Multi-objective optimization of turbocharger turbines for low carbon vehicles using meanline and neural network models

Due to slow turnover of the global vehicle parc internal combustion engines will remain a primary means of motive power for decades, so the automotive industry must continue to improve engine thermal efficiency to reduce emissions, since savings will be compounded over the long lifetime of millions of vehicles. Turbochargers are a proven efficiency technology (most new vehicles are turbocharged) but are not optimally designed for real-world driving. The aim of this study was to develop a framework to optimize turbocharger turbine design for competing customer objectives: minimizing fuel consumption (and thus emissions) over a representative drive cycle, while minimizing transient response time. This is achieved by coupling engine cycle, turbine meanline, and neural network inertia models within a genetic algorithm-based optimizer, allowing aerodynamic and inertia changes to be accurately reflected in drive cycle fuel consumption and transient performance. Exercising the framework for the average new passenger car across a drive cycle representing the Worldwide harmonized Light vehicles Test Procedure reveals the trade-off between competing objectives and a turbine design that maintains transient response while minimizing fuel consumption due to a 3 percentage-point improvement in turbine peak efficiency, validated by experiment. This optimization framework is fast to execute, requiring only eight turbine geometric parameters, making it a commercially viable procedure that can refine existing or optimize tailor-made turbines for any turbocharged application (whether gasoline, diesel, or alternatively fuelled), but if applied to turbocharged gasoline cars in the EU would lead to lifetime savings of 290,000 tonnes per production year, and millions of tonnes if deployed worldwide

Myocardial revascularization by left ventricular assisted beating heart is associated with reduced systemic inflammatory response

BACKGROUND: The present study was designed to investigate whether use of left ventricular assisted technique (LVA) in beating-heart myocardial revascularization would exert less impact on patients' inflammatory response, as compared with minimal extracorporeal circulation (MECC). METHODS: Seventy-three consecutive high-risk patients undergoing myocardial revascularization were randomly assigned either to LVA (group A) or to MECC (group B). Monocyte count and plasma concentration of C-reactive protein, inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha, and polymorphonuclear elastase were measured at baseline and at various time points postoperatively. RESULTS: Preoperative clinical and demographic data did not differ between the two groups. The two groups also were similar with respect to mortality, number of grafts performed, duration of extracorporeal circulation, and need for inotropes. However, LVA was associated with significantly less inflammatory response postoperatively compared with MECC, as indicated by a significant difference in interleukin-6 (p = 0.002), C-reactive protein (p = 0.002), monocyte percentage (p = 0.006), tumor necrosis factor-alpha (p = 0.002), and polymorphonuclear elastase (p = 0.001). CONCLUSIONS: High-risk patients undergoing beating-heart myocardial revascularization with LVA show reduced inflammatory response compared with patients treated with the MECC

Selective activation of anti-CD73 mechanisms in control of primary tumors and metastases

The emerging role for CD73 in driving cancer growth and metastasis has presented opportunities to develop anti-CD73 monoclonal antibodies (mAbs) in the treatment of human cancers. Blockade of CD73 by antagonistic CD73 mAbs ameliorates tumor growth and metastasis via the inhibition of enzymatic and non-enzymatic CD73 pathways. In this study, we investigated whether Fc-receptor cross-linking represented a non-redundant mechanism by which anti-CD73 mAbs exert potent suppression of solid tumors and metastases. We engineered four anti-CD73 mAbs, each different in their ability to modulate CD73 enzymatic function and bind Fc receptors. mAbs recognizing a similar epitope of CD73 (CD73–04, TY/23 and 2C5) displayed the greatest antitumor activity. Importantly, we observed that the optimal control of metastasis by anti-CD73 mAbs involved primarily Fc receptor engagement, while suppression of solid tumors required both, enzyme inhibition and activation of Fc receptors. Engagement of Fc-receptors was also essential for optimal anti-metastatic effect in combination with either A2AR inhibitor or anti-PD-1 mAb treatment. The control of experimental metastases relied on the activation of host NK cells and IFNγ, while NK cells, CD8 T cells and IFNγ were needed for effective antitumor effect in the spontaneous metastases model. These observations advance our understanding of the enzymatic and non-enzymatic functions of anti-CD73 mAbs in solid tumors and metastases. Altogether, these findings will greatly assist in the design of anti-CD73 mAbs to be used as either single agents or in combination with other immunotherapeutic molecules or targeted therapies

Thrombocytopenia Complicating Transcatheter Aortic Valve Implantation: Differences Between Two New-Generation Devices

Thrombocytopenia after TAVI is common and clinically detrimental. Retrospectively, we observed Portico recipients had a more profound platelet drop than Evolut recipients. We thus investigated periprocedural platelet damage and/orpro-inflammatory state in 64 TAVI recipients at baseline and after implantation. Platelet damage was assessed by annexin V staining and monocyte-phagocytic phenotype was assessed according to CD14/CD36 expression. Serum cytokines were measured in 20 patients. The formaldehyde-based storage solution altered platelets. When, before being loaded onto the delivery system, Portico underwent one additional flushing to those recommended, the receiving patients showed thrombocytopenia, platelet damage, and CD36-monocyte count were mitigated. A general increase in IL-6 was recorded in overall TAVI recipients, but a high serum level of IL-8, a potent thrombocytopenia inducer, was measured in Portico recipients only, including those with extra-rinsed valve. Our study suggests a platelet-injury effect by storage-solution and generates the hypothesis of a role for the biomaterial in stimulating innate-immunity. Larger prospective studies are needed. [Figure not available: see fulltext.

Identification and engineering of human variable regions that allow expression of stable single-chain T cell receptors

Single-chain antibody fragments (scFv), consisting of two linked variable regions (VH and VL), are a versatile format for engineering and as potential antigen-specific therapeutics. Although the analogous format for T cell receptors (TCRs), consisting of two linked V regions (Vα and Vβ; referred to here as scTv), could provide similar opportunities, all wild-type scTv proteins examined to date are unstable. This obstacle has prevented scTv fragments from being widely used for engineering or therapeutics. To further explore whether some stable human scTv fragments could be expressed, we used a yeast system in which display of properly folded domains correlates with ability to express the folded scTv in soluble form. We discovered that, unexpectedly, scTv fragments that contained the human Vα2 region (IMGT: TRAV12 family) were displayed and properly associated with different Vβ regions. Furthermore, a single polymorphic residue (Serα49) in the framework region conferred additional thermal stability. These stabilized Vα2-containing scTv fragments could be expressed at high levels in Escherichia coli, and used to stain target cells that expressed the specific pep-HLA-A2 complexes. Thus, the scTv fragments can serve as a platform for engineering TCRs with diverse specificities, and possibly for therapeutic or diagnostic applications