353 research outputs found
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Spatio-temporal Evolution of Diesel Sprays at the Early Start of Injection
The impact of injector life on the spatio-temporal evolution of fuel spray quality was optically investigated using high speed imaging techniques. Both new and used injectors, which had been used in intense operation for up to 90,000 miles, were considered in this investigation. Used injectors are prone to wear, deposit formation, and altered internal nozzle flow. High resolution SEM images clearly portray the presence of carbonaceous deposits both at the injector tip as well as within the holes of used injectors. Investigations revealed that used injectors tend to produce a chaotic hole-to-hole variation at the start of each injection, resulting in an asymmetric early fuel spraypenetration pattern in the first 500μs. Often those sprays thatsuffereda reduced spray tippenetration rate at the start of injection also showed off-axis transient expansions, and those sprays appeared to be bulky compared to other sprays. Following the early asymmetric spray penetration phase of injection the retarded sprays undergo rapid acceleration with time, and this transformed the early asymmetric spray pattern into a nearly uniform spray pattern from all the orifices in the quasi-steady state regime. The hole-to-hole penetration variations and the resultant asymmetric spray structure at the early start are therefore short lived transient phenomena. However if the radial expansion of the spray is large during the early phase, the radially expanded plume remains almost at the same radial location due to lack of local axial momentum, even after different time instants of spray tip propagation. This appears as a bulge to the spray and can eventually end up as a stationary local pocket of fuel vapor close to the nozzle for the entire duration of injection. This may alter the ignition, flame lift-off and entrainment characteristics of sprays injected from used or deposit rich injectors
Purification and Reconstitution of the Glutamate Carrier GltT of the Thermophilic Bacterium Bacillus stearothermophilus
An affinity tag consisting of six adjacent histidine residues followed by an enterokinase cleavage site was genetically engineered at the N-terminus of the glutamate transport protein GltT of the thermophilic bacterium Bacillus stearothermophilus. The fusion protein was expressed in Escherichia coli and shown to transport glutamate. The highest levels of expression were observed in E. coli strain DH5α grown on rich medium. The protein could be purified in a single step by Ni2+-NTA affinity chromatography after solubilization of the cytoplasmic membranes with the detergent Triton X100. Purified GltT was reconstituted in an active state in liposomes prepared from E. coli phospholipids. The protein was reconstituted in detergent-treated preformed liposomes, followed by removal of the detergent with polystyrene beads. Active reconstitution was realized with a wide range of Triton X100 concentrations. Neither the presence of glycerol, phospholipids, nor substrates of the transporter was necessary during the purification and reconstitution procedure to keep the enzyme in an active state. In B. stearothermophilus, GltT translocates glutamate in symport with protons or sodium ions. In membrane vesicles derived from E. coli cells expressing GltT, the Na+ ion dependency seems to be lost, suggesting a role for the lipid environment in the cation specificity. In agreement with the last observation, glutamate transport catalyzed by purified GltT reconstituted in E. coli phospholipid is driven by an electrochemical gradient of H+ but not of Na+.
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Combustion of Ligaments and Droplets Expelled after the End of Injection in a Multi-hole Diesel Injector
Experimental investigations were carried out to study the end of injection spray characteristics using a number of production grade multi-hole common-rail injectors. These injectors were taken from light-duty diesel vehicles that are currently in operation on the UK roads and have done different mileages. All the production injectors suffered expulsions of ligaments and droplets after the end of injection(aeoi). It is shown that injector age/mileage has very little effect on the amount of ligaments and droplets ejected from production injectors compared to injection-to-injection variations in the amount of post-injection expulsions. Brand new production injectors also show the presence of these post-injection expulsions after every injection, which is not a desired feature of the modern solenoid actuated common-rail fuel injection system. Subsequent combustion of these post-injection ligaments and droplets lasted up to 25ms after the end of fuel injection in our high pressure, high temperature experiments, and this would contribute to engine-out soot and unburned hydrocarbon (ubhc) emissions in a firing engine.This work has been sponsored by shell Global Solutions (UK) and EPSRC
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Investigation of Spray Angle Measurement Techniques
The in-cylinder fluid-dynamic processes of fuel injection and air entrainment influence the structure and shape of evolving fuel sprays, which can subsequently alter the ignition, combustion and pollutant formation processes in diesel engines. Different spray angle detection methods have been used in the literature to investigate the global and local spray characteristics. In this work, the five most widely used diesel spray angle detection methods were identified, and used to evaluate the characteristic features of each detection method: methods with a detection range based on the spray penetration length, methods with a fixed detection range in the near and far-field spray region, triangular-based methods, and methods based on averaging local data points. The sprays were acquired from our spray chamber and processed with different thresholding techniques to explore the differences between spray angle detection methods. All five methods generated a similar global trend of spray angle variation for temporally evolving sprays over the complete injection period. However, the actual spray angle values detected by each method were not always comparable. The differences in spray angle values between the different detection methods were larger during the early start of injection, and these differences systematically decreased as the spray approached a steady-state. The methods that detected the angle in the far-field demonstrated lower spatiotemporal variability when compared to the methods that detected the angle in the near-field. An assessment ofthecomparabilitybetweenangledetectionmethodswasmadeandtheoutcomeprovidesguidanceforthe selection of the spray angle detection method.Engineering and Physical Sciences Research Council in the UK (EPSRC
The effect of on-line position correction on the dose distribution in focal radiotherapy for bladder cancer
<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to determine the dosimetric effect of on-line position correction for bladder tumor irradiation and to find methods to predict and handle this effect.</p> <p>Methods</p> <p>For 25 patients with unifocal bladder cancer intensity modulated radiotherapy (IMRT) with 5 beams was planned. The requirement for each plan was that 99% of the target volume received 95% of the prescribed dose. Tumor displacements from -2.0 cm to 2.0 cm in each dimension were simulated, using 0.5 cm increments, resulting in 729 simulations per patient. We assumed that on-line correction for the tumor was applied perfectly. We determined the correlation between the change in D<sub>99% </sub>and the change in path length, which is defined here as the distance from the skin to the isocenter for each beam. In addition the margin needed to avoid underdosage was determined and the probability that an underdosage occurs in a real treatment was calculated.</p> <p>Results</p> <p>Adjustments for tumor displacement with perfect on-line position correction resulted in an altered dose distribution. The altered fraction dose to the target varied from 91.9% to 100.4% of the prescribed dose. The mean D<sub>99% </sub>(± SD) was 95.8% ± 1.0%. There was a modest linear correlation between the difference in D<sub>99% </sub>and the change in path length of the beams after correction (R<sup>2 </sup>= 0.590). The median probability that a systematic underdosage occurs in a real treatment was 0.23% (range: 0 - 24.5%). A margin of 2 mm reduced that probability to < 0.001% in all patients.</p> <p>Conclusion</p> <p>On-line position correction does result in an altered target coverage, due to changes in average path length after position correction. An extra margin can be added to prevent underdosage.</p
Patterns of Recurrence and Survival After Pelvic Treatment for Locally Advanced Penile Cancer
BACKGROUND: Penile cancer (PeCa) is rare, and the survival of patients with advanced disease remains poor. A better understanding of where treatment fails could aid the development of new treatment strategies. OBJECTIVE: To describe the disease course after pelvic lymph node (LN) treatment for PeCa. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analysed 228 patients who underwent pelvic LN treatment with curative intent from 1969 to 2016. The main treatment modalities were neoadjuvant chemotherapy, chemoradiation, and pelvic LN dissection. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In the case of multiple recurrence locations, the most distant location was taken and recorded as follows: local (penis), regional (inguinal and pelvic LN), and distant (any other location). A competing risk analysis was used to calculate the time to recurrence per location, and a Kaplan-Meier analysis was used for overall survival (OS). RESULTS AND LIMITATIONS: The median follow-up of the surviving patients was 79 mo. The reason for pelvic treatment was pelvic involvement on imaging (29%), two or more tumour-positive inguinal LNs (61%), or inguinal extranodal extension (52%). More than half of the patients (61%) developed a recurrence. The median recurrence-free survival was 11 mo. The distribution was local in 9%, regional in 27%, and distant in 64% of patients. The infield control rate of nonsystemically treated patients was 61% (113/184). From the start of pelvic treatment, the median OS was 17 mo (95% confidence interval 12–22). After regional or distant recurrence, all but one patient died of PeCa with median OS after a recurrence of 4.4 (regional) and 3.1 (distant) mo. This study is limited by its retrospective nature. CONCLUSIONS: The prognosis of PeCa patients treated on their pelvis who recur despite locoregional treatment is poor. The tendency for systemic spread emphasises the need for more effective systemic treatment strategies. PATIENT SUMMARY: In this report, we looked at the outcomes of penile cancer patients in an expert centre undergoing various treatments on their pelvis. We found that survival is poor after recurrence despite locoregional treatment. Therefore, better systemic treatments are necessary
High-dimensional analysis of the aging immune system: verification of age-associated differences in immune signaling responses in healthy donors.
BACKGROUND
Single-cell network profiling (SCNP) is a multiparametric flow cytometry-based approach that simultaneously measures evoked signaling in multiple cell subsets. Previously, using the SCNP approach, age-associated immune signaling responses were identified in a cohort of 60 healthy donors.
METHODS
In the current study, a high-dimensional analysis of intracellular signaling was performed by measuring 24 signaling nodes in 7 distinct immune cell subsets within PBMCs in an independent cohort of 174 healthy donors [144 elderly (>65 yrs); 30 young (25-40 yrs)].
RESULTS
Associations between age and 9 immune signaling responses identified in the previously published 60 donor cohort were confirmed in the current study. Furthermore, within the current study cohort, 48 additional immune signaling responses differed significantly between young and elderly donors. These associations spanned all profiled modulators and immune cell subsets.
CONCLUSIONS
These results demonstrate that SCNP, a systems-based approach, can capture the complexity of the cellular mechanisms underlying immunological aging. Further, the confirmation of age associations in an independent donor cohort supports the use of SCNP as a tool for identifying reproducible predictive biomarkers in areas such as vaccine response and response to cancer immunotherapies
Darwin wasps: a new name heralds renewed efforts to unravel the evolutionary history of Ichneumonidae
The parasitoid wasp family Ichneumonidae is arguably one of the groups for which current knowledge lags most strongly behind their enormous diversity. In a five-day meeting in Basel (Switzerland) in June 2019, 22 researchers from 14 countries met to discuss the most important issues in ichneumonid research, including increasing the speed of species discovery, resolving higher-level relationships, and studying the radiation of these parasitoids onto various host groups through time. All agreed that it is time to advertise ichneumonid research more broadly and thereby attract young talents to this group for which specialists are sorely lacking, as well as increase public awareness about their exciting biology and ecological impact. In order to popularize the group, we here suggest a new vernacular name for the family, “Darwin wasps”, to reflect the pivotal role they played in convincing Charles Darwin that not all of creation could have been created by a benevolent god. We hope that the name catches on, and that Darwin wasps start buzzing more loudly across all disciplines of biology
Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle.
Chaperones TAPBPR and tapasin associate with class I major histocompatibility complexes (MHC-I) to promote optimization (editing) of peptide cargo. Here, we use solution NMR to investigate the mechanism of peptide exchange. We identify TAPBPR-induced conformational changes on conserved MHC-I molecular surfaces, consistent with our independently determined X-ray structure of the complex. Dynamics present in the empty MHC-I are stabilized by TAPBPR and become progressively dampened with increasing peptide occupancy. Incoming peptides are recognized according to the global stability of the final pMHC-I product and anneal in a native-like conformation to be edited by TAPBPR. Our results demonstrate an inverse relationship between MHC-I peptide occupancy and TAPBPR binding affinity, wherein the lifetime and structural features of transiently bound peptides control the regulation of a conformational switch located near the TAPBPR binding site, which triggers TAPBPR release. These results suggest a similar mechanism for the function of tapasin in the peptide-loading complex
Melanoma NOS1 expression promotes dysfunctional IFN signaling.
In multiple forms of cancer, constitutive activation of type I IFN signaling is a critical consequence of immune surveillance against cancer; however, PBMCs isolated from cancer patients exhibit depressed STAT1 phosphorylation in response to IFN-α, suggesting IFN signaling dysfunction. Here, we demonstrated in a coculture system that melanoma cells differentially impairs the IFN-α response in PBMCs and that the inhibitory potential of a particular melanoma cell correlates with NOS1 expression. Comparison of gene transcription and array comparative genomic hybridization (aCGH) between melanoma cells from different patients indicated that suppression of IFN-α signaling correlates with an amplification of the NOS1 locus within segment 12q22-24. Evaluation of NOS1 levels in melanomas and IFN responsiveness of purified PBMCs from patients indicated a negative correlation between NOS1 expression in melanomas and the responsiveness of PBMCs to IFN-α. Furthermore, in an explorative study, NOS1 expression in melanoma metastases was negatively associated with patient response to adoptive T cell therapy. This study provides a link between cancer cell phenotype and IFN signal dysfunction in circulating immune cells
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