322 research outputs found

    Structure determination of thin polymer films using GIXRd and AFM

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    Structure determination of thin polymer films using GIXRD and AFM Both atomic force microscopy (AFM) and grazing incidence x-ray diffraction (GIXRD) are used to determine the structure of polymer thin films. To enable experiments using these techniques to be conducted experimental apparatus was designed and built. These apparatus' included an in-situ heater to allow investigations at elevated temperatures to be conducted as well as a chamber for the work conducted using GIXRD to minimise the background scattering incident on the detector. The structure of two polymers, F8 and PQT-12, have been investigated using GIXRD. Both of these polymers align in a layered geometry normal to the surface, and in an isotropic polycrystalline ordering in the plane of the surface. The F8 polymer, while in the a-crystalline phase, has a unit cell dimension of 27.3 0.3A normal to the surface and unit cell dimensions of 24.3 0.3A and 17.1 0.2A in the plane of the surface. As- spun PQT-12 of molecular weight of 5000amu has been found to form a metastable self- assembled crystalline phase with unit cell dimensions of 35.6 0.7A out-of-plane and 13.10 0.12A, 16.4 0.6A in-plane. The structure of PQT-12 has been shown to be dependent on molecular weight, annealing and physical preparation of the substrate. The rate and mechanisms of crystallisation of a third polymer, PET, have also been investigated as a function of anneal temperature. The crystallisation was followed at each given temperature to follow the growth of individual spherulites. As the thickness of the PET film was increased from 43nm to 120 nm the radial growth rate of the spherulites increased linearly from 8.0 0.9nm/min to 14.3 1.3nm/min.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

    Effects of progesterone on mammary carcinogenesis by DMBA applied directly to rat mammae.

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    The effects and site(s) of action of progesterone on DMBA mammary carcinogenesis in the rat, when a small dose of the carcinogen was applied directly to the inguinal mammary gland, were investigated. No reduction in tumour yield was apparent when progesterone was administered s.c. for 18 days before dusting DMBA. This finding contrasts with a previously reported inhibitory effect on carcinogenesis when hormone treatment was followed by intragastric administration of DMBA. When progesterone injections were begun either 2 days before or 2 days after direct application of DMBA, and were continued until the end of the experiment (135 or 195 days) an enhancement in carcinogenesis was observed similar to that previously demonstrated after gastric intubation of DMBA. These findings, together with previously reported observations, suggest that progesterone may exert its inhibitory effect on carcinogenesis by acting at a site outside the breast, perhaps on the liver. However, it is likely that the hormone acts directly on the mammary tissue to exert its enhancing effect on tumorigenesis

    C55-groups

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    We classify the C55-groups, i.e., ïŹnite groups in which the centralizer of every 5-element is a 5-group

    Influence de la puissance de l'entrée sur la capacité de poursuite des filtres adaptatifs

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    Une analyse de l'influence de la puissance de l'entrée sur la capacité de poursuite de l'algorithme du gradient stochastique (GS) est présentée. Cet algorithme est utilisé en identification d'un systÚme non stationnaire dont les variations sont modélisées par une promenade aléatoire. Nous montrons l'influence contradictoire de la puissance de l'entrée sur la déviation quadratique moyenne et l'erreur quadratique moyenne résiduelle optimales. Lorsque deux non stationnarités sont combinées, celle de l'entrée du systÚme à identifier et celle du systÚme, nous montrons l'apport relatif de certains algorithmes normalisés pour une identification robuste face aux variations de la puissance de l'entrée

    Ultra-deep sequencing reveals dynamics of drug Resistance-Associated variants in Hepatitis C viruses: Relevance to treatment outcome and resistance screening

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    Hepatitis C is a global health issue with approximately 3% of the worlds’ population estimated to be infected with the hepatitis C virus (HCV) Inefficiencies in treatment has led to development of direct-acting antivirals (DAAs) that specifically target HCV proteins involved in the virus’s lifecycle1. One of the major concerns arising from the use of the DAAs is the emergence of resistance-associated variants (RAVs) that affect the efficacy of the drugs. RAVs are generally associated with a fitness cost and the use of ultra-deep pyrosequencing technology has shown that in most treatment naïve subjects low frequency circulating strains carry RAVs2. The aim of the study was to investigate i) the clinical relevance of low frequency RAVs; ii) the persistence of RAVs and iii) compensatory mutations in a subset of subjects who had failed boceprevir (SCH503034; protease inhibitor)

    The Binding Site for TRAF2 and TRAF3 but Not for TRAF6 Is Essential for CD40-Mediated Immunoglobulin Class Switching

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    AbstractTo define the role of TRAF proteins in CD40-dependent isotype switching in B cells, we introduced wild-type (WT) and mutant CD40 transgenes that lacked the binding motifs for TRAF6 (CD40ΔTRAF6), TRAF2 and TRAF3 (CD40ΔTRAF2/3), or both (CD40ΔTRAFs) into B cells of CD40−/− mice. The in vivo isotype switch defect in CD40−/− mice was fully corrected by WT and CD40ΔTRAF6, partially by CD40ΔTRAF2/3, and not at all by CD40ΔTRAFs transgenes. CD40-mediated isotype switching, proliferation, and activation of p38, JNK, and NFÎșB in B cells were normal in WT and CD40ΔTRAF6 mice, severely impaired in CD40ΔTRAF2/3, and absent in CD40ΔTRAFs mice. These results suggest that binding to TRAF2 and/or TRAF3 but not TRAF6 is essential for CD40 isotype switching and activation in B cells

    TACI and BAFF-R mediate isotype switching in B cells

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    The tumor necrosis factor family members BAFF and APRIL induce Ig isotype switching in human B cells. We analyzed the ability of BAFF and APRIL to induce isotype switching in murine B cells to IgG1, IgA, and IgE. APRIL and BAFF each engage two receptors, transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI) and B cell maturation antigen (BCMA), on B cells. In addition, BAFF engages a third receptor on B cells, BAFF-R. To determine the role of these receptors in isotype switching, we examined B cells from mice deficient in TACI, BCMA, and BAFF-R. The results obtained indicate that both TACI and BAFF-R are able to transduce signals that result in isotype switching

    Venture capital on a shoestring: Bioventures’ pioneering life sciences fund in South Africa

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    <p>Abstract</p> <p>Background</p> <p>Since 2000, R&D financing for global health has increased significantly, with innovative proposals for further increases. However, although venture capital (VC) funding has fostered life sciences businesses across the developed world, its application in the developing world and particularly in Africa is relatively new. Is VC feasible in the African context, to foster the development and application of local health innovation?</p> <p>As the most industrially advanced African nation, South Africa serves as a test case for life sciences venture funding. This paper analyzes Bioventures, the first VC company focused on life sciences investment in sub-Saharan Africa. The case study method was used to analyze the formation, operation, and investment support of Bioventures, and to suggest lessons for future health venture funds in Africa that aim to develop health-oriented innovations.</p> <p>Discussion</p> <p>The modest financial success of Bioventures in challenging circumstances has demonstrated a proof of concept that life sciences VC can work in the region. Beyond providing funds, support given to investees included board participation, contacts, and strategic services. Bioventures had to be proactive in finding and supporting good health R&D.</p> <p>Due to the fund’s small size, overhead and management expenses were tightly constrained. Bioventures was at times unable to make follow-on investments, being forced instead to give up equity to raise additional capital, and to sell health investments earlier than might have been optimal. With the benefit of hindsight, the CFO of Bioventures felt that partnering with a larger fund might benefit similar future funds. Being better linked to market intelligence and other entrepreneurial investors was also seen as an unmet need.</p> <p>Summary</p> <p>BioVentures has learned lessons about how the traditional VC model might evolve to tackle health challenges facing Africa, including how to raise funds and educate investors; how to select, value, and support investments; and how to understand the balance between financial and social returns. The experience of the fund suggests that future health funds targeting ailments of the poor might require investors that accept health benefits as part of their overall “return.” Learning from Bioventures may help develop health innovation funding for sub-Saharan African that has combined health, financial, and economic development impacts.</p

    HIV-1 Populations in Semen Arise through Multiple Mechanisms

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    HIV-1 is present in anatomical compartments and bodily fluids. Most transmissions occur through sexual acts, making virus in semen the proximal source in male donors. We find three distinct relationships in comparing viral RNA populations between blood and semen in men with chronic HIV-1 infection, and we propose that the viral populations in semen arise by multiple mechanisms including: direct import of virus, oligoclonal amplification within the seminal tract, or compartmentalization. In addition, we find significant enrichment of six out of nineteen cytokines and chemokines in semen of both HIV-infected and uninfected men, and another seven further enriched in infected individuals. The enrichment of cytokines involved in innate immunity in the seminal tract, complemented with chemokines in infected men, creates an environment conducive to T cell activation and viral replication. These studies define different relationships between virus in blood and semen that can significantly alter the composition of the viral population at the source that is most proximal to the transmitted virus
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