113 research outputs found
Solidification and processing of aluminium based immiscible alloys
Copyright @ 2009 TMSThe Al-Sn and Al-Pb based immiscible alloys have significant potential for bearing applications. However, the mixing and understanding of solidification process for immiscible alloys have been long standing challenges for their development. This paper presents solidification and microstructural evolution of the Al-Sn-Cu alloys and also describes the mechanism of effective mixing by the intensive shearing. The experimental work was also focused on analyzing the effects of shear rate, temperature and time on Sn droplets size and their distribution. Results have been compared with earlier study on Al-Si-Pb alloys. Experimental results suggest that the intensive shearing process produces homogeneous and finely dispersed Sn and Pb droplets.This work was funded by the EPSRC and DTI
The PPARγ Agonist Pioglitazone Fails to Alter the Abuse Potential of Heroin, But Does Reduce Heroin Craving and Anxiety
Possibly through its effects on glia, the peroxisome proliferator-activated gamma receptor (PPARγ) agonist pioglitazone (PIO) has been shown to alter the effects of heroin in preclinical models. Until now, these results have not been assessed in humans. Heroin-dependent participants were randomized to either active (45 mg, n = 14) or placebo (0 mg, n = 16) PIO maintenance for the duration of the three-week study. After stabilization on buprenorphine (8 mg), participants began a two-week testing period. On the first to fourth test days, participants could self-administer drug or money by making verbal choices for either option. On the fifth day, active heroin and money were administered and participants could work to receive heroin or money using a progressive ratio choice procedure. Test days 6–10 were identical to test days 1–5 with the exception that, during one of the test weeks, placebo was available on the first four days, and during the other week heroin was available. PIO failed to alter the reinforcing or positive subjective effects of heroin, but it did reduce heroin craving and overall anxiety. Although we were unable to replicate the robust effects found in preclinical models, these data provide an indication of drug effects that deserves further exploration
Solidification of Al-Sn-Cu based immiscible alloys under intense shearing
The official published version of the Article can be accessed from the link below - Copyright @ 2009 The Minerals, Metals & Materials Society and ASM InternationalThe growing importance of Al-Sn based alloys as materials for engineering applications
necessitates the development of uniform microstructures with improved performance. Guided by the recently thermodynamically assessed Al-Sn-Cu system, two model immiscible alloys, Al-45Sn-10Cu and Al-20Sn-10Cu, were selected to investigate the effects of intensive melt shearing provided by the novel melt conditioning by advanced shear technology (MCAST) unit on the uniform dispersion of the soft Sn phase in a hard Al matrix. Our experimental results have confirmed that intensive melt shearing is an effective way to achieve fine and uniform
dispersion of the soft phase without macro-demixing, and that such dispersed microstructure can be further refined in alloys with precipitation of the primary Al phase prior to the demixing reaction. In addition, it was found that melt shearing at 200 rpm and 60 seconds will be adequate to produce fine and uniform dispersion of the Sn phase, and that higher shearing speed and prolonged shearing time can only achieve minor further refinement.This work is funded by the EPSRC and
DT
Exploration of a Potential DOOR Endpoint for Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia Using Six Registrational Trials for Antibacterial Drugs
BACKGROUND: Desirability of outcome ranking (DOOR) is an innovative approach to clinical trial design and analysis that uses an ordinal ranking system to incorporate the overall risks and benefits of a therapeutic intervention into a single measurement. Here we derived and evaluated a disease-specific DOOR endpoint for registrational trials for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP).
METHODS: Through comprehensive examination of data from nearly 4000 participants enrolled in six registrational trials for HABP/VABP submitted to the Food and Drug Administration (FDA) between 2005 and 2022, we derived and applied a HABP/VABP specific endpoint. We estimated the probability that a participant assigned to the study treatment arm would have a more favorable overall DOOR or component outcome than a participant assigned to comparator.
RESULTS: DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 48.3% to 52.9% and were not statistically different. There were no significant differences between treatment arms in the component analyses. Although infectious complications and serious adverse events occurred more frequently in ventilated participants compared to non-ventilated participants, the types of events were similar.
CONCLUSIONS: Through a data-driven approach, we constructed and applied a potential DOOR endpoint for HABP/VABP trials. The inclusion of syndrome-specific events may help to better delineate and evaluate participant experiences and outcomes in future HABP/VABP trials and could help inform data collection and trial design
Targeted Manipulation of Serotonergic Neurotransmission Affects the Escalation of Aggression in Adult Male Drosophila melanogaster
Dopamine (DA) and serotonin (5HT) are reported to serve important roles in aggression in a wide variety of animals. Previous investigations of 5HT function in adult Drosophila behavior have relied on pharmacological manipulations, or on combinations of genetic tools that simultaneously target both DA and 5HT neurons. Here, we generated a transgenic line that allows selective, direct manipulation of serotonergic neurons and asked whether DA and 5HT have separable effects on aggression. Quantitative morphological examination demonstrated that our newly generated tryptophan hydroxylase (TRH)-Gal4 driver line was highly selective for 5HT-containing neurons. This line was used in conjunction with already available Gal4 driver lines that target DA or both DA and 5HT neurons to acutely alter the function of aminergic systems. First, we showed that acute impairment of DA and 5HT neurotransmission using expression of a temperature sensitive form of dynamin completely abolished mid- and high-level aggression. These flies did not escalate fights beyond brief low-intensity interactions and therefore did not yield dominance relationships. We showed next that manipulation of either 5HT or DA neurotransmission failed to duplicate this phenotype. Selective disruption of 5HT neurotransmission yielded flies that fought, but with reduced ability to escalate fights, leading to fewer dominance relationships. Acute activation of 5HT neurons using temperature sensitive dTrpA1 channel expression, in contrast, resulted in flies that escalated fights faster and that fought at higher intensities. Finally, acute disruption of DA neurotransmission produced hyperactive flies that moved faster than controls, and rarely engaged in any social interactions. By separately manipulating 5HT- and DA- neuron systems, we collected evidence demonstrating a direct role for 5HT in the escalation of aggression in Drosophila
ESOP\u27s and Market Distortions
Since 1974, Congress has created numerous tax benefits favoring Employee Stock Ownership Plans (ESOPs). Congress significantly expanded those benefits with the Deficit Reduction Act of1984, and as a result the use of ESOPs is likely to increase substantially in the future. In this Article, Professors Doernberg and Macey argue that ESOPs do not deliver the non-tax benefits claimed for them by proponents and cause inefficient market distortions. After exploring the history and requirements ofESOPs, they discuss various market distortions caused by ESOPs, with particular emphasis on the market for corporate control. After reviewing the treatment ESOPs have received in recent tax reform proposals, Professors Doernberg and Macey conclude by suggesting that many of the beneficial goals ESOPs are alleged to serve could be better achieved by modifying the laws governing individual retirement accounts
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