The Influence of Swirl Brakes on the Rotordynamic Forces Generated by Discharge-to-Suction Leakage Flows in Centrifugal Pumps

Increasing interest has been give to swirl brakes as a means of reducing destabilizing rotordynamic forces due to leakage flows in new high speed rocket turbopumps. Although swirl brakes have been used successfully in practice (such as with the Space Shuttle HPOTP), no experimental test until now have been performed to demonstrate their beneficial effect over a range of leakage flow rates. The present study investigates the effect of swirl brakes on rotordynamic forces generated by discharge-to-suction leakage flows in the annulus of shrouded centrifugal pumps over a range of subsynchronous whirl ratios and various leakage flow rates. In addition, the effectiveness of swirl brakes in the presence of leakage inlet (pump discharge) swirl is also demonstrated. The experimental data demonstrates that with the addition of swirl brakes a significant reduction in the destabilizing tangential force for lower flow rates is achieved. At higher flow rates, the brakes are detrimental. In the presence of leakage inlet swirl, brakes were effective over all leakage flow rates tested in reducing the range of whirl frequency ratio for which the tangential force is destabilizing

Orthogonal Synthesis of Indolines and Isoquinolines via Aryne Annulation

Described in this report is the development of two unique methodologies exploiting the reactivity of arynes. Reaction of N-carbamoyl-functionalized enamine derivatives with benzyne affords substituted indolines. An orthogonal reactivity is uncovered when related enamine derivatives are modified as amides, such that isoquinolines are formed as the product of condensation with benzyne. This latter transformation is applied to a concise total synthesis of the opiate alkaloid papaverine

Feasibility study of a randomised controlled trial to investigate the treatment of sarcoidosis-associated fatigue with methylphenidate (FaST-MP): a study protocol

Introduction: Fatigue is a frequent and troublesome manifestation of chronic sarcoidosis. This symptom can be debilitating and difficult to treat, with poor response to the treatment. Symptomatic management with neurostimulants, such as methylphenidate, is a possible treatment option. The use of such treatment strategies is not without precedent and has been trialled in cancer-related fatigue. Their use in sarcoidosis requires further evaluation before it can be recommended for clinical practice. Methods and analysis: The Fatigue and Sarcoidosis—Treatment with Methylphenidate study is a randomised, controlled, parallel-arm and feasibility trial of methylphenidate for the treatment of sarcoidosis-associated fatigue. Patients are eligible if they have a diagnosis of sarcoidosis, significant fatigue (measured using the Fatigue Assessment Scale) and have stable disease. Up to 30 participants will be randomly assigned to either methylphenidate (20 mg two times per day) or identical placebo in a 3:2 ratio for 24 weeks. The primary objective is to collect data determining the feasibility of a future study powered to determine the clinical efficacy of methylphenidate for sarcoidosis-associated fatigue. The trial is presently open and will continue until July 2018. Ethics and dissemination: Ethical approval for the study was granted by the Cambridge Central Research Ethics Committee on 21 June 2016 (reference 16/EE/0087) and was approved and sponsored by the Norfolk and Norwich University Hospital (reference 190280). Clinical Trial Authorisation (EudraCT number 2016-000342-60) from the Medicines and Healthcare products Regulatory Agency (MHRA) was granted on 19 April 2016. Results will be presented at relevant conferences and submitted to appropriate journals following trial closure and analysis

Cross-Presentation of a Spread-Defective MCMV Is Sufficient to Prime the Majority of Virus-Specific CD8+ T Cells

CD8+ T cells can be primed by peptides derived from endogenous proteins (direct presentation), or exogenously acquired protein (cross-presentation). However, the relative ability of these two pathways to prime CD8+ T cells during a viral infection remains controversial. Cytomegaloviruses (CMVs) can infect professional antigen presenting cells (APCs), including dendritic cells, thus providing peptides for direct presentation. However, the viral immune evasion genes profoundly impair recognition of infected cells by CD8+ T cells. Nevertheless, CMV infection elicits a very strong CD8+ T cell response, prompting its recent use as a vaccine vector. We have shown previously that deleting the immune evasion genes from murine cytomegalovirus (MCMV) that target class I MHC presentation, has no impact on the size or breadth of the CD8+ T cell response elicited by infection, suggesting that the majority of MCMV-specific CD8+ T cells in vivo are not directly primed by infected professional APCs. Here we use a novel spread-defective mutant of MCMV, lacking the essential glycoprotein gL, to show that cross-presentation alone can account for the majority of MCMV-specific CD8+ T cell responses to the virus. Our data support the conclusion that cross-presentation is the primary mode of antigen presentation by which CD8+ T cells are primed during MCMV infection

Benzannulated Bicycles by Three-Component Aryne Reactions

Triple crown: A pair of three-component coupling reactions between arynes, isocyanides, and either activated alkynes or phenyl esters generates unusual iminoindenones or phenoxy iminoisobenzofurans (see scheme), the latter of which may be advanced to o-ketobenzamides by performing direct hydrolysis. The synthetic utility of these compounds is demonstrated in a rapid preparation of substituted dibenzoketocaprolactams

A Polymorphism in the α4 Nicotinic Receptor Gene (Chrna4) Modulates Enhancement of Nicotinic Receptor Function by Ethanol

Several studies indicate that ethanol enhances the activity of α4β2 nicotinic acetylcholine receptors (nAChR). Our laboratory has identified a polymorphism in the α4 gene that results in the substitution of an alanine (A) for threonine (T) at amino acid position 529 in the second intracellular loop of the α4 protein. Mouse strains expressing the A variant have, in general, greater nAChR-mediated 86 Rb + efflux in response to nicotine than strains with the T variant. However, the possibility of the polymorphism modulating the effects of ethanol on the 86 Rb + efflux response has not been investigated. Methods : We have used the 86 Rb + efflux method to study the acute effects of ethanol on the function of the α4β2 nAChR in the thalamus in six different mouse strains. Experiments were also performed on tissue samples taken from F2 intercross animals. The F2 animals were derived from A/J mice crossed with a substrain of C57BL/6J mice that carried a null mutation for the gene encoding the β2 nAChR subunit. Results : In strains carrying the A polymorphism (A/J, AKR/J, C3H/Ibg), coapplication of ethanol (10–100 mM) with nicotine (0.03–300 μM) increased maximal ion flux when compared with nicotine alone with no effect on agonist potency. In contrast, ethanol had little effect on the nicotine concentration-response curve in tissue prepared from strains carrying the T polymorphism (Balb/Ibg, C57BL/6J, C58/J). Experiments with the F2 hybrids demonstrated that one copy of the A polymorphism was sufficient to produce a significant enhancement of nAChR function by ethanol (50 mM) in animals that were also β2 +/+. Ethanol had no effect on nicotine concentration-response curves in T/T β2 +/+ animals. Conclusions : The results suggest that the A/T polymorphism influences the initial sensitivity of the α4β2 nAChR to ethanol.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65432/1/01.ALC.0000067973.41153.BC.pd