss of HSCs ortheir differentiation capacity. Postulating that mutations accumulate with time, we have studiedhematopoiesis in young and aged XPC deficient mice. Differences described in young and agedhematopoiesis systems were found but, surprisingly, no difference was observed between wild typeand mutant mice at any age or genotoxic stress. Data from human cells demonstrate a potential rolefor XPC in HSC but new investigations are necessary to better understand the mechanisms implicatedand if XPC may participate in leukemogenesis
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Plensa, Nebot Isabel. "Hiperplasia suprarrenal congénita por defecto en la enzima 21-hidroxilasa: caracterización por el sistema HLA y aportación de la biología molecular, La." Doctoral thesis, Universitat de Barcelona, 2003. http://hdl.handle.net/10803/2982.
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La hiperplasia suprarrenal congénita (HSC) comprende un conjunto de trastornos hereditarios de la esteroidogénesis, causados por la deficiencia de alguna de las enzimas necesarias para la conversión del colesterol en cortisol. El más frecuente es el déficit en 21-hidroxilasa, responsable de cerca del 90% de los casos de HSC. El déficit en 21-hidroxilasa es una enfermedad hereditaria autosómica recesiva, causado por una alteración genética en el gen CYP21B que codifica la enzima.Esta enfermedad presenta un espectro muy amplio de manifestaciones clínicas; desde formas severas que se presentan al nacimiento, en las que la virilización puede ir o no acompañada de un síndrome pierde sal, hasta formas más leves en que los signos de virilización se presentan más tardíamente. La incidencia de las formas clásicas de este déficit, oscila alrededor de 1:10.000-15.000 nacimientos, mientras la de las formas no clásicas se ha estimado en 1:1.000 en la población blanca, con marcadas variaciones étnicas.
El objetivo ha sido la caracterización clínica, biológica y genética de la HSC por déficit en 21-hidroxilasa de una población de la Comunitat Autònoma de Catalunya, con el fin de poder realizar un diagnóstico etiológico concluyente y establecer el consejo genético familiar completo.
Han colaborado 53 familias (106 cromosomas no emparentados) con al menos un hijo diagnosticado de HSC por déficit en 21-hidroxilasa, siendo el total de individuos estudiados de 214. De este total, 71 son pacientes que según los síntomas clínicos fueron clasificados en: 13 SW; 5 SV y 53 NC; 102 son progenitores y 41 son hermanos de dichos pacientes, ninguno de ellos clínicamente afecto.
Para la determinación de la función hormonal se practicó una prueba de estimulación con corticotropina (test de ACTH), con valoración de las concentraciones plasmáticas de 17-hidroxiprogesterona antes y tras 30 minutos de la inyección. La determinación de los antígenos de Clase I y Clase II del Sistema HLA, se realizó mediante la técnica de Microlinfocitotoxicidad. El análisis genético consistió en la detección de grandes reordenamientos mediante la técnica de "Southern blot", y la detección de nueve de las mutaciones puntuales más comunes mediante el diseño de una nueva metodología en la que se emplean dos estrategias según la mutación a detectar: ganancia o pérdida de al menos una diana de restricción en el producto de PCR amplificado a partir de DNA genómico o creación de una diana de restricción por amplificación (ACRS-PCR) y posterior digestión con una enzima de restricción apropiada.
El test de ACTH se confirma como fiable, ya que no se observaron falsos positivos ni falsos negativos en los valores obtenidos de 17-hidroxiprogesterona post estimulación. El nomograma de 17-hidroxiprogesterona proporciona un patrón hormonal que facilita, en la mayoría de los casos, el diagnóstico de las distintas formas de presentación clínica del déficit. No se observó la presencia del antígeno HLA-Bw47 en ninguno de los grupos analizados. Las formas no clásicas se encuentran significativamente asociadas al haplotipo HLA-B14-DR1, mientras que las formas clásicas al antígeno HLA-B5(w51).
La metodología utilizada para el análisis molecular del gen ha permitido detectar la mutación causal en el 89,62% de los cromosomas afectos, evaluados globalmente, consolidándose ésta como altamente efectiva en el diagnóstico de esta patología. Las mutaciones más frecuentes observadas han sido: Intrón 2 (50%) en SW; Intrón 2 (50%) y I172N (16,6%) en SV y V281L (61,5%) en NC. El análisis de los pedigrees ha permitido diagnosticar veintiséis formas crípticas y revelar en dos casos la presencia de mutaciones originadas de novo. La concordancia hallada entre el genotipo y el fenotipo ha sido del 97,2%, de ahí, que las predicciones desde el genotipo han de ser hechas todavía con gran cautela.
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Mesquita, Fernanda Cristina de. "Efeito da liraglutida sobre a fibrose hep?tica e c?lulas estreladas ativadas." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2017. http://tede2.pucrs.br/tede2/handle/tede/7593.
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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES
Liver fibrosis is the wound healing response to repeated injury of the liver. This process begins with the damage of the parenchymal cells and subsequent inflammation, characterized by the rupture of the hepatic architecture associated to the increase of the expression of the components of the extracellular matrix. The development of hepatic fibrosis is based on the activation of hepatic stellate cells (HSC) that undergo phenotypic changes and are characterized by loss of vitamin A deposition and increased cell proliferation, triggering hepatic microcirculatory dysfunction and fibrogenesis in patients with chronic liver disease (CLD). Liraglutide is a GLP-1 agonist (glucagon-like peptide 1) well established as an antidiabetic drug, but also has anti-inflammatory properties, in addition to the effectiveness for NAFLD (non-alcoholic fatty liver disease). Therefore, the aim of this study was to evaluate the effects of liraglutide on the HSC phenotype and liver microvascular function using diverse pre-clinical models of CLD. The results obtained demonstrate that Liraglutide de-activated human and rat HSC phenotype through a GLP1-Rindependent mechanism. Liraglutide did not affect the HSC viability but decreased cell proliferation. CLD-rats receiving liraglutide exhibited significantly lower portal pressure (-20%) with a consequent reduction in intrahepatic vascular resistance. There was also a marked improvements in hepatic vascular function, fibrosis, HSC phenotype and sinusoidal endothelial phenotype. The anti-fibrotic effects of liraglutide were confirmed in human liver tissue. In conclusion, this study demonstrates for the first time that liraglutide improves hepatic sinusoidal endothelium in clinically relevant experimental models of cirrhosis, which leads to improvement in fibrosis and portal hypertension, and therefore is valid in the treatment of advanced chronic liver disease.
A fibrose hep?tica ? a resposta cicatricial do f?gado ? les?es repetidas. Este processo inicia com o dano das c?lulas parenquimatosas e consecutiva inflama??o, caracterizado pelo rompimento da arquitetura hep?tica associada ao aumento da express?o dos componentes da matriz extracelular. O desenvolvimento da fibrose hep?tica ? baseado na ativa??o das c?lulas hep?ticas estreladas (HSC) que sofrem mudan?as fenot?picas e se caracterizam pela perda do dep?sito de vitamina A e aumento da prolifera??o celular, desencadeando disfun??o microcirculat?ria hep?tica e fibrog?nese nos pacientes com doen?a hep?tica cr?nica (CLD). A liraglutida ? um an?lago do GLP-1 (glucagon-like peptide 1) bem estabelecido como f?rmaco antidiab?tico, mas que tamb?m possui propriedades antinflamat?rias, al?m da efetividade para NAFLD (doen?a hep?tica gordurosa n?o alco?lica). Por essa raz?o, o objetivo deste estudo foi avaliar os efeitos da liraglutida sobre o fen?tipo das HSC e a fun??o microvascular hep?tica utilizando diversos modelos pr?-cl?nicos de CLD. Os resultados obtidos demonstram que a liraglutida desativou o fen?tipo das HSC humanas e de ratos atrav?s de um mecanismo independente do receptor GLP1. A liraglutida n?o afetou a viabilidade das HSC mas diminuiu a prolifera??o celular. Os ratos com CLD que receberam liraglutida apresentaram press?o portal significativamente menor (-20%) com consequente redu??o da resist?ncia vascular intra-hep?tica. Houve tamb?m uma acentuada melhoria na fun??o vascular hep?tica, fibrose, fen?tipo das HSC e fen?tipo endotelial sinusoidal. Os efeitos anti-fibr?ticos da liraglutida tamb?m foram confirmados em tecido hep?tico humano. Como conclus?o, este estudo demonstra pela primeira vez que a liraglutida melhora o endotelio sinusoidal hep?tico em modelos experimentais clinicamente relevantes de cirrose, o que leva a melhora no quadro fibr?tico e na hipertens?o portal e, portanto, pode ser v?lido no tratamento da doen?a hep?tica cr?nica avan?ada.
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Jayavaradhan, Rajeswari. "Optimization of Gene Editing Approaches for Human Hematopoietic Stem Cells." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1543919940219677.
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Cardoso, Alexandre da Silva Paes. "Predição do comportamento dinâmico de sistemas compostospor eixo-árvore, sistema de fixação e ferramenta de corte de máquinas ferramenta para altas velocidades (HSC)." reponame:Repositório Institucional da UFSC, 2006. https://repositorio.ufsc.br/xmlui/handle/123456789/158353.
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Dissertação (mestrado profissional) - Universidade Federal de Santa Catarina, Centro Tecnológico, Programa de Pós-Graduação em Engenharia Mecânica, Florianópolis, 2006.Made available in DSpace on 2016-01-15T13:56:03Z (GMT). No. of bitstreams: 1 334470.pdf: 4881657 bytes, checksum: 3ec2c638ed7e87d93dceb83ef8632c1f (MD5) Previous issue date: 2006
A predição de condições estáveis de corte é um dos requisitos críticos para a operacionalização da usinagem em altas velocidades. O presente trabalho buscou estudar o comportamento dinâmico de sistemas compostos por eixo-árvore, sistema de fixação e ferramenta de corte de máquinas de usinagem em altas velocidades (HSC), através de medições experimentais e simulações de vibrações por Elementos Finitos, identificando-se os parâmetros modais dos conjuntos, em busca de um maior entendimento dos fenômenos associados à dinâmica do fresamento em altas velocidades. Foram geradas também as cartas de estabilidade dos conjuntos estudados, através de métodos analíticos disponíveis na literatura, para servirem de referência na otimização dos processos de usinagem em altas velocidades.
Abstract : The prediction of steady conditions of cut is one of the critical requirements for the practical implementation of high-speed machining. The present work searched to study the dynamic behavior of systems composites for axle-tree, system of setting and tool of cut of machines of milling in high speed (HSC), through experimental measurements and simulation of vibrations for Finite Elements, identifying the modal parameters of the sets, in search of a bigger agreement of the phenomena associates to the dynamics of milling in high speed. The letters of stability of the studied sets had also been generated, through available analytical methods in literature, to serve of reference in the practical implementation of high-speed machining.
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Souza, Adriano Fagali de. "Contribuições ao fresamento de geometrias complexas aplicando a tecnologia de usinagem com altas velocidades." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/18/18135/tde-14012005-101635/.
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Atualmente, nota-se um crescimento na fabricação de produtos utilizando moldes e matrizes contendo formas geométricas complexas. No entanto, a fabricação destes ferramentais onde se emprega, principalmente, operações de fresamento, não tem acompanhado esta evolução com a mesma velocidade. O advento dos sistemas CAD/CAM, máquinas CNC e da tecnologia de usinagem em altas velocidades (HSC) influenciaram positivamente a fabricação de superfícies complexas. Contudo, nota-se ainda ineficiências neste processo produtivo. A qualidade superficial após as operações de usinagem ainda não é suficiente para que estes ferramentais entrem diretamente na linha de produção. Assim, operações manuais de acabamento são exigidas, elevando o tempo e custo de produção, comprometendo a qualidade dimensional. Com a finalidade de aprimorar a fabricação de moldes e matrizes, este trabalho apresenta uma revisão bibliográfica sobre a usinagem HSC; um estudo sobre a força de usinagem para o fresamento de formas complexas e uma análise sobre a metodologia utilizada por sistemas CAD/CAM e CNC para gerar e interpretar programas NC que contenham movimentações complexas de ferramenta. Análises práticas foram realizadas em um centro de usinagem HSC, e os resultados indicam que as limitações tecnológicas atuais na cadeia CAD/CAM/CNC limitam a usinagem de formas complexas com altas velocidades, reduzindo a velocidade de avanço programada e que as características intrínsecas deste processo de remoção de material demonstrou ser bastante complexo, acarretando em constantes alterações na força de usinagemIn recent years the number of products containing free-form shapes produced by dies and molds have been growing noticeably. However, the milling process used to manufacture those dies and molds does not meet their requirements. The arrival of the CAD/CAM systems and the High Speed Cutting Technology (HSC) helps to improve this manufacturing process. Although to obtain the surface quality needed to meet the dies and molds requirements, a hand finishing still requires. It involves time, money and decrease the product quality. Technological limitations in the CAD/CAM/CNC chain limit the feed rate when milling free-form shape. It also has a negative effect on the surface roughness. Besides, this kind of milling still lacks scientific knowledge of the cutting process. With the aim to support the dies and moulds fabrication, this work presents an overview about HSC Technology; the cutting forces in a non-planar milling; the cutting tool deflection; a detailed description of the process chain involving the CAD/CAM/CNC systems and the methodologies used by those systems to generate and accomplish free-free tool-paths. Free-form milling experiments applying the HSC Technology were made to study the behavior of this process, and the outcomes are presented
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Isaksson, Adam. "Evaluation of Scale-up Model for Flotation with Kristineberg Ore." Thesis, Luleå tekniska universitet, Institutionen för samhällsbyggnad och naturresurser, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-70117.
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The objectives of this project were to survey the flotation circuit of the Boliden concentrator, mass balance collected data and evaluate a scale-up model for laboratory flotation results. The model assumes that half of the recovery to cleaner middlings in a standard laboratory test would report to the final concentrate if it were done in closed circuit, as is the case in a full-scale plant. It has been used by Boliden Mineral AB since 1982 but its accuracy had not been studied since 1986. The model can be categorised as of open circuit type with scale-up factors. The project was based on a complex Ag-Au-Cu-Pb-Zn sulphide ore from the Kristineberg mine. Laboratory tests were done to produce concentrates of CuPb, Cu, Pb and Zn with pulp samples from the concentrator as feed material. The software HSC 9.3 was used to mass balance data from the plant survey. It was decided that the model would be deemed usable if it was able to predict the plant results with the same accuracy as in the survey of 1986. A simulated locked cycle test with split factors (Agar & Kipkie, 1978) was identified as an alternative scale-up model. The results showed that the model was able to predict the plant results with the same accuracy as in 1986. It was especially good at predicting grade and recovery of the main element in a concentrate. For example, it predicted an 18 % higher grade and 11 % lower recovery of Cu to the CuPb concentrate, while a 3 % lower grade and 11 % lower recovery of Zn was predicted to the Zn concentrate. The locked cycle model gave much worse predictions on grades, but more accurate recoveries. It was also better at predicting the behaviour of minor impurity elements such as As and Bi. A recommendation is to combine the two alternatives in a type of "mixed cycle" model. In this study, it would have predicted an 18 % higher grade and 7 % lower recovery of Cu to the CuPb concentrate, as well as a 3 % lower grade and 1 % higher recovery of Zn to the Zn concentrate compared with plant results. Such a model seems to give better figures, but should be put to the test on more samples and ores to confirm this belief. It could at the very least be used to check the reliability of results predicted by the current scale-up model.Syftet med det här examensarbetet var att utföra en detaljprovtagning av flotationskretsen i Bolidens anrikningsverk, massbalansera data och sedan utvärdera en modell för uppskalning av resultat från laboratorieflotationer. Modellen antar att hälften av utbytet till returgodset i ett satsvis laboratorieförsök skulle rapportera till det slutliga koncentratet om det återcirkulerades, såsom i ett anrikningsverk. Den har använts av Boliden Mineral AB sedan 1982 men utvärderades senast 1986. Kategoriskt kan den ses som en uppskalningsmodell av typen öppen krets med skalfaktorer. Projektet baserades på en komplex Ag-Au-Cu-Pb-Zn sulfidmalm från gruvan i Kristineberg. Laboratorieförsök utfördes för att ta fram koncentrat av CuPb, Cu, Pb och Zn, med pulpprover från driften som utgångsmaterial. Programmet HSC 9.3 användes för att massbalansera datan från provtagningen. Det bestämdes att modellen skulle anses som godtagbar ifall den kunde förutspå driftresultatet med samma noggrannhet som 1986. Ett simulerat försök av typen sluten krets (Agar & Kipkie, 1978) identifierades som den mest intressanta alternativmodellen och även den utvärderades. Resultaten visade att modellen än idag ger godtagbara förutsägelser med samma noggrannhet som 1986. Modellen var särskilt bra på att förutspå halt och utbyte av den huvudsakliga metallen till dess eget koncentrat. Den förutspådde exempelvis en 18 % högre halt och 11 % lägre utbyte av Cu till CuPb-koncentratet, samt 3 % lägre halt och 11 % lägre utbyte av Zn till Zn-koncentratet. Den alternativa modellen gav sämre förutsägelser med avseende på halter, men bättre med avseende på utbyten. Den var bättre på att förutspå beteendet hos låghaltiga föroreningar såsom As och Bi. Rekommendationen är att kombinera de två modellerna till en "blandkretsmodell". I den här undersökningen hade ett sådant alternativ förutspått en 18 % högre halt och 7 % lägre utbyte av Cu till CuPb-koncentratet, samt 3 % lägre halt och 1 % högre utbyte av Zn till Zn-koncentratet jämfört med driftresultatet. En sådan modell tycks ge bättre förutsägelser, men bör testas på fler prover och malmtyper. Den borde åtminstone kunna användas för att kontrollera trovärdigheten hos resultaten förutspådda av den nuvarande modellen.
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Fosu, Allen Yushark. "Development of a Chloride Route for Lithium Extraction from Spodumene." Electronic Thesis or Diss., Université de Lorraine, 2023. http://www.theses.fr/2023LORR0094.
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Le lithium est un composant majeur des batteries Li-ion, utilisées dans la fabrication de nombreux appareils électroniques portables. La transition énergétique entraîne le passage des véhicules thermiques aux véhicules électriques et hybrides, qui repose principalement sur l'utilisation de batteries Li-ion pour le stockage réversible de l'énergie. Le développement des véhicules électriques basés sur la technologie lithium-ion est à l'origine d'une demande record de sel de lithium (principalement carbonate et hydroxyde de lithium). Le spodumène est la principale source de lithium à partir de minerais. Son traitement nécessite une transformation de phase de la forme α à la forme β, suivie d'un grillage conduisant à la formation d'un sel de lithium après des étapes de lixiviation, de purification et de récupération. Dans cette thèse, le concentré de spodumène de la région de Pilbara en Australie occidentale a été caractérisé pour le traitement thermique et hydrométallurgique. Le traitement thermique est responsable de la formation de fissures dans les grains qui deviennent plus visibles avec l'augmentation de la température. La désintégration du matériau, la fusion et l'agglomération avec les minéraux contenus dans la gangue ont également été observées en augmentant la température jusqu'à 1050 °C. Des énergies d'activation apparentes de 655±20 kJ mol-1 ont été calculées pour la transformation de l'α-spodumène, ce qui confirme une forte dépendance à la température pour les transformations polymorphes du spodumène. Par la suite, nous avons étudié une voie alternative aux méthodes conventionnelles (procédé à l'acide sulfurique) pour traiter le concentré de spodumène dans le but de réduire la consommation d'énergie élevée des étapes de transformation de phase et de grillage au sulfate. Pour ce faire, nous avons procédé à la chloration directe de l'α-spodumène avec du chlorure de calcium, suivie d'une lixiviation à l'eau du résidu pour récupérer le chlorure de lithium. L'analyse du résidu obtenu après lixiviation a indiqué que la forme α était le seul polymorphe présent, ce qui suggère que l'extraction se fait directement à partir de la phase α. Dans des conditions optimales, un traitement thermique à 1000 °C pendant 60 minutes du concentré de spodumène en présence de chlorure de calcium à un rapport molaire chlorure de calcium/spodumène de 2,0 est nécessaire pour extraire près de 90 % du lithium et récupérer 85 % dans la liqueur de lixiviation. Une énergie d'activation apparente d'environ 122±6 kJ mol-1 a été calculée pour des températures allant de 800 à 950 ℃. La liqueur obtenue après lixiviation a été purifiée par échange d'ions et extraction par solvant afin de récupérer du chlorure de lithium d'une pureté suffisante pour être considéré comme un précurseur dans la production de matériaux pour batteries au lithium-ionLithium is a major component of Li-ion batteries, used in the manufacture of many portable electronic devices. The energy transition is driving the shift from thermal to electric and hybrid vehicles, which relies mainly on the use of Li-ion batteries for reversible energy storage. The development of electric vehicles based on lithium-ion technology is responsible for a record demand for lithium salt (mainly lithium carbonate and hydroxide). Spodumene is the main source of lithium from ores. Its processing requires a phase transformation from α-form to β-form, followed by roasting leading to the formation of a lithium salt after a leaching, purification, and recovery steps. In this thesis, spodumene concentrate from the Pilbara region of Western Australia was characterized for thermal and hydrometallurgical processing. Heat treatment is responsible for the formation of cracks in the grains which become more noticeable with increasing temperature. Disintegration of the material, melting and agglomeration with minerals contained in the gangue have also been observed by increasing the temperature up to 1050 °C. Apparent activation energies of 655±20 kJ mol-1 was calculated for the transformation of α-spodumene which confirms a strong temperature dependence for polymorphic transformations of spodumene. Subsequently, we investigated an alternative route to conventional methods (sulphuric acid process) to treat the spodumene concentrate with the aim of reducing the high energy consumption of the phase transformation and sulphate roasting steps. This was achieved by direct chlorination of α-spodumene with calcium chloride, followed by water leaching of the residue to recover lithium chloride. Analysis of the residue obtained after leaching indicated that the α-form was the only polymorph present, suggesting that extraction occurs directly from the α-phase. Under optimal conditions, heat treatment at 1000 °C for 60 minutes of the spodumene concentrate in the presence of calcium chloride at a calcium chloride/spodumene molar ratio of 2.0 is required to extract nearly 90% of lithium and recover 85% in the leach liquor. An apparent activation energy of about 122±6 kJ mol-1 was calculated for temperatures ranging from 800 to 950 ℃. The liquor obtained after leaching was purified by ion exchange and solvent extraction to recover lithium chloride of sufficient purity for consideration as a precursor in the production of lithium-ion battery materials