Cardiac safety of adjuvant pegylated liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial

Background The cardiac safety of trastuzumab concurrent with pegylated liposomal doxorubicin (PLD) in an adjuvant breast cancer treatment regimen is unknown. Patients and methods Women with resected node-positive or intermediate-risk node-negative HER2 overexpressing breast cancer and baseline left ventricular ejection fraction (LVEF) ≥55% were randomized (1:2) to doxorubicin 60 mg/m2 (A)+cyclophosphamide 600 mg/m2 (C) every 21 days (q21d) for four cycles or PLD 35 mg/m2+C q21d+trastuzumab 2 mg/kg weekly (H) for 12 weeks. Both groups then received paclitaxel (Taxol, T) 80 mg/m2 with H for 12 weeks followed by H to complete 1 year. The primary end point was cardiac event rate or inability to administer 1 year of trastuzumab. Results Of 181 randomized patients, 179 underwent cardiac analysis. The incidence of cardiac toxicity or inability to administer trastuzumab due to cardiotoxicity was 18.6% [n=11; 95% confidence interval (CI) 9.7% to 30.9%] with A+C → T+H and 4.2% (n=5; 95% CI 1.4% to 9.5%) with PLD+C+H → T+H (P=0.0036). All events, except one, were asymptomatic systolic dysfunction or mildly symptomatic heart failure. Mean absolute LVEF reduction at cycle 8 was greater with doxorubicin (5.6% versus 2.1%; P=0.0014). Conclusion PLD+C+H → T+H is feasible and results in lower early cardiotoxicity rates compared with A+C → T+

Software diversity for improved network security: optimal distribution of software-based shared vulnerabilities

Due to copyright restrictions, the access to the full text of this article is only available via subscription.Firms, and other agencies, tend to adopt widely used software to gain economic benefits of scale, which can lead to a software monoculture. This can, in turn, involve the risk of correlated computer systems failure as all systems on the network are exposed to the same software-based vulnerabilities. Software diversity has been introduced as a strategy for disrupting such a monoculture and ultimately decreasing the risk of correlated failure. Nevertheless, common vulnerabilities can be shared by different software products. We thus expand software diversity research here and consider shared vulnerabilities between different software alternatives. We develop a combinatorial optimization model of software diversity on a network in an effort to identify the optimal software distribution that best improves network security. We also develop a simulation model of virus propagation based on the susceptible-infected-susceptible model. This model allows calculation of the epidemic threshold, a measure of network resilience to virus propagation. We then test the effectiveness of the proposed software diversity strategies against the spreading of viruses through a series of experiments.Belk College Summer Research Gran

Color Doppler analysis of female reproductive vasculature in Behçet’s disease

Behçet’s disease (BD) may affect female reproductive vasculature. We aimed to evaluate Doppler sonographic characteristics of female reproductive vasculature and also ovarian volume, endometrial thickness (EMT) and antral follicle count of BD patients in comparison with a healthy control group. Seventeen premenopausal women aged between 18-45 years with BD, and a control group of 31 age- and body mass index-matched healthy women was included in the study. Uterine, spiral and intraovarian artery blood flow were examined by Doppler sonography in the late follicular phase. Resistance index, pulsatility index and systolic/diastolic ratio were recorded together with ovarian volume, EMT and antral follicle count. In particular this is a pilot study including the evaluation of the spiral and uterine arteries in BD. Doppler sonographic parameters, ovarian volume, EMT and antral follicle count of BD patients and healthy controls were not found to be statistically different. As a result of our analysis, we found similar Doppler sonographic features of both BD patients and the control group. Further studies conducted on a larger sample population with more aggressive BD symptoms may reveal the actual effect of BD on the female reproductive system

Isolation and characterization of glucose derepressed invertase mutants from Schizosaccharomyces pombe

We have isolated 14 different Schizosaccharontyces pombe mutants that synthesize invertase enzyme constitutively. Analyses of invertase activities revealed that the degrees of resistance to glucose repression were not similar among different complementation groups. One of the complementation groups appeared to be associated with functional and/or regulatory defects in hexose transport. Another complementation group appeared to be specific for the regulation of the inv1 gene alone, implying that these mutations might be associated with different genes acting on the glucose sensing and signaling pathway. In addition, we found that the wild-type level glucose uptake is essential for the full-level repression of inv1 expression

Generating fast logic circuits for m-select n-port round Robin arbitration

Due to copyright restrictions, the access to the full text of this article is only available via subscription.This paper generalizes the problem of Round Robin Arbitration (RRA) from 1-select to m-select (mRRA) and offers new circuit architectures for it. RRAs are found in networking equipment and computer systems with high throughput buses. We first propose fast/novel circuits for the fundamental problem of finding the first m 1's in an n-bit vector (from the left or right), i.e., generalized select Priority Encoder (mPE). The obvious solution to mPE is cascading m regular (1-select) PEs. Our solutions, however, are based on parallel prefix networks, where the nodes are replaced by "saturated adder"s. We use mPE as a building block to construct an mRRA, which has single cycle latency and can arbitrate up to m requests per clock cycle. We took two arbiters from the liter rature, TC-PPA (1-select) and 3DP2S (2-select), and generalized them into mRRAs, which we call mTC-PPA and 3DPmS-RRA. We wrote fully parameterized HDL code generators. Logic synthesis results show that mTC-PPA and 3DPmS-RRA are up to 100% faster than the cascade solution and have up to 65% smaller Area-Timing Products (ATP). Comparing mTC-PPA and 3DPmS-RRA, 3DPmS-RRA circuits are slightly faster than mTC-PPA on the average. In terms of ATP, mTC-PPA is superior by far and can be as small as 30% of 3DPmS-RRA

Effects of temperature — heavy metal interactions, antioxidant enzyme activity and gene expression in wheat (Triticum aestivum L.) seedlings

In this study, the effect of heat and chromium (Cr) heavy metal interactions on wheat seedlings (Triticum aestivum L. cv. Ç-1252 and Gun91) was investigated by measuring total chlorophyll and carotenoid levels, catalase (CAT) and ascorbate peroxidase (APX) antioxidant enzyme activities, and MYB73, ERF1 and TaSRG gene expression. Examination of pigment levels demonstrated a decrease in total chlorophyll in both species of wheat under combined heat and heavy metal stress, while the carotenoid levels showed a slight increase. APX activity increased in both species in response to heavy metal stress, but the increase in APX activity in the Gun91 seedlings was higher than that in the Ç-1252 seedlings. CAT activity increased in Gun91 seedlings but decreased in Ç-1252 seedlings. These results showed that Gun91 seedling had higher resistance to Cr and Cr + heat stresses than the Ç-1252 seedling. The quantitative molecular analyses implied that the higher resistance was related to the overexpression of TaMYB73, TaERF1 and TaSRG transcription factors. The increase in the expression levels of these transcription factors was profound under combined Cr and heat stress. This study suggests that TaMYB73, TaERF1 and TaSRG transcription factors regulate Cr and heat stress responsive genes in wheat

A rapid technique for the determination of furfural in the fission yeast culture media

A simple and rapid technique for the determination of furfural in the culture medium, which contains this compound as a degradation product of xylose at autoclave conditions, was evaluated. Besides, the growth and the furfural metabolism of the fission yeast Schizosaccharomyces pombe has been monitored using spectral methods