Previous studies suggest that membrane lipids may regulate proteolytic processing of the amyloid precursor protein (APP) to generate amyloid-beta peptide (Abeta). In the present study, we have assessed the capacity for a series of structurally related synthetic ceramide analogues to modulate APP processing in vitro.
The compounds tested are established glucosylceramide synthase (GS) inhibitors based on the d -1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) structure. PDMP and related compounds PPMP and EtDO-P4 inhibited Abeta secretion from Chinese hamster ovary cells expressing human APP (CHO-APP) with approximate IC 50 values of 15, 5, and 1μM, respectively. A trend for reduced secretion of the APP alpha-secretase product, sAPPalpha, was also observed in… PDMP-treated cells but not in PPMP- or ETDO-P4-treated cells, whereas levels of the cellular beta-secretase product APP C-terminal fragment, CTFbeta, were increased by both PDMP and PPMP but unaltered with EtDO-P4 treatment.
Our data also revealed that EtDO-P4 inhibits endogenous Abeta production by human neurons. In conclusion, this study provides novel information regarding the regulation of APP processing by synthetic ceramide analogues and reveals that the most potent of these compounds is EtDO-P4.
Shared buffer switches consist of a memory pool completely shared among output ports of a switch. Shared buffer switches achieve low packet loss performance as buffer space is allocated in a flexible manner. However, this type of buffered switches suffers from high packet losses when the input traffic is imbalanced and bursty. Heavily loaded output ports dominate the usage of shared memory and lightly loaded ports cannot have access to these buffers.
To regulate the lengths of very active queues and avoid performance degradations, threshold‐based dynamic buffer management policy, decay function threshold, is proposed in this paper. Decay function threshold is a per‐queue threshold scheme that uses a tailored threshold for each output port queue. This scheme… suggests that buffer space occupied by an output port decays as the queue size of this port increases and/or empty buffer space decreases.
Results have shown that decay function threshold policy is as good as well‐known dynamic thresholds scheme, and more robust when multicast traffic is used. The main advantage of using this policy is that besides best‐effort traffic it provides support to quality of service (QoS) traffic by using an integrated buffer management and scheduling framework. Copyright © 2006 John Wiley & Sons, Ltd.
Previous attempts to use goal setting and feedback to improve safety behaviour on construction sites have focused on operatives, but recognized management commitment as essential for success. This research addressed two problems: validly and reliably measuring the safety performance of construction managers; and motivating managers to improve their safety performance.
A measure of management safety performance was developed, covering seven items: induction training; toolbox talk training; safety committees; subcontractor safety; maintenance of safety records; safety manager actions and safety consideration (interaction, communication and worker engagement). This was used on a case study site to improve motivation of the management team. During an intervention, using monthly feedback and… goal-setting techniques, their performance improved from 49% to 82% of maximum expected performance.
The results demonstrate that a valid and reliable measure of management safety performance is practicable and support the proposition that goal setting can improve management safety performance in the construction industry.