Flexible Timing Simulation of Multiple-Cache Configurations

Abstract As the gap between processor and memory speeds increases, cache performance becomes more critical to overall system performance. Behavioral cache simulation is typically used early in the design cycle of new processor/cache configurations to determine the performance of proposed cache configurations on target workloads. However, behavioral cache simulation does not account for the latency seen by each memory access. The Latency-Effects (LE) cache model presented in this paper accounts this nominal latency as well as the additional latencies due to trailing-edge effects, bus width considerations, port conflicts, and the number of outstanding accesses that a cache allows before it blocks. We also extend the LE cache model to handle the latency effects of moving data among multiple caches. mlcache, a new, easily configurable and extensible tool, has been built based on the extended LE model. We show the use of mlcache in estimating the performance of traditional and novel cache configurations, including odd/even, 2-level, Assist, Victim, and NTS caches. We also show how the LE cache timing model provides more useful, realistic performance estimates than other possible behavioral-level cache timing models. Keywords: cache timing simulation model evaluation Introduction Cache performance becomes ever more critical to overall system performance as the gap between processor and memory speed increases. The performance of a particular cache configuration depends not only on the miss ratio incurred during the execution of a particular workload but also on where in the program's execution the misses occur and the latency of each miss. However, useful timing simulation of caches is typically unavailable until late in the design stage. Using today's behavioral simulators, simple, traditional caches are evaluated early in the design cycle; however, novel cache designs are often not considered since they are difficult to model. The issue of providing more useful cache timing simulation analysis early in the design cycle has been addressed by the Latency-Effects (LE) cache model [Tam96], which incorporates latency-adding effects into a behavioral-level simulation, particularly trailing-edge effects, bus width considerations, the effects of port conflicts, and the number of outstanding accesses that a cache can handle before blocking. Existing methods of modifying behavioral cache simulators to incorporate timing effects include adjusting the total cycle count reported by a perfect cache simulation by adding an estimated number of cycles due to cache misses (the adjusted model) or assigning a nominal leading-edge penalty to each miss as it occurs (a model we will refer to as LEnominal). To illustrate the advantages of the LE cache model, we will compare the LE cache model's results to the results of using these other models. 1. This research was funded in part by a gift from IBM

The Role of Palliative Surgery for Malignant Bowel Obstruction and Perforation in Advanced Microsatellite Instability-High Colorectal Carcinoma in the Era of Immunotherapy: Case Report.

The role of palliative surgery in the management of acute complications in patients with disseminated malignancy remains controversial given the complexity of assessing acute surgical risk and long-term oncologic outcome. With the emergence of checkpoint blockade immunotherapy, there appears to be an increasing role for historically palliative procedures as a bridge to systemic immunotherapy. This is especially evident in advanced microsatellite instability-high (MSI-H) colorectal cancer where malignant obstruction and fistula formation are more common and where immunotherapy with checkpoint blockade (anti-PD-1/PD-L1, anti-CTLA-4) has a high response rate with potential for favorable oncologic outcomes. We present a series of three patients with MSI-H metastatic colorectal cancer complicated by malignant bowel obstruction and fistula formation, who having progressed on standard chemotherapy, underwent palliative intervention as a bridge to immune checkpoint blockade with durable and clinically meaningful anti-cancer responses. These cases highlight the need to re-evaluate the role of historically palliative operations in the setting of disease progression for immunotherapy-responsive tumors

An aeroacoustic investigation into the effect of self-oscillating trailing edge flaplets

The aeroacoustics of a NACA 0012 aerofoil with an array of self-oscillating flexible flaplets attached on the trailing edge has been investigated at low to moderate chord based Reynolds number (50,000 -- 350,000) and at geometric angles of attack from $\alpha_g = 0^\circ$ -- $20^\circ$. When the aerofoil is untripped, tonal peaks are observed on the baseline aerofoil. When the passive flaplets are attached to the pressure side of the aerofoil, the tonal peak is removed. If the flaplets are then placed on the suction side, the tonal peak is reduced, but not removed. It is therefore hypothesised that the flaplets on the pressure side modifies the laminar separation bubble situated on the pressure side of the aerofoil, a key mechanism for tonal noise. Throughout all cases, both tripped and untripped, a low frequency (0.1 kHz -- 0.6 kHz) noise reduction and a slight increase at higher frequencies (>2 kHz) is seen. This gives an average overall sound pressure level (OSPL) reduction of 1.5 -- 2 dB for the flaplets affixed to the pressure side. The cases where the tonal noise component is removed an OSPL reduction of up to 20 dB can be seen

Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair

Lysosomal enzyme acid sphingomyelinase is released extracellularly when cells are wounded, converting sphingomyelin to ceramide and inducing endosome formation to internalize membrane lesions

Directly observed antiretroviral therapy: a systematic review and meta-analysis of randomised clinical trials.

BACKGROUND: Directly observed therapy has been recommended to improve adherence for patients with HIV infection who are on highly active antiretroviral therapy, but the benefit and cost-effectiveness of this approach has not been established conclusively. We did a systematic review and meta-analysis of randomised trials of directly observed versus self-administered antiretroviral treatment. METHODS: We did duplicate searches of databases (from inception to July 27, 2009), searchable websites of major HIV conferences (up to July, 2009), and lay publications and websites (March-July, 2009) to identify randomised trials assessing directly observed therapy to promote adherence to antiretroviral therapy in adults. Our primary outcome was virological suppression at study completion. We calculated relative risks (95% CIs), and pooled estimates using a random-effects method. FINDINGS: 12 studies met our inclusion criteria; four of these were done in groups that were judged to be at high risk of poor adherence (drug users and homeless people). Ten studies reported on the primary outcome (n=1862 participants); we calculated a pooled relative risk of 1.04 (95% CI 0.91-1.20, p=0.55), and noted moderate heterogeneity between the studies (I(2)= 53.8%, 95% CI 0-75.7, p=0.0247) for directly observed versus self-administered treatment. INTERPRETATION: Directly observed antiretroviral therapy seems to offer no benefit over self-administered treatment, which calls into question the use of such an approach to support adherence in the general patient population. FUNDING: None

Global distribution and diversity of ovine-associated Staphylococcus aureus

Staphylococcus aureus is an important pathogen of many species, including sheep, and impacts on both human and animal health, animal welfare, and farm productivity. Here we present the widest global diversity study of ovine-associated S. aureus to date. We analysed 97 S. aureus isolates from sheep and sheep products from the UK, Turkey, France, Norway, Australia, Canada and the USA using multilocus sequence typing (MLST) and spa typing. These were compared with 196 sheep isolates from Europe (n = 153), Africa (n = 28), South America (n = 14) and Australia (n = 1); 172 bovine, 68 caprine and 433 human S. aureus profiles. Overall there were 59 STs and 87 spa types in the 293 ovine isolates; in the 97 new ovine isolates there were 22 STs and 37 spa types, including three novel MLST alleles, four novel STs and eight novel spa types. Three main CCs (CC133, CC522 and CC700) were detected in sheep and these contained 61% of all isolates. Four spa types (t002, t1534, t2678 and t3576) contained 31% of all isolates and were associated with CC5, CC522, CC133 and CC522 respectively. spa types were consistent with MLST CCs, only one spa type (t1403) was present in multiple CCs. The three main ovine CCs have different but overlapping patterns of geographical dissemination that appear to match the location and timing of sheep domestication and selection for meat and wool production. CC133, CC522 and CC700 remained ovine-associated following the inclusion of additional host species. Ovine isolates clustered separately from human and bovine isolates and those from sheep cheeses, but closely with caprine isolates. As with cattle isolates, patterns of clonal diversification of sheep isolates differ from humans, indicative of their relatively recent host-jump

Association Between Raised Blood Pressure and Dysglycemia in Hong Kong Chinese

OBJECTIVE—To investigate the association between raised blood pressure and dysglycemia