Optimization of a Centrifugal Compressor Using the Design of Experiment Technique

Centrifugal compressor performance is affected by many parameters, optimization of which can lead to superior designs. Recognizing the most important parameters affecting performance helps to reduce the optimization process cost. Of the compressor components, the impeller plays the most important role in compressor performance, hence the design parameters affecting this component were considered. A turbocharger centrifugal compressor with vaneless diffuser was studied and the parameters investigated included meridional geometry, rotor blade angle distribution and start location of the main blades and splitters. The diffuser shape was captured as part of the meridional geometry. Applying a novel approach to the problem, full factorial analysis was used to investigate the most effective parameters. The Response Surface Method was then implemented to construct the surrogate models and to recognize the best points over a design space created as based on the Box-Behnken methodology. The results highlighted the factors that affected impeller performance the most. Using the Design of Experiment technique, the model which optimized both efficiency and pressure ratio simultaneously delivered a design with 3% and 11% improvement in each respectively in comparison to the initial impeller at the design point. Importantly, this was not at the expense of sacrificing range, of critical concern in compressor design

Performance Back-deduction from a Loading to Flow Coefficient Map: Application to Radial Turbine

Radial turbine stages are often used for applications requiring off-design operation, as turbocharging for instance. The off-design ability of such stages is commonly analyzed through the traditional turbine map, plotting the reduced mass-flow against the pressure-ratio, for reduced-speed lines. However, some alternatives are possible, such as the flow-coefficient (Ψ ) to loading-coefficient (φ) diagram where the pressure-ratio lines are actually straight lines, very convenient property to perform prediction. A robust method re-creating this map from a predicted Ψ−φ diagram is needed. Recent work has shown that this back-deduction quality, without the use of any loss models, depends on the knowledge of an intermediate pressure-ratio. A modelization of this parameter is then proposed. The comparison with both experimental and CFD results is presented, with quite good agreement for mass flow rate and rotational speed, and for the intermediate pressure ratio. The last part of the paper is dedicated to the application of the intermediate pressure-ratio knowledge to the improvement of the deduction of the pressure ratio lines in the Ψ−φ diagram. Beside this improvement, the back-deduction method of the classical map is structured, applied and evaluated

Prolonged day length exposure improves circadian deficits and survival in a transgenic mouse model of Huntington's disease

The circadian disruption seen in patients of Huntington's disease (HD) is recapitulated in the R6/2 mouse model. As the disease progresses, the activity of R6/2 mice increases dramatically during the rest (light) period and decreases during the active (dark) period, eventually leading to a complete disintegration of rest-activity rhythms by the age of ~16 weeks. The suprachiasmatic nucleus controls circadian rhythms by entraining the rest-activity rhythms to the environmental light-dark cycle. Since R6/2 mice can shift their rest-activity rhythms in response to a jet-lag paradigm and also respond positively to bright light therapy (1000 lx), we investigated whether or not a prolonged day length exposure could reduce their daytime activity and improve their behavioural circadian rhythms. We found that a long-day photoperiod (16 h light/8 h dark cycle; 100 lx) significantly improved the survival of R6/2 female mice by 2.4 weeks, compared to mice kept under standard conditions (12 h light/12 h dark cycle). Furthermore, a long-day photoperiod improved the nocturnality of R6/2 female mice. Mice kept under long-day photoperiod also maintained acrophase in activity rhythms (a parameter of rhythmicity strength) in phase with that of WT mice, even if they were symptomatic. By contrast, a short-day photoperiod (8 h light/16 h dark cycle) was deleterious to R6/2 female mice and further reduced the survival by ~1 week. Together, our results support the idea that light therapy may be beneficial for improving circadian dysfunction in HD patients.This research was supported by a grant from CHDIInc

Climate of origin affects tick (Ixodes ricinus) host-seeking behavior in response to temperature: implications for resilience to climate change?

Climate warming is changing distributions and phenologies of many organisms and may also impact on vectors of disease‐causing pathogens. In Europe, the tick Ixodes ricinus is the primary vector of medically important pathogens (e.g., Borrelia burgdorferi sensu lato, the causative agent of Lyme borreliosis). How might climate change affect I. ricinus host‐seeking behavior (questing)? We hypothesize that, in order to maximize survival, I. ricinus have adapted their questing in response to temperature in accordance with local climates. We predicted that ticks from cooler climates quest at cooler temperatures than those from warmer climates. This would suggest that I. ricinus can adapt and therefore have the potential to be resilient to climate change. I. ricinus were collected from a cline of climates using a latitudinal gradient (northeast Scotland, North Wales, South England, and central France). Under laboratory conditions, ticks were subjected to temperature increases of 1°C per day, from 6 to 15°C. The proportion of ticks questing was recorded five times per temperature (i.e., per day). The theoretical potential to quest was then estimated for each population over the year for future climate change projections. As predicted, more ticks from cooler climates quested at lower temperatures than did ticks from warmer climates. The proportion of ticks questing was strongly associated with key climate parameters from each location. Our projections, based on temperature alone, suggested that populations could advance their activity season by a month under climate change, which has implications for exposure periods of hosts to tick‐borne pathogens. Our findings suggest that I. ricinus have adapted their behavior in response to climate, implying some potential to adapt to climate change. Predictive models of I. ricinus dynamics and disease risk over continental scales would benefit from knowledge of these differences between populations

Progressive gene dose-dependent disruption of the methamphetamine-sensitive circadian oscillator-driven rhythms in a knock-in mouse model of Huntington's disease.

Huntington's disease (HD) is a progressive genetic neurodegenerative disorder characterised by motor and cognitive deficits, as well as sleep and circadian abnormalities. In the R6/2 mouse, a fragment model of HD, rest-activity rhythms controlled by the suprachiasmatic nucleus disintegrate completely by 4months of age. Rhythms driven by a second circadian oscillator, the methamphetamine-sensitive circadian oscillator (MASCO), are disrupted even earlier, and cannot be induced after 2months of age. Here, we studied the effect of the HD mutation on the expression of MASCO-driven rhythms in a more slowly developing, genetically relevant mouse model of HD, the Q175 'knock-in' mouse. We induced expression of MASCO output by administering low dose methamphetamine (0.005%) chronically via the drinking water. We measured locomotor activity in constant darkness in wild-type and Q175 mice at 2 (presymptomatic), 6 (early symptomatic), and 12 (symptomatic) months of age. At 2months, all mice expressed MASCO-driven rhythms, regardless of genotype. At older ages, however, there was a progressive gene dose-dependent deficit in MASCO output in Q175 mice. At 6months of age, these rhythms could be observed in only 45% of heterozygous and 15% of homozygous mice. By 1year of age, 90% of homozygous mice had an impaired MASCO output. There was also an age-dependent disruption of MASCO output seen in wild-type mice. The fact that the progressive deficit in MASCO-driven rhythms in Q175 mice is HD gene dose-dependent suggests that, whatever its role in humans, abnormalities in MASCO output may contribute to the HD circadian phenotype.This work was supported by a grant from CHDI Foundation, Inc. (USA).This is the author accepted manuscript. The final version is available from Elsevier via https://doi.org/10.1016/j.expneurol.2016.09.00

Identification of microRNAs involved in the development and function of follicular dendritic cells

Follicular dendritic cells (FDCs) are key elements of secondary lymphoid organs where they form the stromal component of B-cell follicles. FDCs possess extensive dendritic process that trap intact antigen via Fc and complement receptors on the cell surface. The antigen is displayed to B-cells, providing a basis for selection of high affinity B cells. FDC also have important roles in facilitating the clearance of apoptotic B cells by the secretion of the opsonising factor MFGE8. It is well established that lymphotoxin signalling is required for FDC maturation but the specific details of the molecular mechanisms that regulate FDC development and differentiation are not fully understood. MicroRNAs (miRNAs) are non-coding RNAs of approximately 18-25 nucleotides in length that regulate gene expression at the post-transcriptional level. MiRNAs bind to their target gene transcripts as part of the RNA induced silencing complex and repress translation of the target gene product. The objective of this study was to identify miRNAs that play a role in the development and function of FDCs. An in vivo murine model of FDC de-differentiation was used to provide material for miRNA analysis. By comparison of miRNA profiles from spleen tissue with FDC at different stages of de-differentiation, we would be able to obtain a miRNA signature for mature FDC. Spleens were collected at various time points over a 28 day period following transient blockade of lymphotoxin signalling. A variety of methods were used to profile the miRNAs expressed at different time points during the suppression and recovery of the FDC network. Comparison of the miRNA profiles of spleens containing mature, partially de-differentiated, and fully de-differentiated FDC identified a number of miRNAs that were differentially expressed during FDC de-differentiation. To assess the role of specific miRNAs in FDC development, the mouse FDC-like cell line, FL-YB, was used as an in vitro model system. FL-YB cells were used to perform gain-offunction and loss-of-function studies on selected miRNAs and to assess the effects of various stimuli/conditions on miRNA expression. The effects of different treatments on cell proliferation, morphology and adhesion, and on gene expression by FL-YB, were monitored. Loss-of-function studies for one of the selected miRNA (miR-100-5p) revealed a significant effect on a number of gene transcripts involved in mediation of the germinal centre response (Il-6, Tlr4, Ptgs1/2). These data indicate that miR-100-5p has a role in regulating Il-6, Tlr4 and Ptgs1/2 transcripts. None of these transcripts contain predicted target sites for miR-100-5p and so the effect of miR-100-5p on these transcripts is likely to be indirect. Further studies on these miRNA: target interactions are required to elucidate the mechanisms and biological consequences of miRNA regulation in FDCs

Towards an evolutionary understanding of questing behaviour in the tick Ixodes ricinus

The tick Ixodes ricinus finds its hosts by climbing vegetation and adopting a sit-and-wait tactic. This “questing” behaviour is known to be temperature-dependent, such that questing increases with temperature up to a point where the vapor pressure deficit (drying effect) forces ticks down to rehydrate in the soil or mat layer. Little if any attention has been paid to understanding the questing of ticks from an evolutionary perspective. Here we ask whether populations from colder climatic conditions respond differently in terms of the threshold temperature for questing and the rate of response to a fixed temperature. We find significant variation between populations in the temperature sensitivity of questing, with populations from cooler climates starting questing at lower temperatures than populations from warmer temperatures. Cool climate populations also quest sooner when the temperature is held constant. These patterns are consistent with local adaptation to temperature either through direct selection or acclimation and challenge the use of fixed thresholds for questing in modeling the spread of tick populations. Our results also show how both time and temperature play a role in questing, but we are unable to explain the relationship in terms of degree-time used to model Arthropod development. We find that questing in response to temperature fits well with a quantitative genetic model of the conditional strategy, which reveals how selection on questing may operate and hence may be of value in understanding the evolutionary ecology of questing

Abnormal Photic Entrainment to Phase-Delaying Stimuli in the R6/2 Mouse Model of Huntington's Disease, despite Retinal Responsiveness to Light.

The circadian clock located in the suprachiasmatic nucleus (SCN) in mammals entrains to ambient light via the retinal photoreceptors. This allows behavioral rhythms to change in synchrony with seasonal and daily changes in light period. Circadian rhythmicity is progressively disrupted in Huntington's disease (HD) and in HD mouse models such as the transgenic R6/2 line. Although retinal afferent inputs to the SCN are disrupted in R6/2 mice at late stages, they can respond to changes in light/dark cycles, as seen in jet lag and 23 h/d paradigms. To investigate photic entrainment and SCN function in R6/2 mice at different stages of disease, we first assessed the effect on locomotor activity of exposure to a 15 min light pulse given at different times of the day. We then placed the mice under five non-standard light conditions. These were light cycle regimes (T-cycles) of T21 (10.5 h light/dark), T22 (11 h light/dark), T26 (13 h light/dark), constant light, or constant dark. We found a progressive impairment in photic synchronization in R6/2 mice when the stimuli required the SCN to lengthen rhythms (phase-delaying light pulse, T26, or constant light), but normal synchronization to stimuli that required the SCN to shorten rhythms (phase-advancing light pulse and T22). Despite the behavioral abnormalities, we found that Per1 and c-fos gene expression remained photo-inducible in SCN of R6/2 mice. Both the endogenous drift of the R6/2 mouse SCN to shorter periods and its inability to adapt to phase-delaying changes will contribute to the HD circadian dysfunction

Characterization of the Performance of a Turbocharger Centrifugal Compressor by Component Loss Contributions

The performance of an automotive turbocharger centrifugal compressor has been studied by developing a comprehensive one-dimensional (1D) code as verified through experimental results and a three-dimensional (3D) model. For 1D analysis, the fluid stream in compressor is modeled using governing gas dynamics equations and the loss mechanisms have been investigated and added to the numerical model. The objective is to develop and offer a 1D model which considers all loss mechanisms, slip, blockage and also predicts the surge margin and choke conditions. The model captures all features from inlet duct through to volute discharge. Performance characteristics are obtained using preliminary geometry and the blade characteristics. A 3D numerical model was also created and a viscous solver used for investigating the compressor characteristics. The numerical model results show good agreement with experimental data through compressor pressure ratio and efficiency. The effect of the main compressor dimensions on compressor performance has been investigated for wide operating range and the portions of each loss mechanism in the impeller. Higher pressure ratio is achievable by increasing impeller blade height at outlet, impeller blade angle on inlet, diffuser outlet diameter and by decreasing impeller shroud diameter at inlet and blade angle at outlet. These changes may cause unfavorable consequences such as lower surge margin or shorter operating range which should be compromised with favorable changes. At lower rotational speeds, impeller skin friction mainly impacts the performance and at higher rotational speeds, impeller diffusion, blade loading and recirculation losses are more important. The results allow the share of each loss mechanism to be quantified for different mass flow rates and rotational speed, shedding new light on which losses are most important for which conditions. For a turbocharger, which must operate over a wide range of conditions, these results bring new insight to engineers seeking to optimize the compressor design as part of an internal combustion engine system

Adaptation to experimental jet-lag in R6/2 mice despite circadian dysrhythmia.

The R6/2 transgenic mouse model of Huntington's disease (HD) shows a disintegration of circadian rhythms that can be delayed by pharmacological and non-pharmacological means. Since the molecular machinery underlying the circadian clocks is intact, albeit progressively dysfunctional, we wondered if light phase shifts could modulate the deterioration in daily rhythms in R6/2 mice. Mice were subjected to four x 4 hour advances in light onset. R6/2 mice adapted to phase advances, although angles of entrainment increased with age. A second cohort was subjected to a jet-lag paradigm (6 hour delay or advance in light onset, then reversal after 2 weeks). R6/2 mice adapted to the original shift, but could not adjust accurately to the reversal. Interestingly, phase shifts ameliorated the circadian rhythm breakdown seen in R6/2 mice under normal LD conditions. Our previous finding that the circadian period (tau) of 16 week old R6/2 mice shortens to approximately 23 hours may explain how they adapt to phase advances and maintain regular circadian rhythms. We tested this using a 23 hour period light/dark cycle. R6/2 mice entrained to this cycle, but onsets of activity continued to advance, and circadian rhythms still disintegrated. Therefore, the beneficial effects of phase-shifting are not due solely to the light cycle being closer to the tau of the mice. Our data show that R6/2 mice can adapt to changes in the LD schedule, even beyond the age when their circadian rhythms would normally disintegrate. Nevertheless, they show abnormal responses to changes in light cycles. These might be caused by a shortened tau, impaired photic re-synchronization, impaired light detection and/or reduced masking by evening light. If similar abnormalities are present in HD patients, they may suffer exaggerated jet-lag. Since the underlying molecular clock mechanism remains intact, light may be a useful treatment for circadian dysfunction in HD