Active Control of an Axial Flow Compressor via Pulsed Air Injection

This paper presents the use of pulsed air injection to control the onset of rotating stall in a low-speed, axial flow compressor. By measuring the unsteady pressures near the rotor face, a control algorithm determines the magnitude and phase of the first mode of rotating stall and controls the injection of air in the front of the rotor face. Experimental results show that this technique slightly extends the stall point of the compressor and eliminates the hysteresis loop normally associated with rotating stall. A parametric study is used to determine the optimal control parameters for suppression of stall. Analytic results---using a low-dimensional model developed by Moore and Greitzer combined with an unsteady shift in the compressor characteristic to model the injectors---give further insights into the operation of the controller. Based on this model, we show that the behavior of the experiment can be explained as a change in the bifurcation behavior of the system under nonlinear feedback. A higher fidelity simulation model is then used to further verify some of the specific performance characteristics that are observed in experiments

Wolff-Parkinson-White syndrome in an adolescent with depression

Wolff-Parkinson-White (WPW) syndrome is a congenital disorder characterised by a macro-reentrant arrhythmia caused by preexcitation of the ventricles. A significant proportion of cases are detected incidentally in asymptomatic patients during routine checkups. Because little is known about the use of selective serotonin reuptake inhibitors in youths with preexisting cardiac disease, we report here a 15-year-old adolescent with asymptomatic WPW syndrome and severe depressive symptoms. An improvement in depressive symptoms was observed with sertraline therapy and the absence of cardiac adverse effects after 5 months of treatment suggested that sertraline could be used at therapeutic doses in adolescents with preexisting but asymptomatic WPW syndrome

Control of rotating stall in a low-speed axial flow compressor using pulsed air injection: modeling, simulations, and experimental validation

Previous results in the use of pulsed air injection for active control of rotating stall have suggested that air injectors have the effect of shifting the steady state compressor characteristic. In this paper we analyze the effect of a compressor characteristic actuation scheme for the three state Moore Greitzer compression system model. It is shown that closed loop feedback based on the square magnitude of the first rotating stall mode can be used to decrease the hysteresis region associated with the transition from unstalled to stalled and back to unstalled operation. The compressor characteristic shifting idea is then applied to a higher fidelity distributed model in which the characteristic shifting has phase content in addition to the magnitude content captured by the three state model. The optimal phasing of the air injection relative to the sensed position of the stall cell is determined via simulation and the results found to agree with those obtained via an experimental parametric study on the Caltech low-speed axial flow compressor

Type II Supernovae as Probes of Cosmology

- Constraining the cosmological parameters and understanding Dark Energy have tremendous implications for the nature of the Universe and its physical laws. - The pervasive limit of systematic uncertainties reached by cosmography based on Cepheids and Type Ia supernovae (SNe Ia) warrants a search for complementary approaches. - Type II SNe have been shown to offer such a path. Their distances can be well constrained by luminosity-based or geometric methods. Competing, complementary, and concerted efforts are underway, to explore and exploit those objects that are extremely well matched to next generation facilities. Spectroscopic follow-up will be enabled by space- based and 20-40 meter class telescopes. - Some systematic uncertainties of Type II SNe, such as reddening by dust and metallicity effects, are bound to be different from those of SNe Ia. Their stellar progenitors are known, promising better leverage on cosmic evolution. In addition, their rate - which closely tracks the ongoing star formation rate - is expected to rise significantly with look- back time, ensuring an adequate supply of distant examples. - These data will competitively constrain the dark energy equation of state, allow the determination of the Hubble constant to 5%, and promote our understanding of the processes involved in the last dramatic phases of massive stellar evolution.Comment: Science white paper, submitted to the Decadal committee Astro201

Preclinical toxicology and safety pharmacology of the first-in-class GADD45β/MKK7 inhibitor and clinical candidate, DTP3

Aberrant NF-κB activity drives oncogenesis and cell survival in multiple myeloma (MM) and many other cancers. However, despite an aggressive effort by the pharmaceutical industry over the past 30 years, no specific IκBα kinase (IKK)β/NF-κB inhibitor has been clinically approved, due to the multiple dose-limiting toxicities of conventional NF-κB-targeting drugs. To overcome this barrier to therapeutic NF-κB inhibition, we developed the first-in-class growth arrest and DNA-damage-inducible (GADD45)β/mitogen-activated protein kinase kinase (MKK)7 inhibitor, DTP3, which targets an essential, cancer-selective cell-survival module downstream of the NF-κB pathway. As a result, DTP3 specifically kills MM cells, ex vivo and in vivo, ablating MM xenografts in mice, with no apparent adverse effects, nor evident toxicity to healthy cells. Here, we report the results from the preclinical regulatory pharmacodynamic (PD), safety pharmacology, pharmacokinetic (PK), and toxicology programmes of DTP3, leading to the approval for clinical trials in oncology. These results demonstrate that DTP3 combines on-target-selective pharmacology, therapeutic anticancer efficacy, favourable drug-like properties, long plasma half-life and good bioavailability, with no target-organs of toxicity and no adverse effects preclusive of its clinical development in oncology, upon daily repeat-dose administration in both rodent and non-rodent species. Our study underscores the clinical potential of DTP3 as a conceptually novel candidate therapeutic selectively blocking NF-κB survival signalling in MM and potentially other NF-κB-driven cancers

CHK1 inhibition as a strategy for targeting fanconi anemia (FA) DNA repair pathway deficient tumors

<p>Abstract</p> <p>Background</p> <p>DNA repair deficient tumor cells have been shown to accumulate high levels of DNA damage. Consequently, these cells become hyper-dependent on DNA damage response pathways, including the CHK1-kinase-mediated response. These observations suggest that DNA repair deficient tumors should exhibit increased sensitivity to CHK1 inhibition. Here we offer experimental evidence in support of this hypothesis.</p> <p>Results</p> <p>Using isogenic pairs of cell lines differing only in the Fanconi Anemia (FA) DNA repair pathway, we showed that FA deficient cell lines were hypersensitive to <it>CHK1 </it>silencing by independent siRNAs as well as CHK1 pharmacologic inhibition by Gö6976 and UCN-01. In parallel, an siRNA screen designed to identify gene silencings synthetically lethal with CHK1 inhibition identified genes required for FA pathway function. To confirm these findings <it>in vivo</it>, we demonstrated that whole zebrafish embryos, depleted for <it>FANCD2 </it>by a morpholino approach, were hypersensitive to Gö6976. Silencing of FA genes led to hyper-activation of CHK1 and vice versa. Furthermore, inactivation of CHK1 in FA deficient cell lines caused increased accumulation of DNA strand and chromosomal breakages. These results suggest that the functions subserved by CHK1 and the FA pathway mutually compensate in maintaining genome integrity. As CHK1 inhibition has been under clinical trial in combination with cisplatin, we showed that the FA specific tumoricidal effect of CHK1 inhibition and cisplatin was synergistic.</p> <p>Conclusion</p> <p>Taken together, these results suggest CHK1 inhibition as a strategy for targeting FA deficient tumors.</p

Control of rotating stall in a low-speed axial flow compressor using pulsed air injection: modeling, simulations, and experimental validation

Previous results in the use of pulsed air injection for active control of rotating stall have suggested that air injectors have the effect of shifting the steady state compressor characteristic. In this paper we analyze the effect of a compressor characteristic actuation scheme for the three state Moore Greitzer compression system model. It is shown that closed loop feedback based on the square magnitude of the first rotating stall mode can be used to decrease the hysteresis region associated with the transition from unstalled to stalled and back to unstalled operation. The compressor characteristic shifting idea is then applied to a higher fidelity distributed model in which the characteristic shifting has phase content in addition to the magnitude content captured by the three state model. The optimal phasing of the air injection relative to the sensed position of the stall cell is determined via simulation and the results found to agree with those obtained via an experimental parametric study on the Caltech low-speed axial flow compressor