Retardation of Fatigue Crack Growth in Rotating Bending Specimens with Semi-Elliptical Cracks

This work investigates overload-induced retardation effects for semi-elliptically cracked steel round bars. The specimen geometry equals the shaft area of a 1:3 down-scaled railway axle and the material is extracted from railway axle blanks made of EA4T steel. Rotating bending tests under constant amplitude loading as well as overload tests considering overload ratios of ROL = 2.0 and ROL = 2.5 are conducted. The experimental results are compared to a crack growth assessment based on a modified NASGRO equation as well as the retardation model by Willenborg, Gallagher, and Hughes. The evaluated delay cycle number due to the overload by the experiments and the model shows a sound agreement validating the applicability of the presented approach.

Signal Timing Optimization Based on Fuzzy Compromise Programming for Isolated Signalized Intersection

In order to optimize the signal timing for isolated intersection, a new method based on fuzzy programming approach is proposed in this paper. Considering the whole operation efficiency of the intersection comprehensively, traffic capacity, vehicle cycle delay, cycle stops, and exhaust emission are chosen as optimization goals to establish a multiobjective function first. Then fuzzy compromise programming approach is employed to give different weight coefficients to various optimization objectives for different traffic flow ratios states. And then the multiobjective function is converted to a single objective function. By using genetic algorithm, the optimized signal cycle and effective green time can be obtained. Finally, the performance of the traditional method and new method proposed in this paper is compared and analyzed through VISSIM software. It can be concluded that the signal timing optimized in this paper can effectively reduce vehicle delays and stops, which can improve traffic capacity of the intersection as well.

An Investigation on the Effects of Subnet Extension on Delay and Throughput in Network-on-Chip

When designing a system-on-chip (SOC), a network-on-chip (NOC) paradigm is the backbone of used interconnection, but in recent years, with a great improvement in silicon technology and the ability to implement billions of transistors on a wafer, it sounds that wire-based communication is not efficient any longer, therefore designers intend to replace wireless transferring data methodology instead. In the following, we show how the performance of the wireless network is improved with subnet extension. This paper focuses on the evaluation of delay and throughput which are two important factors in network proficiency. In fact, to enhance the performance of the system, we need to reduce the number of delay cycles and improve the throughput, therefore to keep balance between these two parameters, designer has to adjust the packet injection rate (PIR) in a safe margin such that it does not exceed a certain point in each state, otherwise delay is uncontrollable, thus it is required to clearly identify the take-off points. About the designer also has to be informed purpose for which the system is going to be designed. It strictly depends on whether high throughput or low delay cycle is desirable. Subnet extension is a way to achieve this target. Here, totally three networks with the number of cores 64, 512 and 1024 have been selected, respectively. The effect of subnet extension is evaluated on each one. The behavior of each network with different number of subnets and IPs is studied. Obtained results from the simulator for different ranges of PIR and subnets are significant. To emphasize, we highlight the take-off points for the delay cycles and the points which does not cross the PIR level. Performance evaluation is conducted based on flit-accurate and open source system C simulator BookSim.

Researches on Design and Implementations of Two 2-Bit Predictors

High-performance superscalar processors, which can be used in building base-stations of cell phones and cloud-based web servers, rely heavily on aggressive branch predictors to avoid stalls no matter the branch is taken or not. Dynamic branch predictor which is based on the historical records of the previously executed branches always outputs good performance. Two-bit predictor discussed in this paper is one of the most popular ones that always practically employed. This paper demonstrates two implementations of two-bit predictors. Using BTB to process solo conditional branches is the first one, which is normally used. Other categories of branch instructions may results in several bubbles as the penalty. While the other implementation employs BTB dealing with all kinds of branch instructions, generating target addresses without any delay cycle. Simulation results show that the second implementation has much better performance than the former one. It decreases the mis-prediction rate from 12.26% to 11.48%, and also has much higher prediction accuracy on indirect jumps. With these results, we have our predictor re-designed accordingly and implemented successfully in superscalar processors.

A phase I trial of weekly combination KOS-862 (Epothilone D) and trastuzumab in HER-2 overexpressing malignancies

2028 Background: KOS-862 (Epothilone D) (K) has shown single agent activity against metastatic breast cancer (MBC) and NSCLC. Trastuzumab (H) is standard therapy for HER-2 overexpressing MBC. This phase IB trial determined the safety and PK profile of KOS-862 in a weekly schedule with H. Methods: Eligibility: pts with HER-2 overexpressing (IHC 3+ or FISH +) chemo-refractory tumors, ECOG ≤ 2, neuropathy ≤ gr 1, no CNS metastases, and no H ≤ 6 mo. prestudy. H given as a 4 mg/kg loading dose, then 2 mg/kg wkly. K given as a 90 min iv infusion wkly × 3 Q 4 wks after H. K dose escalation cohorts: 70, 85 & 100 mg/m2. H1 + H2 antagonists + corticosteroid prophylaxis given 30–60 min prior to K. DLT: gr 4 hematologic or gr 3 other toxicity, or toxicity requiring >4 wk treatment delay. Cycle 1 + 2 PK samples obtained for K + H. Results: 13 pts treated from 9/04 - 8/05. Median age 51 yrs (36–65). All pts had MBC. Prior H therapy n = 9, prior taxane n = 11. Enrollment: 70 mg/m2 (4), 85 mg/m2 (3), and 100 mg/m2 (6). Mean number cycles 3.9 (1–6). The 100 mg/m2 cohort was expanded to 6 pts per study design; no DLTs were noted. Toxicity: Principal neurotoxicities (gr 3 noted, if present): parasthesias (10 pts, 1 gr3), neuropathic pain (5 pts, 2 gr3), dizziness (4 pts), dysguesia (4 pts), ataxia (3 pts), transient confusion (3 pts), dysesthesias (2 pts), insomnia (2 pts). No gr 4 neurotoxicities reported. Non-neurologic toxicities were limited to gr 1/2 and included diarrhea, pyrexia, abdominal and back pain, arthralgias. PK (n = 13): KOS-862 CL 21 ± 10 L/hr, Vz 260 ± 110 L, T1/2 9.8 ± 3.9 hr. Seco-metabolite was 67% ± 35% of K. At 100 mg/m2 K dose (n = 6): Cmax 3.3 ± 1.1 μg/mL and AUCinf 11.0 ± 7.5 h*(g/mL). Neither K nor its seco-metabolite PK were affected by H. Responses: An 85 mg/m2 K pt (no prior H or taxane) had confirmed PR and a 100 mg/m2 K pt (prior taxane) had an unconfirmed PR. A 2nd 100 mg/m2 pt (no prior H or taxane, bone only disease) had > 90% CEA reduction. Conclusions: This phase I study demonstrates feasibility of full dose wkly KOS-862 coadministration with wkly H. Treatment-related toxicities were all gr 1 / 2, except for 3 cases gr 3 paresthesias and neuropathic pain. PK of K and its principal metabolite were not affected by H. Three clinical responses were observed; a phase II trial of this combination is ongoing in minimally-pretreated MBC. [Table: see text]