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

Mutant calreticulin knockin mice develop thrombocytosis and myelofibrosis without a stem cell self-renewal advantage.

Somatic mutations in the endoplasmic reticulum chaperone calreticulin (CALR) are detected in approximately 40% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF). Multiple different mutations have been reported, but all result in a +1-bp frameshift and generate a novel protein C terminus. In this study, we generated a conditional mouse knockin model of the most common CALR mutation, a 52-bp deletion. The mutant novel human C-terminal sequence is integrated into the otherwise intact mouse CALR gene and results in mutant CALR expression under the control of the endogenous mouse locus. CALRdel/+ mice develop a transplantable ET-like disease with marked thrombocytosis, which is associated with increased and morphologically abnormal megakaryocytes and increased numbers of phenotypically defined hematopoietic stem cells (HSCs). Homozygous CALRdel/del mice developed extreme thrombocytosis accompanied by features of MF, including leukocytosis, reduced hematocrit, splenomegaly, and increased bone marrow reticulin. CALRdel/+ HSCs were more proliferative in vitro, but neither CALRdel/+ nor CALRdel/del displayed a competitive transplantation advantage in primary or secondary recipient mice. These results demonstrate the consequences of heterozygous and homozygous CALR mutations and provide a powerful model for dissecting the pathogenesis of CALR-mutant ET and PMF

Targeting early changes in the synovial microenvironment:a new class of immunomodulatory therapy?

Objectives: Controlled immune responses rely on integrated crosstalk between cells and their microenvironment. We investigated whether targeting proinflammatory signals from the extracellular matrix that persist during pathological inflammation provides a viable strategy to treat rheumatoid arthritis (RA). Methods: Monoclonal antibodies recognising the fibrinogen-like globe (FBG) of tenascin-C were generated by phage display. Clones that neutralised FBG activation of toll-like receptor 4 (TLR4), without impacting pathogenic TLR4 activation, were epitope mapped by crystallography. Antibodies stained synovial biopsies of patients at different stages of RA development. Antibody efficacy in preventing RA synovial cell cytokine release, and in modulating collagen-induced arthritis in rats, was assessed. Results: Tenascin-C is expressed early in the development of RA, even before disease diagnosis, with higher levels in the joints of people with synovitis who eventually developed RA than in people whose synovitis spontaneously resolved. Anti-FBG antibodies inhibited cytokine release by RA synovial cells and prevented disease progression and tissue destruction during collagen-induced arthritis. Conclusions: Early changes in the synovial microenvironment contribute to RA progression; blocking proinflammatory signals from the matrix can ameliorate experimental arthritis. These data highlight a new drug class that could offer early, disease-specific immune modulation in RA, without engendering global immune suppression