Cross-platform comparison of arbitrary quantum states.

As we approach the era of quantum advantage, when quantum computers (QCs) can outperform any classical computer on particular tasks, there remains the difficult challenge of how to validate their performance. While algorithmic success can be easily verified in some instances such as number factoring or oracular algorithms, these approaches only provide pass/fail information of executing specific tasks for a single QC. On the other hand, a comparison between different QCs preparing nominally the same arbitrary circuit provides an insight for generic validation: a quantum computation is only as valid as the agreement between the results produced on different QCs. Such an approach is also at the heart of evaluating metrological standards such as disparate atomic clocks. In this paper, we report a cross-platform QC comparison using randomized and correlated measurements that results in a wealth of information on the QC systems. We execute several quantum circuits on widely different physical QC platforms and analyze the cross-platform state fidelities.

Prevalence of overweight/obesity and fitness level in preschool children from the north compared with the south of Europe: an exploration with two countries.

BACKGROUND: North-south differences in the prevalence of obesity and fitness levels have been found in European adolescents, yet it is unknown if such differences already exist in very young children. OBJECTIVES: This study aims to compare the prevalence of overweight/obesity and fitness levels in preschool children aged 4 years from Sweden (north of Europe) and Spain (south of Europe). METHODS: The sample consisted of 315 Swedish and 128 Spanish preschoolers. Anthropometry (weight, height, waist circumference) and fitness (strength, speed-agility, balance and cardiorespiratory fitness) were assessed. Analysis of covariance adjusted for age, sex and height/body mass index (BMI) was used. RESULTS: Preschool children from Sweden had lower prevalence of overweight/obesity than their peers from Spain (World Obesity Federation, mean difference, MD = -9%, P = 0.010; World Health Organization, MD = -11%, P = 0.011). Concerning fitness, preschoolers from Spain were more fit in terms of upper-muscular strength (MD = +0.4 kg, P = 0.010), speed-agility (MD = -1.9 s, P = 0.001), balance (MD = +4.0 s, P = 0.001) and cardiorespiratory fitness (MD = boys = +6.6 laps, girls = +2.3 laps; P < 0.001 for all), yet they had worse lower-muscular strength (MD = -7.1, P ≤ 0.001) than those from Sweden. Differences in upper-muscular strength were largely explained by differences in BMI, and differences in cardiorespiratory fitness should be interpreted cautiously due to some methodological deviations. CONCLUSIONS: These findings suggest that a higher prevalence of overweight/obesity in Spain compared with Sweden is present already at early childhood, while differences in physical fitness components showed mixed findings.

Taccalonolide binding to tubulin imparts microtubule stability and potent in vivo activity.

The taccalonolides are highly acetylated steroids that stabilize cellular microtubules and overcome multiple mechanisms of taxane resistance. Recently, two potent taccalonolides, AF and AJ, were identified that bind to tubulin directly and enhance microtubule polymerization. Extensive studies were conducted to characterize these new taccalonolides. AF and AJ caused aberrant mitotic spindles and bundling of interphase microtubules that differed from the effects of either paclitaxel or laulimalide. AJ also distinctly affected microtubule polymerization in that it enhanced the rate and extent of polymerization in the absence of any noticeable effect on microtubule nucleation. In addition, the resulting microtubules were found to be profoundly cold stable. These data, along with studies showing synergistic antiproliferative effects between AJ and either paclitaxel or laulimalide, suggest a distinct binding site. Direct binding studies demonstrated that AJ could not be displaced from microtubules by paclitaxel, laulimalide, or denaturing conditions, suggesting irreversible binding of AJ to microtubules. Mass spectrometry confirmed a covalent interaction of AJ with a peptide of ß-tubulin containing the cyclostreptin-binding sites. Importantly, AJ imparts strong inter-protofilament stability in a manner different from other microtubule stabilizers that covalently bind to tubulin, consistent with the distinct effects of the taccalonolides as compared with other stabilizers. AF was found to be a potent and effective antitumor agent that caused tumor regression in the MDA-MB-231 breast cancer xenograft model. The antitumor efficacy of some taccalonolides, which stabilize microtubules in a manner different from other microtubule stabilizers, provides the impetus to explore the therapeutic potential of this site.

ELR510444, a novel microtubule disruptor with multiple mechanisms of action.

Although several microtubule-targeting drugs are in clinical use, there remains a need to identify novel agents that can overcome the limitations of current therapies, including acquired and innate drug resistance and undesired side effects. In this study, we show that ELR510444 has potent microtubule-disrupting activity, causing a loss of cellular microtubules and the formation of aberrant mitotic spindles and leading to mitotic arrest and apoptosis of cancer cells. ELR510444 potently inhibited cell proliferation with an IC(50) value of 30.9 nM in MDA-MB-231 cells, inhibited the rate and extent of purified tubulin assembly, and displaced colchicine from tubulin, indicating that the drug directly interacts with tubulin at the colchicine-binding site. ELR510444 is not a substrate for the P-glycoprotein drug transporter and retains activity in ßIII-tubulin-overexpressing cell lines, suggesting that it circumvents both clinically relevant mechanisms of drug resistance to this class of agents. Our data show a close correlation between the concentration of ELR510444 required for inhibition of cellular proliferation and that required to cause significant loss of cellular microtubule density, consistent with its activity as a microtubule depolymerizer. ELR510444 also shows potent antitumor activity in the MDA-MB-231 xenograft model with at least a 2-fold therapeutic window. Studies in tumor endothelial cells show that a low concentration of ELR510444 (30 nM) rapidly alters endothelial cell shape, similar to the effect of the vascular disrupting agent combretastatin A4. These results suggest that ELR510444 is a novel microtubule-disrupting agent with potential antivascular effects and in vivo antitumor efficacy.