4,454 research outputs found

    Dual Acting Polymeric Nano-Aggregates for Liver Cancer Therapy

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    Liver cancer treatments are often hindered by poor drug physicochemical properties, hence there is a need for improvement in order to increase patient survival and outlook. Combination therapies have been studied in order to evaluate whether increased overall efficacy can be achieved. This study reports the combined treatment of liver cancer cells with a combination treatment of chemotherapeutic agent paclitaxel and pro-apoptotic protein cytochrome C. In order to administer both agents in a single formulation, a poly(allylamine)-based amphiphile has been fabricated with the incorporation of a hybrid iron oxide-gold nanoparticle into its structure. Here, the insoluble paclitaxel becomes incorporated into the hydrophobic core of the self-assemblies formed in an aqueous environment (256 nm), while the cytochrome C attaches irreversibly onto the hybrid nanoparticle surface via gold-thiol dative covalent binding. The self-assemblies were capable of solubilising up to 0.698 mg/mL of paclitaxel (700-fold improvement) with 0.012 mg/mL of cytochrome C also attached onto the hybrid iron oxide-gold nanoparticles (HNPs) within the hydrophobic core. The formulation was tested on a panel of liver cancer cells and cytotoxicity was measured. The findings suggested that indeed a significant improvement in combined therapy (33-fold) was observed when compared with free drug, which was double the enhancement observed after polymer encapsulation without the cytochrome C in hepatocellular carcinoma (Huh-7D12) cells. Most excitingly, the polymeric nanoparticles did result in improved cellular toxicity in human endothelian liver cancer (SK-hep1) cells, which proved completely resistant to the free drug

    NASA's Astronant Family Support Office

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    During the NASAMir program of the 1990s and due to the challenges inherent in the International Space Station training schedule and operations tempo, it was clear that a special focus on supporting families was a key to overall mission success for the ISS crewmembers pre, in and postflight. To that end, in January 2001 the first Family Services Coordinator was hired by the Behavioral Health and Performance group at NASA JSC and matrixed from Medical Operations into the Astronaut Office's organization. The initial roles and responsibilities were driven by critical needs, including facilitating family communication during training deployments, providing missionspecific and other relevant trainings for spouses, serving as liaison for families with NASA organizations such as Medical Operations, NASA management and the Astronaut Office, and providing assistance to ensure success of an Astronaut Spouses Group. The role of the Family Support Office (FSO) has modified as the ISS Program matured and the needs of families changed. The FSO is currently an integral part of the Astronaut Office's ISS Operations Branch. It still serves the critical function of providing information to families, as well as being the primary contact for US and international partner families with resources at JSC. Since crews launch and return on Russian vehicles, the FSO has the added responsibility for coordinating with Flight Crew Operations, the families, and their guests for Soyuz launches, landings, and Direct Return to Houston postflight. This presentation will provide a summary of the family support services provided for astronauts, and how they have changed with the Program and families the FSO serves. Considerations for future FSO services will be discussed briefly as NASA proposes one year missions and beyond ISS missions. Learning Objective: 1) Obtain an understanding of the reasons a Family Support Office was important for NASA. 2) Become familiar with the services provided for astronauts and their families and how they changed with the Program and family needs

    Changes in expression and activity of the secretory pathway Ca2+ATPase 1 (SPCA1) in A7r5 vascular smooth muscle cells cultured at different glucose concentrations

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    Diabetes mellitus-related vascular disease is often associated with both a dysregulation of Ca2+^{2+} homoeostasis and enhanced secretory activity in VSMCs (vascular smooth muscle cells). Here, we employ a commonly used rat cell line for VSMCs (A7r5 cells) to investigate the effects of glucose on the expression and activity of the SPCA1 (secretory pathway Ca2+^{2+}-ATPase 1; also known as ATP2C1), which is a P-type Ca2+^{2+} pump located in the Golgi apparatus that plays a key role in the secretory pathway. Our results show that mRNA expression levels of SPCA1 are significantly increased in A7r5 cells cultured in high glucose (25.0 mM)-supplemented medium compared with normal glucose (5.55 mM)-supplemented medium. SPCA1 protein expression levels and thapsigargin-insensitive Ca2+^{2+}-dependent ATPase activity were also consistent with a higher than normal expression level of SPCA1 in high-glucose-cultured A7r5 cells. Analysis of AVP (arginine-vasopressin)-induced cytosolic Ca2+^{2+} transients in A7r5 cells (after pre-treatment with thapsigargin) showed faster rise and decay phases in cells grown in high glucose medium compared with cells grown in normal glucose medium, supporting the observation of increased SPCA expression/activity. The significant levels of both Ca2+^{2+}-ATPase activity and AVP-induced Ca2+^{2+} transients, in the presence of thapsigargin, indicate that SPCA must play a significant role in Ca2+^{2+} uptake within VSMCs. We therefore propose that, if such increases in SPCA expression and activity also occur in primary VSMCs, this may play a substantial role in the aetiology of diabetes mellitus-associated vascular disease, due to alterations in Ca2+^{2+} homoeostasis within the Golgi apparatus

    Surface topography of hydroxyapatite affects ROS17/2.8 cells response

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    Hydroxyapatite (HA) has been used in orthopedic, dental, and maxillofacial surgery as a bone substitute. The aim of this investigation was to study the effect of surface topography produced by the presence of microporosity on cell response, evaluating: cell attachment, cell morphology, cell proliferation, total protein content, and alkaline phosphatase (ALP) activity. HA discs with different percentages of microporosity (< 5%, 15%, and 30%) were confected by means of the combination of uniaxial powder pressing and different sintering conditions. ROS17/2.8 cells were cultured on HA discs. For the evaluation of attachment, cells were cultured for two hours. Cell morphology was evaluated after seven days. After seven and fourteen days, cell proliferation, total protein content, and ALP activity were measured. Data were compared by means of ANOVA and Duncan’s multiple range test, when appropriate. Cell attachment (p = 0.11) and total protein content (p = 0.31) were not affected by surface topography. Proliferation after 7 and 14 days (p = 0.0007 and p = 0.003, respectively), and ALP activity (p = 0.0007) were both significantly decreased by the most irregular surface (HA30). These results suggest that initial cell events were not affected by surface topography, while surfaces with more regular topography, as those present in HA with 15% or less of microporosity, favored intermediary and final events such as cell proliferation and ALP activity

    Communication issues in requirements elicitation: A content analysis of stakeholder experiences

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    The gathering of stakeholder requirements comprises an early, but continuous and highly critical stage in system development. This phase in development is subject to a large degree of error, influenced by key factors rooted in communication problems. This pilot study builds upon an existing theory-based categorisation of these problems through presentation of a four-dimensional framework on communication. Its structure is validated through a content analysis of interview data, from which themes emerge, that can be assigned to the dimensional categories, highlighting any problematic areas. The paper concludes with a discussion on the utilisation of the framework for requirements elicitation exercises

    High Effective Coverage of Vector Control Interventions in Children After Achieving Low Malaria Transmission in Zanzibar, Tanzania.

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    \ud \ud Formerly a high malaria transmission area, Zanzibar is now targeting malaria elimination. A major challenge is to avoid resurgence of malaria, the success of which includes maintaining high effective coverage of vector control interventions such as bed nets and indoor residual spraying (IRS). In this study, caretakers' continued use of preventive measures for their children is evaluated, following a sharp reduction in malaria transmission. A cross-sectional community-based survey was conducted in June 2009 in North A and Micheweni districts in Zanzibar. Households were randomly selected using two-stage cluster sampling. Interviews were conducted with 560 caretakers of under-five-year old children, who were asked about perceptions on the malaria situation, vector control, household assets, and intention for continued use of vector control as malaria burden further decreases. Effective coverage of vector control interventions for under-five children remains high, although most caretakers (65%; 363/560) did not perceive malaria as presently being a major health issue. Seventy percent (447/643) of the under-five children slept under a long-lasting insecticidal net (LLIN) and 94% (607/643) were living in houses targeted with IRS. In total, 98% (628/643) of the children were covered by at least one of the vector control interventions. Seasonal bed-net use for children was reported by 25% (125/508) of caretakers of children who used bed nets. A high proportion of caretakers (95%; 500/524) stated that they intended to continue using preventive measures for their under-five children as malaria burden further reduces. Malaria risk perceptions and different perceptions of vector control were not found to be significantly associated with LLIN effective coverage While the majority of caretakers felt that malaria had been reduced in Zanzibar, effective coverage of vector control interventions remained high. Caretakers appreciated the interventions and recognized the value of sustaining their use. Thus, sustaining high effective coverage of vector control interventions, which is crucial for reaching malaria elimination in Zanzibar, can be achieved by maintaining effective delivery of these interventions

    The application of deep eutectic solvent ionic liquids for environmentally-friendly dissolution and recovery of precious metals

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    publisher: Elsevier articletitle: The application of deep eutectic solvent ionic liquids for environmentally-friendly dissolution and recovery of precious metals journaltitle: Minerals Engineering articlelink: http://dx.doi.org/10.1016/j.mineng.2015.09.026 content_type: article copyright: Copyright © 2015 The Authors. Published by Elsevier Ltd.© 2015 Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

    Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

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    Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection
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