59 research outputs found

    The initiation and development of combustion under cold idling conditions using a glow plug in diesel engines

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    Factors determining the success or failure of combustion initiation using a glow plug have been investigated through experimental work on a single cylinder, common rail diesel engine with a geometric compression ratio of 15.5, and a quiescent combustion bomb with optical access. A glow plug was required to avoid engine misfires when bulk gas temperature at the start of injection was less than 413 C. The distance between the glow plug and the spray edge, the glow plug temperature, and the bulk gas temperature were important factors in meeting two requirements for successful ignition: a minimum local temperature of 413 C and a minimum air/fuel vapour equivalence ratio of 0.15–0.35

    Targeting small molecule drugs to T cells with antibody-directed cell-penetrating gold nanoparticles

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    We sought to develop a nanoparticle vehicle that could efficiently deliver small molecule drugs to target lymphocyte populations. The synthesized amphiphilic organic ligand-protected gold nanoparticles (amph-NPs) were capable of sequestering large payloads of small molecule drugs within hydrophobic pockets of their ligand shells. These particles exhibit membrane-penetrating activity in mammalian cells, and thus enhanced uptake of a small molecule TGF-β inhibitor in T cells in cell culture. By conjugating amph-NPs with targeting antibodies or camelid-derived nanobodies, the particles' cell-penetrating properties could be temporarily suppressed, allowing targeted uptake in specific lymphocyte subpopulations. Degradation of the protein targeting moieties following particle endocytosis allowed the NPs to recover their cell-penetrating activity in situ to enter the cytoplasm of T cells. In vivo, targeted amph-NPs showed 40-fold enhanced uptake in CD8+ T cells relative to untargeted particles, and delivery of TGF-β inhibitor-loaded particles to T cells enhanced their cytokine polyfunctionality in a cancer vaccine model. Thus, this system provides a facile approach to concentrate small molecule compounds in target lymphocyte populations of interest for immunotherapy in cancer and other diseases.Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Contract W911NF-13-D-0001)Melanoma Research AllianceNational Cancer Institute (U.S.) (David H. Koch Institute for Integrative Cancer Research at MIT. (Support (Core) Grant P30-CA14051)National Institutes of Health (U.S.) (Grant CA174795)National Institutes of Health (U.S.) (Grant CA172164)Horizon 2020 Framework Programme (European Commission). FutureNanoNeeds Projec

    Gold Nanostar-Coated Polystyrene Beads as Multifunctional Nanoprobes for SERS Bioimaging

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    Hybrid colloidal nanocomposites comprising polystyrene beads and plasmonic gold nanostars are reported as multifunctional optical nanoprobes. Such self-assembled structures are excellent Raman enhancers for bioapplications as they feature plasmon modes in the near-infrared "first biological transparency window". In this proof of concept study, we used 4-mercaptobenzoic acid as a Raman-active molecule to optimize the density of gold nanostars on polystyrene beads, improving SERS performance and thereby allowing in vitro cell culture imaging. Interestingly, intermediate gold nanostar loadings were found to yield higher SERS response, which was confirmed by electromagnetic modeling. These engineered hybrid nanostructures notably improve the possibilities of using gold nanostars as SERS tags. Additionally, when fluorescently labeled polystyrene beads are used as colloidal carriers, the composite particles can be applied as promising tools for multimodal bioimaging

    Renal clearable catalytic gold nanoclusters for in vivo disease monitoring

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    Ultra-small gold nanoclusters (AuNCs) have emerged as agile probes for in vivo imaging, as they exhibit exceptional tumour accumulation and efficient renal clearance properties. However, their intrinsic catalytic activity, which can enable increased detection sensitivity, has yet to be explored for in vivo sensing. By exploiting the peroxidase-mimicking activity of AuNCs and the precise nanometer size filtration of the kidney, we designed multifunctional protease nanosensors that respond to disease microenvironments to produce a direct colorimetric urinary readout of disease state in less than 1 h. We monitored the catalytic activity of AuNCs in collected urine of a mouse model of colorectal cancer where tumour-bearing mice showed a 13-fold increase in colorimetric signal compared to healthy mice. Nanosensors were eliminated completely through hepatic and renal excretion within 4 weeks after injection with no evidence of toxicity. We envision that this modular approach will enable rapid detection of a diverse range of diseases by exploiting their specific enzymatic signatures

    A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation

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    Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

    A multilaboratory comparison of calibration accuracy and the performance of external references in analytical ultracentrifugation.

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    Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

    A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation

    Get PDF
    Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

    Experimental validation of a combustion kinetics based multi-zone model for natural gas-diesel RCCI engines

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    This paper presents the validation results of TNO's combustion model designed to support RCCI control development. In-depth validation was performed on a multi-cylinder heavy-duty engine operating in RCCI mode on natural gas and diesel fuel. It was shown that the adopted approach is able to represent experimental pressure trace with the accuracy within cycle-to-cycle variations at low to mid-range engine loads. The highest load case showed slightly higher deviation. The modeled emissions remained at similar levels as exhaust manifold sampling results (except for NOx which was under-predicted). Furthermore, performance indicators such as IMEP and CA50 showed good agreement with measured values

    Experimental validation of a combustion kinetics based multi-zone model for natural gas-diesel RCCI engines

    No full text
    This paper presents the validation results of TNO's combustion model designed to support RCCI control development. In-depth validation was performed on a multi-cylinder heavy-duty engine operating in RCCI mode on natural gas and diesel fuel. It was shown that the adopted approach is able to represent experimental pressure trace with the accuracy within cycle-to-cycle variations at low to mid-range engine loads. The highest load case showed slightly higher deviation. The modeled emissions remained at similar levels as exhaust manifold sampling results (except for NOx which was under-predicted). Furthermore, performance indicators such as IMEP and CA50 showed good agreement with measured values
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