Le sang provenant d’un cordon ombilical (SCO) représente une bonne source de cellules souches hématopoïétiques (CSH) pour des transplantations. Cependant, le nombre de cellules souches contenues dans ce sang est souvent insuffisant pour greffer un adulte. Le mécanisme intervenant dans la domiciliation de ces cellules au sein de la moelle osseuse (MO) est encore mal compris. On sait que l’interaction entre la chimiokine SDF-1 et le récepteur CXCR4, présent sur les cellules CD34+ de SCO, mène à la migration de ces cellules en direction de la MO. Nous pensons que l’augmentation de la proportion de cellules qui réussit à se greffer pourra pallier au problème du nombre. Les produits de dégradation, C3a et le C3desarg,, issus du système du complément, sont connus pour favoriser la réponse de cellules exprimant CXCR4 vers SDF-1. Nous avons analysé l’effet du C3adesarg, molécule non anaphylatoxique, sur la migration cellulaire vers SDF-1, de même que sur la prise de greffe des cellules CD34+ issues de SCO suite à une transplantation sur des souris NOD/SCIDyC-. Nos expériences ont démontré que le C3a ainsi que le C3adesarg augmentaient tous les deux la réponse des cellules CD34+ vers SDF-1. Toutefois, nous n’avons pas pu démontrer que ces molécules liaient directement le récepteur CXCR4. Par contre, le composé C3adesarg favorise la prise de greffe des cellules CD34+ de SCO. Il serait donc un bon candidat pour poursuivre une optimisation de ses propriétés. Nous avons également constaté que suite à une transplantation chez la souris, les cellules CD34+ de SCO subissent une hausse d’expression transitoire de leur CXCR4 environ quatre jours après la greffe. Cette hausse d’expression coïncide avec la multiplication des cellules CD34+ dans la MO. Nous avons également confirmé qu’une cellule CD34+ avec une forte expression de CXCR4 était dans un état prolifératif. Nos données suggèrent que l’interaction directe avec les cellules stromales soit responsable de cette hausse d’expression de CXCR4. / Since the first successful cord blood (CB) transplant was performed there has been a gradual increase in the use of CB for haematopoietic stem cell (HSC) transplantation, but the number of stem cells per CB is in general too low to ensure successful transplantation in adult patients. We would like to bypass the limitation of insufficient number of these cells in CB by enhancing the engraftment efficiency. The chemokine stromal-derived factor (SDF)-1, that binds to its receptor, CXCR4, plays an important and unique role in regulating the trafficking of HSC and their homing/retention in bone marrow (BM), but molecular regulatory mechanism of niches for HSC maintenance remains unclear. The complement C3 cleavage fragments, C3a and C3adesarg, modulate the responsiveness of CXCR4-expressing cell lines to SDF-1. We assessed the effect of the non anaphylatoxic complement fragment, C3adesarg, on SDF-1 responsiveness and engraftment of CB-HSC transplantation in a NOD/SCIDyC- mouse model. Complement breakdown products C3a and C3adesarg both increase the responsiveness of CD34+ cells to SDF-1. We find no evidence for direct interaction of complement fragments with CXCR4. Our data suggest that C3adesarg might contribute to optimize CB-HSC homing to bone marrow, and therefore efficacy of cord blood transplantation. We quantified the number of CXCR4 on the surface of CB-CD34+ after transplantation in mice. Our results showed that there is a transient overexpression of CXCR4 on the surface of HSC CD34+ found in the BM of NOD/SCIDyC- mice after 4-5 days post-injection. This transient overexpression correlated with multiplication of CD34+ cells in the BM. We confirm that the cells with an overexpression of CXCR4 are in a proliferation state. Our data suggested that this transient overexpression is caused by an interaction with the stomal cells.

No description available.

Abstract This dissertation studies the impact of heterogeneous wireless networks on the design and implementation of mobile video streaming services. The aim is to enable Quality of Service (QoS) sensitive video streaming services to take full advantage of the access diversity of heterogeneous networks in order to optimize their operation in terms of quality and efficiency of network resource usage. This nevertheless requires support beyond the layered communication architecture of today’s Internet. The thesis proposes an architecture for end-to-end cross-layer signaling and control for video streaming systems. The architecture supports extensive context informa- tion transfer in heterogeneous networks; thus, enabling the efficient management of video stream adaptation and user terminal mobility in a diverse and dynamic network environment. This thesis also studies and proposes cross-layer enhancements for adaptive video streaming and mobility management functions enabled by the cross- layer architecture. These include cross-layer video adaptation, congestion-triggered handovers, and concurrent utilization of multiple access networks in the video stream transport. For the video adaptation and multipath transmission, the flexible adaptation and transmission capabilities of the novel scalable video coding technology are used. Regarding the mobility management, the proposed solutions essentially enhance the handover decision-making of the Mobile IP protocol to better support QoS-sensitive video streaming. Finally, the thesis takes a holistic view on the application adaptation and mobility management, and proposes a solution for coordinated control of these two operations in order to achieve end-to-end optimization. The resulting mobile video streaming system architecture and the cross-layer control algorithms are evaluated using network simulations and real prototypes. Based on the results, the proposed mechanisms can be seen to be viable solutions for improving video streaming performance in heterogeneous wireless networks. They require changes in the communication end-points and the access network but support gradual deployment. This allows service providers and operators to select only a subset of the proposed mechanisms for implementation. The results also support the need for cross-layer signaling and control in facilitating efficient management and utilization of heterogeneous wireless networks. / Tiivistelmä Väitöskirja tutkii langattomien ja heterogeenisen verkkoympäristöjen vaikutusta erityisesti mobiilikäyttöön suunnattuihin suoratoistovideopalveluihin (streaming). Työn tavoitteena on löytää keino optimoida verkkoyhteyden palvelunlaadulle (QoS) herkän suoratoistovideon toiminta sekä videopalvelun laadun että verkon tiedonsiirtokapasiteetin käytön osalta. Tämä tapahtuu mahdollistamalla heterogeenisten verkkojen tehokas käyttö suoratoistovideopalvelujen tapauksessa. Tavoitellut parannukset vaativat kuitenkin muutoksia nykyiseen kerroksittaiseen Internet-arkkitehtuuriin. Väitöskirjassa esitetään arkkitehtuuri protokollakerrosten välisen tiedon (cross-layer) välitykseen ja hyödyntämiseen suoratoistovideopalvelujen tiedonsiirron kontrolloinnissa. Arkkitehtuuria voidaan käyttää laaja-alaiseen kontekstitiedon välitykseen tietoverkoissa, mikä mahdollistaa tehokkaan videopalvelun adaptoinnin ja päätelaitteen liikkuvuudenhallinnan heterogeenisissa verkoissa, joissa palvelunlaatu vaihtelee. Väitöskirja myös ehdottaa erilaisia ratkaisuja videopalvelun adaptoinnin ja tiedonsiirron parantamiseksi arkkitehtuuria hyödyntämällä. Näihin lukeutuvat usealle protokollakerrokselle toteutettu videon adaptointi, verkkoyhteyden ruuhkautumiseen reagoiva yhteydensiirto sekä usean verkkoyhteyden samanaikainen käyttö videopalvelun tiedonsiirrossa. Videon adaptoinnissa ja siirrossa hyödynnetään uutta skaalautuvaa videonkoodausteknologiaa, joka mahdollistaa vaaditun, joustavan videobittivirran muokkauksen. Liikkuvuudenhallinnan osalta työssä keskitytään pääosin kehittämään Mobile IP -protokollan päätöksentekoa suoratoistovideopalvelujen tapauksessa. Lopuksi väitöskirjassa esitetään kokonaisvaltainen ja koordinoitu ratkaisu videopalvelun adaptoinnin sekä päätelaitteen liikkuvuuden hallintaan päästä päähän -optimoinnin saavuttamiseksi. Tuloksena esitetyt järjestelmäarkkitehtuuri ja protokollakerrosten välistä tietoa käyttävät hallinta-algoritmit evaluoitiin simulaatioiden ja oikeiden prototyyppien avulla. Tulokset osoittavat, että ehdotettuja menetelmiä voidaan käyttää parantamaan suoratoistovideopalvelujen suorituskykyä heterogeenisissa verkoissa. Ratkaisut vaativat muutoksia verkko- ja palveluarkkitehtuureihin, mutta niiden asteittainen tai osittainen käyttöönotto on mahdollista. Tulokset osoittavat myös protokollakerrosten välisen tiedon tarpeellisuuden langattomien ja heterogeenisten verkkojen tehokkaassa käytössä.

For positioning of linear stages in absolute coordinates, there is a general need to find a reference position since the initial one is unknown. This is commonly called homing. To reduce costs and facilitate assembly, homing can be performed without additional sensors, known as sensorless homing. This thesis delves into sensorless homing, specifically with respect to stepper motors, and develops a graphical application for control of them. The commercial technology StallGuard is applied inconjunction with exploration into how it – and sensorless load detectionin general – functions. The resulting graphical application can be used to configure the stepper motors, perform homing using StallGuard, and automatically tune StallGuard to work despite varying conditions. In addition, rudimentary sensorless load detection independent from StallGuard is developed, demonstrating how it could work in practice. Testing shows homing with StallGuard resulting in a position within a ±5μm window in 94% of cases, less than 1/7 the width of an average strand of human hair. Additionally, homing is easily performed with a single button press from the graphical interface, with optional additional configuration available.

This interdisciplinary thesis explores the foodways of six Syrian migrant families, both immigrants and refugees, in California and the role that culinary customs play in their homing process. The homing process is the dynamic way in which people create home according to their life circumstances: food, eating, and culinary customs after migration in this case. Home is not only the place where people live, but also, where they come from and how they feel comfortable; home is both a physical space and an abstract concept. Home, and the various definitions of home, are mapped out in this project because understanding these various meanings allows for a clear understanding of the homing process for migrants. To explore Syrian migrants’ foodways in California, I conducted interviews with these six families, and, in analyzing the interviews, chose four salient culinary customs to demonstrate the role of foodways in the homing process. The four culinary customs are: the distinct morning coffee ritual; mealtimes and meal routines imposed by work or school; lunch as the day’s main meal, which must be tabekh (cooked food); and the importance of handmade food. Taken together, the consistent patterns followed, and energy devoted towards food and culinary customs provide evidence that effort expended in maintaining customary foodways is effort in recreating home. This project adds to existing scholarship on the relationship between foodways and migrant communities’ identity maintenance in that it demonstrates a unique and particular devotion to the rhythm and ritual of foodways that allows Syrians to not only make a new home, but to also feel at home in a new land.

Indiana University-Purdue University Indianapolis (IUPUI) / Adult hematopoietic stem cells (HSC) are routinely used to reconstitute hematopoiesis after myeloablation; however, transplantation efficacy and multilineage reconstitution can be limited by inadequate HSC number, or poor homing, engraftment or self-renewal. We have demonstrated that mouse and human HSC express prostaglandin E2 (PGE2) receptors, and that short-term ex vivo exposure of HSC to PGE2 enhances their homing, survival and proliferation, resulting in increased long-term repopulating cell and competitive repopulating unit (CRU) frequency. HSC pulsed with PGE2 are more competitive, as determined by head-to-head comparison in a competitive transplantation model. Enhanced HSC frequency and competitive advantage is stable and maintained upon multiple serial transplantations, with full multi-lineage reconstitution. PGE2 increases HSC CXCR4 mRNA and surface expression and enhances their migration to SDF-1α in vitro and homing to bone marrow in vivo and stimulates HSC entry into and progression through cell cycle. In addition, PGE2 enhances HSC survival, associated with an increase in Survivin mRNA and protein expression and reduction in intracellular active caspase-3. While PGE2 pulse of HSC promotes HSC self-renewal, blockade of PGE2 biosynthesis with non-steroidal anti-inflammatory drugs (NSAIDs) results in expansion of bone marrow hematopoietic progenitor cells (HPC). We co-administered NSAIDs along with the mobilizing agent granulocyte-colony stimulating factor (G-CSF) and evaluations of limiting dilution transplants, assays monitoring neutrophil and platelet recoveries, and secondary transplantations, clearly indicate that NSAIDs facilitate mobilization of a hematopoietic graft with superior functional activity compared to the graft mobilized by G-CSF alone. Enhanced mobilization has also been confirmed in baboons mobilized with G-CSF and a NSAID. Increases in mobilization are the result of a reduction of signaling through the PGE2 receptor EP4, which results in marrow expansion and reduction in the osteoblastic HSC niche. We also identify a new role for cannabinoids, an eicosanoid with opposing functions to PGE2, in hematopoietic mobilization. Additionally, we demonstrate increased survival in lethally irradiated mice treated with PGE2, NSAIDs, or the hypoxia mimetic cobalt chloride. Our results define novel mechanisms of action whereby eicosanoids regulate HSC and HPC function, and characterize novel translational strategies for hematopoietic therapies.

No description available.

No description available.

OBJECTIVES: The integrin α4β7 is the gut-homing receptor for lymphocytes. It also is an important co-receptor for human immunodeficiency virus (HIV) via glycoprotein (gp)120 binding. Depletion of gut cluster of differentiation (CD)4 T cells is linked to chronic inflammation in patients with HIV; however, measuring CD4 cells in the gut is invasive and not routine. As such, establishing a peripheral marker for CD4 depletion of the gut is needed. We hypothesized that α4β7 CD4 T cells are depleted in the peripheral blood of treatment-naïve patients with HIV compared with healthy controls. METHODS: The study groups were treatment-naïve patients with HIV and uninfected controls. Subjects were included if they were 18 years or older with no history of opportunistic infections, active tuberculosis, or cancer. We collected peripheral blood and examined on whole blood using flow cytometry for the following cell surface markers: CD4, CD45RO, chemokine receptor type 5, C-X-C chemokine receptor type 4 (CXCR4), and the integrin β7. We collected demographic information, including age, sex, and ethnicity, as well as viral load (VL) and CD4 count. Two-samplettests and Fisher exact tests were used to compare the differences between the two groups. Spearman correlation coefficients were calculated between CD4 count and log10-VL and percentage of CD4+/CD45RO+/β7+and log10-VL in patients. RESULTS: Twenty-two subjects were enrolled in the study (12 patients with HIV and 10 controls). There were no differences in age or sex between the two groups. There were more Hispanics and fewer Asians in the group comprising patients with HIV compared with the control group (7 vs 2 and 0 vs 4,P= 0.05, respectively). Patients infected with HIV had significantly lower frequencies of CD4+/CD45RO+/β7+cells (median 12%, range 5-18 compared with uninfected controls: median 20%, range 11-26,P= 0.0007). There was a statistically significant difference in the percentage of CD4+/CD45RO+/C-X-C chemokine receptor type 4+cells between patients (72%, range 60%-91%) compared with controls (79%, range 72%-94%,P= 0.04). The percentage of CD4+/CD45RO+/chemokine receptor type 5+did not differ between the group of patients with HIV and the control groups (22%, range 11%-57% vs 27%, range 14%-31%;P= 0.8, respectively). There was no correlation between percentage of CD4+/CD45RO+/β+cells and log10-VL as measured by the Spearman correlation coefficient (r= 0.05,P= 0.88) in patients infected with HIV. CONCLUSIONS: Memory CD4 β7+cells are reduced significantly in the peripheral blood of untreated patients infected with HIV, which could be used as a noninvasive indicator of intestinal CD4 T cell loss and recovery. Further studies are needed to examine whether depletion of these CD4+/CD45RO+/β7+cells in the peripheral blood parallels depletion in the gut of treatment-naïve patients with HIV and whether levels return to control levels after treatment.

Ophiostoma novo-ulmi is the causal agent of Dutch elm disease (DED) which has had a severe impact on the urban landscape in Canada. This research program focused on developing molecular genetic strategies to control this pathogenic fungus. The first strategy involved the development of RNA interference (RNAi) for the down-regulation of genes involved in pathogenicity. An efficient RNAi cassette was developed to suppress the expression of the endopolygalacturonase (epg1) locus which encodes a cell-wall degrading enzyme. This epg1-RNAi cassette significantly reduced the amount of polygalacturonase activity in the fungus and resulted in almost complete degradation of epg1 mRNA. The need for a native promoter to selectively down-regulate specific gene loci was addressed by developing a carbon-catabolite regulated promoter (alcA) to drive the expression of the epg1-RNAi cassette. The expression of an alcA-driven epg1-RNAi cassette resulted in the down-regulation of epg expression under glucose starvation but normal levels of expression in high glucose. The expression could therefore be controlled by culture conditions. The second strategy explored the potential of using dsRNA viruses to vector disruptive RNAi cassettes. An isolate of O. novo-ulmi strain 93-1224 collected in the city of Winnipeg, was infected by two dsRNA mitoviruses which upon sequence characterization were named OnuMV1c and OnuMV7. To assess the transmissibility of this dsRNA virus the infected isolate 93-1224 was paired with three naive isolates of the related fungi O. ulmi and O. himal-ulmi. Through the use of nuclear and mitochondrial markers it was determined that the virus OnuMV1c may not rely on mitochondrial fusion for transmission but may have a cytoplasmic transmission route. This investigation of gene expression and manipulation has provided tools to help understand gene regulation in O. novo-ulmi. It has also added to our knowledge of mitoviruses, their transmission and potential use as a biological control. By enhancing our understanding of transmissible hypovirulence this work contributes to efforts to develop a new approach to target DED as well as a potential model for the control of other fungal diseases. / Graduate / 0307 / 0306 / 0369 / jscarneiro@hotmail.com