946 resultados para Direct methanol fuel cell


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The underlying generic properties of {alpha}β TCRs that control MHC restriction remain largely unresolved. To investigate MHC restriction, we have examined the CTL response to a viral epitope that binds promiscuously to two human leukocyte Ags (HLAs) that differ by a single amino acid at position 156. Individuals expressing either HLA-B*3501 (156Leucine) or HLA-B*3508 (156Arginine) showed a potent CTL response to the 407HPVGEADYFEY417 epitope from EBV. Interestingly, the response was characterized by highly restricted TCR β-chain usage in both HLA-B*3501+ and HLA-B*3508+ individuals; however, this conserved TRBV9+ β-chain was associated with distinct TCR {alpha}-chains depending upon the HLA-B*35 allele expressed by the virus-exposed host. Functional assays confirmed that TCR {alpha}-chain usage determined the HLA restriction of the CTLs. Structural studies revealed significant differences in the mobility of the peptide when bound to HLA-B*3501 or HLA-B*3508. In HLA-B*3501, the bulged section of the peptide was disordered, whereas in HLA-B*3508 the bulged epitope adopted an ordered conformation. Collectively, these data demonstrate not only that mobile MHC-bound peptides can be highly immunogenic but can also stimulate an extremely biased TCR repertoire. In addition, TCR {alpha}-chain usage is shown to play a critical role in controlling MHC restriction between closely related allomorphs.

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Since the oil crisis of 1973 considerable interest has been shown in the production of liquid fuels from alternative sources. In particular processes utilizing coal as the feedstock have received considerable interest. These processes can be divided into direct and indirect liquefaction and pyrolysis. This thesis describes the modelling of indirect coal liquefaction processes for the purpose of performing technical and economic assessment of the production of liquid fuels from coal and lignite, using a variety of gasification and synthesis gas liquefaction technologies. The technologies were modeled on a 'step model' basis where a step is defined as a combination of individual unit operations which together perform a significant function on the process streams, such as a methanol synthesis step or a gasification and physical gas cleaning step. Sample results of the modelling, covering a wide range of gasifiers, liquid synthesis processes and products are presented in this thesis. Due to the large number of combinations of gasifier, liquid synthesis processes, products and economic sensitivity cases, a complete set of results is impractical to present in a single publication. The main results show that methanol is the cheapest fuel to produce from coal followed by fuel alcohol, diesel from the Shell Middle Distillate Synthesis process,gasoline from Mobil Methanol to Gasoline (MTG) process, diesel from the Mobil Methanol Olefins Gasoline Diesel (MOGD) process and finally gasoline from the same process. Some variation in production costs of all the products was shown depending on type of gasifier chosen and feedstock.

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Organismal development, homeostasis, and pathology are rooted in inherently probabilistic events. From gene expression to cellular differentiation, rates and likelihoods shape the form and function of biology. Processes ranging from growth to cancer homeostasis to reprogramming of stem cells all require transitions between distinct phenotypic states, and these occur at defined rates. Therefore, measuring the fidelity and dynamics with which such transitions occur is central to understanding natural biological phenomena and is critical for therapeutic interventions.

While these processes may produce robust population-level behaviors, decisions are made by individual cells. In certain circumstances, these minuscule computing units effectively roll dice to determine their fate. And while the 'omics' era has provided vast amounts of data on what these populations are doing en masse, the behaviors of the underlying units of these processes get washed out in averages.

Therefore, in order to understand the behavior of a sample of cells, it is critical to reveal how its underlying components, or mixture of cells in distinct states, each contribute to the overall phenotype. As such, we must first define what states exist in the population, determine what controls the stability of these states, and measure in high dimensionality the dynamics with which these cells transition between states.

To address a specific example of this general problem, we investigate the heterogeneity and dynamics of mouse embryonic stem cells (mESCs). While a number of reports have identified particular genes in ES cells that switch between 'high' and 'low' metastable expression states in culture, it remains unclear how levels of many of these regulators combine to form states in transcriptional space. Using a method called single molecule mRNA fluorescent in situ hybridization (smFISH), we quantitatively measure and fit distributions of core pluripotency regulators in single cells, identifying a wide range of variabilities between genes, but each explained by a simple model of bursty transcription. From this data, we also observed that strongly bimodal genes appear to be co-expressed, effectively limiting the occupancy of transcriptional space to two primary states across genes studied here. However, these states also appear punctuated by the conditional expression of the most highly variable genes, potentially defining smaller substates of pluripotency.

Having defined the transcriptional states, we next asked what might control their stability or persistence. Surprisingly, we found that DNA methylation, a mark normally associated with irreversible developmental progression, was itself differentially regulated between these two primary states. Furthermore, both acute or chronic inhibition of DNA methyltransferase activity led to reduced heterogeneity among the population, suggesting that metastability can be modulated by this strong epigenetic mark.

Finally, because understanding the dynamics of state transitions is fundamental to a variety of biological problems, we sought to develop a high-throughput method for the identification of cellular trajectories without the need for cell-line engineering. We achieved this by combining cell-lineage information gathered from time-lapse microscopy with endpoint smFISH for measurements of final expression states. Applying a simple mathematical framework to these lineage-tree associated expression states enables the inference of dynamic transitions. We apply our novel approach in order to infer temporal sequences of events, quantitative switching rates, and network topology among a set of ESC states.

Taken together, we identify distinct expression states in ES cells, gain fundamental insight into how a strong epigenetic modifier enforces the stability of these states, and develop and apply a new method for the identification of cellular trajectories using scalable in situ readouts of cellular state.

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Purpose: To investigate the effect of Allium sativum (garlic) methanol extract on viability and apoptosis of human leukemic cells. Methods: Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay at concentrations of 3.125, 6.25, 12.5, 25, 50, 100, 200, 400 and 800 ug/mL of Allium sativum extract following 48-h treatment on U-937, Jurkat Clone E6-1 and K-562 cell lines. The mode of cell death was determined by Annexin V-FITC staining and analyzed by flow cytometry. Results: The results show that the half-maximal inhibitory concentration (IC50) of A. sativum on U-937, Jurkat Clone E6-1, K-562 cell lines was 105 ± 2.21, 489 ± 4.51 and 455 ± 3.13 μg/mL, respectively, compared with negative control, while apoptosis was 17.93 ± 0.95 % for U-937 cells (p ≤ 0.05), 38.37 ± 1.88 % for Jurkat Clone E6-1 cells (p ≤ 0.001) and 16.37 ± 1.10 % for K-562 cells. A majority of the cells were inhibited by the extract via apoptosis. Only U-937 cells (6.87 ± 0.65 %) showed significant necrosis compared to negative control (p ≤ 0.05). Conclusion: K-562 cells are the most resistant against garlic extract, in contrast to Jurkat Clone E6-1 cells. Garlic extract does not induce necrosis in Jurkat Clone E6-1 and K-562 cells.

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The goal of the thesis "Conversion of a Micro, Glow-Ignition, Two-Stroke Engine from Nitromethane-Methanol Blend Fuel to Military Jet Propellant (JP-8)" was to demonstrate the ability to operate a small engine on JP-8 and was completed in two phases. The first phase included choosing, developing a test stand for, and baseline testing a nitromethane-methanol-fueled engine. The chosen engine was an 11.5 cc, glow-ignition, two-stroke engine designed for remote-controlled helicopters. A micro engine test stand was developed to load and motor the engine. Instrumentation specific to the low flow rates and high speeds of the micro engine was developed and used to document engine behavior. The second phase included converting the engine to operate on JP-8, completing JP-8-fueled steady-state testing, and comparing the performance of the JP-8-fueled engine to the nitromethane-methanol-fueled engine. The conversion was accomplished through a novel crankcase heating method; by heating the crankcase for an extended period of time, a flammable fuel-air mixture was generated in the crankcase scavenged engine, which greatly improved starting times. To aid in starting and steady-state operation, yttrium-zirconia impregnated resin (i.e. ceramic coating) was applied to the combustion surfaces. This also improved the starting times of the JP-8-fueled engine and ultimately allowed for a 34-second starting time. Finally, the steady-state data from both the nitromethane-methanol and JP-8-fueled micro engine were compared. The JP-8-fueled engine showed signs of increased engine friction while having higher indicated fuel conversion efficiency and a higher overall system efficiency. The minimal ability of JP-8 to cool the engine via evaporative effects, however, created the necessity of increased cooling air flow. The conclusion reached was that JP-8-fueled micro engines could be viable in application, but not without additional research being conducted on combustion phenomenon and cooling requirements.

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Nowadays the development of new Internal Combustion Engines is mainly driven by the need to reduce tailpipe emissions of pollutants, Green-House Gases and avoid the fossil fuels wasting. The design of dimension and shape of the combustion chamber together with the implementation of different injection strategies e.g., injection timing, spray targeting, higher injection pressure, play a key role in the accomplishment of the aforementioned targets. As far as the match between the fuel injection and evaporation and the combustion chamber shape is concerned, the assessment of the interaction between the liquid fuel spray and the engine walls in gasoline direct injection engines is crucial. The use of numerical simulations is an acknowledged technique to support the study of new technological solutions such as the design of new gasoline blends and of tailored injection strategies to pursue the target mixture formation. The current simulation framework lacks a well-defined best practice for the liquid fuel spray interaction simulation, which is a complex multi-physics problem. This thesis deals with the development of robust methodologies to approach the numerical simulation of the liquid fuel spray interaction with walls and lubricants. The accomplishment of this task was divided into three tasks: i) setup and validation of spray-wall impingement three-dimensional CFD spray simulations; ii) development of a one-dimensional model describing the liquid fuel – lubricant oil interaction; iii) development of a machine learning based algorithm aimed to define which mixture of known pure components mimics the physical behaviour of the real gasoline for the simulation of the liquid fuel spray interaction.

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The raft hypothesis proposes that microdomains enriched in sphingolipids, cholesterol, and specific proteins are transiently formed to accomplish important cellular tasks. Equivocally, detergent-resistant membranes were initially assumed to be identical to membrane rafts, because of similarities between their compositions. In fact, the impact of detergents in membrane organization is still controversial. Here, we use phase contrast and fluorescence microscopy to observe giant unilamellar vesicles (GUVs) made of erythrocyte membrane lipids (erythro-GUVs) when exposed to the detergent Triton X-100 (TX-100). We clearly show that TX-100 has a restructuring action on biomembranes. Contact with TX-100 readily induces domain formation on the previously homogeneous membrane of erythro-GUVs at physiological and room temperatures. The shape and dynamics of the formed domains point to liquid-ordered/liquid-disordered (Lo/Ld) phase separation, typically found in raft-like ternary lipid mixtures. The Ld domains are then separated from the original vesicle and completely solubilized by TX-100. The insoluble vesicle left, in the Lo phase, represents around 2/3 of the original vesicle surface at room temperature and decreases to almost 1/2 at physiological temperature. This chain of events could be entirely reproduced with biomimetic GUVs of a simple ternary lipid mixture, 2:1:2 POPC/SM/chol (phosphatidylcholine/sphyngomyelin/cholesterol), showing that this behavior will arise because of fundamental physicochemical properties of simple lipid mixtures. This work provides direct visualization of TX-100-induced domain formation followed by selective (Ld phase) solubilization in a model system with a complex biological lipid composition.

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Cyclosporine, a drug used in immunosuppression protocols for hematopoietic stem cell transplantation that has a narrow therapeutic index, may cause various adverse reactions, including nephrotoxicity. This has a direct clinical impact on the patient. This study aims to summarize available evidence in the scientific literature on the use of cyclosporine in respect to its risk factor for the development of nephrotoxicity in patients submitted to hematopoietic stem cell transplantation. A systematic review was made with the following electronic databases: PubMed, Web of Science, Embase, Scopus, CINAHL, LILACS, SciELO and Cochrane BVS. The keywords used were: bone marrow transplantation OR stem cell transplantation OR grafting, bone marrow AND cyclosporine OR cyclosporin OR risk factors AND acute kidney injury OR acute kidney injuries OR acute renal failure OR acute renal failures OR nephrotoxicity. The level of scientific evidence of the studies was classified according to the Oxford Centre for Evidence Based Medicine. The final sample was composed of 19 studies, most of which (89.5%) had an observational design, evidence level 2B and pointed to an incidence of nephrotoxicity above 30%. The available evidence, considered as good quality and appropriate for the analyzed event, indicates that cyclosporine represents a risk factor for the occurrence of nephrotoxicity, particularly when combined with amphotericin B or aminoglycosides, agents commonly used in hematopoietic stem cell transplantation recipients.

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During the last ten years, graphene oxide has been explored in many applications due to its remarkable electroconductivity, thermal properties and mobility of charge carriers, among other properties. As discussed in this review, the literature suggests that a total characterization of graphene oxide must be conducted because oxidation debris (synthesis impurities) present in the graphene oxides could act as a graphene oxide surfactant, stabilizing aqueous dispersions. It is also important to note that the structure models of graphene oxide need to be revisited because of significant implications for its chemical composition and its direct covalent functionalization. Another aspect that is discussed is the need to consider graphene oxide surface chemistry. The hemolysis assay is recommended as a reliable test for the preliminary assessment of graphene oxide toxicity, biocompatibility and cell membrane interaction. More recently, graphene oxide has been extensively explored for drug delivery applications. An important increase in research efforts in this emerging field is clearly represented by the hundreds of related publications per year, including some reviews. Many studies have been performed to explore the graphene oxide properties that enable it to deliver more than one activity simultaneously and to combine multidrug systems with photothermal therapy, indicating that graphene oxide is an attractive tool to overcome hurdles in cancer therapies. Some strategic aspects of the application of these materials in cancer treatment are also discussed. In vitro studies have indicated that graphene oxide can also promote stem cell adhesion, growth and differentiation, and this review discusses the recent and pertinent findings regarding graphene oxide as a valuable nanomaterial for stem cell research in medicine. The protein corona is a key concept in nanomedicine and nanotoxicology because it provides a biomolecular identity for nanomaterials in a biological environment. Understanding protein corona-nanomaterial interactions and their influence on cellular responses is a challenging task at the nanobiointerface. New aspects and developments in this area are discussed.

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ANKHD1 (Ankyrin repeat and KH domain-containing protein 1) is highly expressed and plays an important role in the proliferation and cell cycle progression of multiple myeloma (MM) cells. ANKHD1 downregulation modulates cell cycle gene expression and upregulates p21 irrespective of the TP53 mutational status of MM cell lines. The present study was aimed to investigate the role of ANKHD1 in MM in vitro clonogenicity and in vivo tumourigenicity, as well as the role of ANKHD1 in p21 transcriptional regulation. ANKHD1 silencing in MM cells resulted in significantly low no. of colonies formed and in slow migration as compared to control cells (p < 0.05). Furthermore, in xenograft MM mice models, tumour growth was visibly suppressed in mice injected with ANKHD1 silenced cells compared to the control group. There was a significant decrease in tumour volume (p = 0.006) as well as in weight (p = 0.02) in the group injected with silenced cells compared to those of the control group. Co-immunoprecipitation and chromatin immunoprecipitation (ChIP) assays confirmed the interaction between p21 and ANKHD1. Moreover, overexpression of ANKHD1 downregulated the activity of a p21 promoter in luciferase assays. Decrease in luciferase activity suggests a direct role of ANKHD1 in p21 transcriptional regulation. In addition confocal analysis after U266 cells were treated with Leptomycin B (LMB) for 24 h showed accumulation of ANKHD1 inside the nucleus as compared to untreated cells where ANKHD1 was found to be predominantly in cytoplasm. This suggests ANKHD1 might be shuttling between cytoplasm and nucleus. In conclusion, ANKHD1 promotes MM growth by repressing p21 a potent cell cycle regulator.