pinecone/core-2020-05-10-deduplication huggingface dataset:
Dynamic transport in a quantum wire driven by spin-orbit interaction

We consider a gated one-dimensional (1D) quantum wire disturbed in a
contactless manner by an alternating electric field produced by a tip of a
scanning probe microscope. In this schematic 1D electrons are driven not by a
pulling electric field but rather by a non-stationary spin-orbit interaction
(SOI) created by the tip. We show that a charge current appears in the wire in
the presence of the Rashba SOI produced by the gate net charge and image
charges of 1D electrons induced on the gate (iSOI). The iSOI contributes to the
charge susceptibility by breaking the spin-charge separation between the
charge- and spin collective excitations, generated by the probe. The velocity
of the excitations is strongly renormalized by SOI, which opens a way to
fine-tune the charge and spin response of 1D electrons by changing the gate
potential. One of the modes softens upon increasing the gate potential to
enhance the current response as well as the power dissipated in the system.Comment: 4 pages, 2 figures; ref adde
Bi-stability of magnetic skyrmions in ultrathin multilayer nanodots
  induced by magnetostatic interaction

We report the results of simulations of magnetic skyrmion stability in
ultrathin magnetic multilayer nanodots with interfacial Dzyaloshinskii-Moriya
exchange interaction (DMI). We found that in presence of the lateral
confinement the magnetostatic energy significantly influences the skyrmion
stability and leads to stabilization of large radius skyrmion even at low
values of the DMI strength, in addition to small radius skyrmion stabilized by
DMI. In particular, stabilization of the skyrmion state with two different
radii (bi-stability) is found in dipolarly-coupled (Pt/Co/Ir)$_{n}$ circular
nanodots with the number of repeats of the unit cell $n$ = 3 and 5. The
bi-stability range is located at the DMI strength of 0.9-1.1 mJ/m$^2$ or at the
total Co-layer thickness of 2.2-2.6 nm
Low-temperature saw damage gettering to improve minority carrier lifetime in multicrystalline silicon

The minority carrier lifetime in multicrystalline silicon − a material used in the majority of today's manufactured solar cells − is limited by defects within the material, including metallic impurities which are relatively mobile at low temperatures (≤700 °C). Addition of an optimised thermal process which can facilitate impurity diffusion to the saw damage at the wafer surfaces can result in permanent removal of the impurities when the saw damage is etched away. We demonstrate that this saw damage gettering is effective at 500 to 700 °C and, when combined with subsequent low-temperature processing, lifetimes are improved by a factor of more than four relative to the as-grown state. The simple method has the potential to be a low thermal budget process for the improvement of low-lifetime “red zone” wafers
Dynamics of one-dimensional electrons with broken spin-charge separation

Spin-charge separation is known to be broken in many physically interesting
one-dimensional (1D) and quasi-1D systems with spin-orbit interaction because
of which spin and charge degrees of freedom are mixed in collective
excitations. Mixed spin-charge modes carry an electric charge and therefore can
be investigated by electrical means. We explore this possibility by studying
the dynamic conductance of a 1D electron system with image-potential-induced
spin-orbit interaction. The real part of the admittance reveals an oscillatory
behavior versus frequency that reflects the collective excitation resonances
for both modes at their respective transit frequencies. By analyzing the
frequency dependence of the conductance the mode velocities can be found and
their spin-charge structure can be determined quantitatively.Comment: 4 pages, 2 figures. updated to the published versio
A comparison of bootstrap approaches for estimating uncertainty of parameters in linear mixed-effects models.

International audienceA version of the nonparametric bootstrap, which resamples the entire subjects from original data, called the case bootstrap, has been increasingly used for estimating uncertainty of parameters in mixed-effects models. It is usually applied to obtain more robust estimates of the parameters and more realistic confidence intervals (CIs). Alternative bootstrap methods, such as residual bootstrap and parametric bootstrap that resample both random effects and residuals, have been proposed to better take into account the hierarchical structure of multi-level and longitudinal data. However, few studies have been performed to compare these different approaches. In this study, we used simulation to evaluate bootstrap methods proposed for linear mixed-effect models. We also compared the results obtained by maximum likelihood (ML) and restricted maximum likelihood (REML). Our simulation studies evidenced the good performance of the case bootstrap as well as the bootstraps of both random effects and residuals. On the other hand, the bootstrap methods that resample only the residuals and the bootstraps combining case and residuals performed poorly. REML and ML provided similar bootstrap estimates of uncertainty, but there was slightly more bias and poorer coverage rate for variance parameters with ML in the sparse design. We applied the proposed methods to a real dataset from a study investigating the natural evolution of Parkinson's disease and were able to confirm that the methods provide plausible estimates of uncertainty. Given that most real-life datasets tend to exhibit heterogeneity in sampling schedules, the residual bootstraps would be expected to perform better than the case bootstrap
A Bayesian dose-finding design for drug combination clinical trials based on the logistic model

International audienceIn early phase dose-finding cancer studies, the objective is to determine the maximum tolerated dose, defined as the highest dose with an acceptable dose-limiting toxicity rate. Finding this dose for drug-combination trials is complicated because of drug–drug interactions, and many trial designs have been proposed to address this issue. These designs rely on complicated statistical models that typically are not familiar to clinicians, and are rarely used in practice. The aim of this paper is to propose a Bayesian dose-finding design for drug combination trials based on standard logistic regression. Under the proposed design, we continuously update the posterior estimates of the model parameters to make the decisions of dose assignment and early stopping. Simulation studies show that the proposed design is competitive and outperforms some existing designs. We also extend our design to handle delayed toxicities. Copyright © 2014 John Wiley & Sons, Ltd
Impact of selection bias on the evaluation of clusters of chemical compounds in the drug discovery process

Expert opinion plays an important role when selecting promising clusters of chemical compounds in the drug discovery process. Indeed, experts can qualitatively assess the potential of each cluster, and with appropriate statistical methods, these qualitative assessments can be quantified into a success probability for each of them. However, one crucial element often overlooked is the procedure by which the clusters are assigned to/selected by the experts for evaluation. In the present work, the impact such a procedure may have on the statistical analysis and the entire evaluation process is studied. It has been shown that some implementations of the selection procedure may seriously compromise the validity of the evaluation even when the rating and selection processes are independent. Consequently, the fully random allocation of the clusters to the experts is strongly advocated. Copyright © 2014 John Wiley & Sons, Ltd.status: publishe
Structured benefit-risk assessment: a review of key publications and initiatives on frameworks and methodologies.

Introduction The conduct of structured benefit-risk assessment (BRA) of pharmaceutical products is a key area of interest for regulatory agencies and the pharmaceutical industry. However, the acceptance of a standardized approach and implementation are slow. Statisticians play major roles in these organizations, and have a great opportunity to be involved and drive the shaping of future BRA. Method We performed a literature search of recent reviews and initiatives assessing BRA methodologies, and grouped them to assist those new to BRA in learning, understanding, and choosing methodologies. We summarized the key points and discussed the impact of this emerging field on various stakeholders, particularly statisticians in the pharmaceutical industry. Results We provide introductory, essential, special interest, and further information and initiatives materials that direct readers to the most relevant materials, which were published between 2000 and 2013.  Based on recommendations in these materials we supply a toolkit of advocated BRA methodologies. Discussion Despite initiatives promoting these methodologies, there are still barriers, one of which being the lack of a consensus on the most appropriate methodologies among stakeholders. However, this opens up opportunities, for statisticians in the pharmaceutical industry especially, to champion appropriate BRA methodology use throughout the pharmaceutical product lifecycle. Conclusions This article may serve as a starting point for discussions and to reach a mutual consensus for methodology selection in a particular situation. Regulators and pharmaceutical industry should continue to collaborate to develop and take forward BRA methodologies, and by clear communication develop a mutual understanding of the key issues. Copyright © 2015 John Wiley & Sons, Ltd
Carryover negligibility and relevance in bioequivalence studies

The carryover effect is a recurring issue in the pharmaceutical field. It may strongly influence the final outcome of an average bioequivalence study. Testing a null hypothesis of zero carryover is useless: not rejecting it does not guarantee the non-existence of carryover, and rejecting it is not informative of the true degree of carryover and its influence on the validity of the final outcome of the bioequivalence study. We propose a more consistent approach: even if some carryover is present, is it enough to seriously distort the study conclusions or is it negligible? This is the central aim of this paper, which focuses on average bioequivalence studies based on 2×2 crossover designs and on the main problem associated with carryover: type I error inflation. We propose an equivalence testing approach to these questions and suggest reasonable negligibility or relevance limits for carryover. Finally, we illustrate this approach on some real datasets
Model free audit methodology for bias evaluation of tumour progression in oncology

Many oncology studies incorporate a blinded independent central review (BICR) to make an assessment of the integrity of the primary endpoint, progression free survival. Recently, it has been suggested that, in order to assess the potential for bias amongst investigators, a BICR amongst only a sample of patients could be performed; if evidence of bias is detected, according to a predefined threshold, the BICR is then assessed in all patients, otherwise, it is concluded that the sample was sufficient to rule out meaningful levels of bias. In this paper, we present an approach that adapts a method originally created for defining futility bounds in group sequential designs. The hazard ratio ratio, the ratio of the hazard ratio (HR) for the treatment effect estimated from the BICR to the corresponding HR for the investigator assessments, is used as the metric to define bias. The approach is simple to implement and ensures a high probability that a substantial true bias will be detected. In the absence of bias, there is a high probability of accepting the accuracy of local evaluations based on the sample, in which case an expensive BICR of all patients is avoided. The properties of the approach are demonstrated by retrospective application to a completed Phase III trial in colorectal cancer. The same approach could easily be adapted for other disease settings, and for test statistics other than the hazard ratio
Do single-arm trials have a role in drug development plans incorporating randomised trials?

Often, single-arm trials are used in phase II to gather the first evidence of an oncological drug’s efficacy; with drug activity determined through tumour response using the RECIST criterion. Provided the null hypothesis of ‘insufficient drug activity’ is rejected, the next step could be a randomised two-arm trial. However, single-arm trials may provide a biased treatment effect due to patient selection, and thus this development plan may not be an efficient use of resources. Therefore, we compare the performance of development plans consisting of single-arm trials followed by randomised two-arm trials, to stand-alone single-stage or group sequential randomised two-arm trials. Through this we are able to investigate the utility of single-arm trials, and determine the most efficient drug development plans, setting our work in the context of a published single-arm non-small-cell lung cancer trial. Reference priors, reflecting the opinions of ‘sceptical’ and ‘enthusiastic’ investigators, are used to quantify and guide the suitability of single-arm trials in this setting. We observe that the explored development plans incorporating single-arm trials are often non-optimal. Moreover, even the most pessimistic reference priors have a considerable probability in favour of alternative plans. Analysis suggests expected sample size savings of up to 25% could have been made, and the issues associated with single-arm trials avoided, for the non-small-cell lung cancer treatment through direct progression to a group sequential randomised two-arm trial. Careful consideration should thus be given to the use of single-arm trials in oncological drug development when a randomised trial will follow.Michael J. Grayling is supported by the Wellcome Trust [grant number 099770/Z/12/Z]. Adrian P. Mander is supported by the Medical Research Council [grant number G0800860].This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/pst.172
Α Markov model for longitudinal studies with incomplete dichotomous outcomes.

Missing outcome data constitute a serious threat to the validity and precision of inferences from randomized controlled trials. In this paper, we propose the use of a multistate Markov model for the analysis of incomplete individual patient data for a dichotomous outcome reported over a period of time. The model accounts for patients dropping out of the study and also for patients relapsing. The time of each observation is accounted for, and the model allows the estimation of time-dependent relative treatment effects. We apply our methods to data from a study comparing the effectiveness of 2 pharmacological treatments for schizophrenia. The model jointly estimates the relative efficacy and the dropout rate and also allows for a wide range of clinically interesting inferences to be made. Assumptions about the missingness mechanism and the unobserved outcomes of patients dropping out can be incorporated into the analysis. The presented method constitutes a viable candidate for analyzing longitudinal, incomplete binary data
Statistical issues in first-in-human studies on BIA 10-2474: neglected comparison of protocol against practice

Funding information: European Union's FP7 programme, Grant/Award Number: 602552By setting the regulatory-approved protocol for a suite of first-in-human studies on BIA 10-2474 against the subsequent French investigations, we highlight six key design and statistical issues which reinforce recommendations by a Royal Statistical Society Working Party which were made in the aftermath of cytokine release storm in six healthy volunteers in the UK in 2006. The 6 issues are dose determination, availability of pharmacokinetic results, dosing interval, stopping rules, appraisal by safety committee, and clear algorithm required if combining approvals for single and multiple ascending dose studies.PostprintPeer reviewe
Inhibitory effect against polymerase and ribonuclease activities of HIV-reverse transcriptase of the aqueous leaf extract of Terminalia triflora

Dichloromethane, methanol and aqueous extracts from the leaves of Terminalia triflora were investigated for their inhibitory effect on polymerase and ribonuclease activities of HIV reverse transcriptase.The most potent activity was found in the aqueous extract, which inhibited both polymerase and ribonuclease activities of the enzyme with an IC50 of 1.6 micro g/mL and 1.8 micro g/mL respectively. The antiinfective activity of the extract was demonstrated in HLT4LacZ-IIIB cell culture with an IC50 of 1.0 micro g/mL. The extract was submitted to a purification process by extractive and chromatographic methods. The activity remained in the hydrophillic fraction. Tannins present in this active purified fraction, as determined by TLC and HPLC methods, could account for the anti HIV-RT activity found in the aqueous extract
Effect of a diterpenoid from Salvia cinnabarina on arterial blood pressure in rats.

The effect of a diterpenoid isolated from Salvia cinnabarina, 3,4-seicosopimar-4(18),7,15-triene-3-oic acid\ud
(SCB), on arterial blood pressure was evaluated in anaesthetized rats.\ud
Male Wistar rats, anaesthetized with urethane (sol. 10% p/v; 10 mL/kg), underwent surgery for continuous\ud
monitoring of arterial blood pressure. After preliminary experiments to evaluate the dose response (3, 10 and\ud
30 mg/kg i.v.) of SCB, a dose of 3 mg/kg was chosen for all successive experiments. On different groups of rats\ud
treated with the ganglion-blocking agent chlorisondamine (2.5 mg/kg i.p.) the effect of SCB (3 mg/kg i.v.) was\ud
evaluated before and following an infusion of the nitric oxide synthase inhibitor L-NAME (0.3 mg/kg/min i.v.).\ud
Intravenous administration of SCB at doses of 3, 10 and 30 mg/kg led to a fall in mean arterial blood pressure\ud
(MABP) of 14.75 ± 1.44 mmHg, 36.60 ± 31.40 mmHg and 31.40 ± 6.28 mmHg, respectively (n = 4–5), that was\ud
not modified by treatment of the rat with chlorisondamine nor with L-NAME. The results demonstrate a\ud
hypotensive effect of SCB – due to a peripheral mechanism but independent of endothelial nitric oxide\ud
release
Effect of North American Ginseng on 137Cs-induced Micronuclei in Human Lymphocytes

To explore the radioprotective effect of a standardized North American ginseng extract (NAGE) on human peripheral blood lymphocytes (PBL), a micronuclei (MN) assay was conducted in PBL obtained from 12 volunteers. NAGE (50â  1000 Âµg/mL) and WR-1065 (1 mm and 3 mm) were applied to PBL cultures at 0 h and 90 min post-irradiation. It was found that (1) the baseline MN yield of PBL ranged from 14.4 Â± 1.5 to 15.9 Â± 1.5 per 1000 binucleated cells (p > 0.05); after irradiation (1 Gy and 2 Gy), the MN yield increased sharply; (2) MN yields declined with increasing concentrations of NAGE and WR-1065. Even at 90 min post-irradiation of 1 Gy, the maximum level of MN reduction rate caused by NAGE and WR-1065 was 53.8% and 59.2%, respectively; after 2 Gy irradiation, it was 37.3% and 42%, respectively; (3) the MN distribution in PBL followed a non-Poisson distribution in all cases; and (4) both NAGE and WR-1065 showed no significant effect on the proliferation index of lymphocytes. The results indicate that NAGE is a relatively non-toxic natural product, which can be administered as a dietary supplement and has the potential to be a radiation countermeasure. Originally published Phytotherapy Research Vol. 22, No. 12 2008
An antibacterial and antifungal phenylpropanoid from Carum montanum (Coss. et Dur.) Benth. et Hook.

International audienceThe volatile constituents of the aerial parts of Carum montanum (Coss. et Dur.) Benth. et Hook. were analysed by GC-FID and GC-MS, and the main component was isolated and identified as nothoapiole. The antibacterial and antifungal activities of this compound and of the total oil were investigated against Gram negative (P. aeruginosa, E. coli), Gram positive (E. faecalis, S. aureus, S. epidermitis, S. saprophyticus, S. simulans, S. lugdunensis) bacteria and on one strain of fungus (C. tropicalis)
Effect of Aloe barbadensis Miller juice on oxidative stress biomarkers in aerobic cells using Artemia franciscana as a model

This study reports on the induction of oxidative stress in aerobic cell systems by Aloe barbadensis Miller (Aloe vera) juice using the salt water crustacean Artemia franciscana as a model. A consistent pattern was observed where Artemia franciscana nauplii responded to Aloe vera juice exposure with a decrease in the overall activity of redox related enzymes. Exposure of Artemia franciscana to sub-lethal levels of Aloe vera juice resulted in a decreased activity of thioredoxin reductase, glutathione reductase and glutathione peroxidase by 34% (66 % enzymatic activity), 79% (21 % enzymatic activity) and 90% (10 % enzymatic activity) respectively. Similarly apparent was the trend whereby the co-exposure of the nauplii to vitamin E counteracted this effect. For each of the biomarker enzymes tested, vitamin E co-exposure resulted in enzyme activities closer to the control value (78%, 56% and 32% of control enzymatic activities for thioredoxin reductase, glutathione reductase and glutathione peroxidase activity respectively). These results indicate that exposure to sub-lethal doses of Aloe vera juice induces alterations in the cellular redox status of Artemia franciscana and that vitamin E addition helps the Artemia franciscana nauplii to overcome/block the juice induced oxidative stress.Griffith Sciences, School of Natural SciencesFull Tex
Ursolic acid and luteolin-7-glucoside improves rat plasma lipid profile and increases liver glycogen content through glycogen synthase kinase-3

In the present study, two phytochemicals - ursolic acid (UA) and luteolin-7-glucoside (L7G) - were assessed in vivo in healthy rats regarding effects on plasma glucose and lipid profile (total cholesterol, HDL and LDL), as well as liver glycogen content, in view of their importance in the aetiology of diabetes and associated complications. Both UA and L7G significantly decreased plasma glucose concentration. UA also significantly increased liver glycogen levels accompanied by phosphorylation of glycogen synthase kinase-3 (GSK3). The increase in glycogen deposition induced by UA (mediated by GSK3) could have contributed to the lower plasma glucose levels observed. Both compounds significantly lowered total plasma cholesterol and low-density lipoprotein levels, and, in addition, UA increased plasma high-density lipoprotein levels. Our results show that UA particularly may be useful in preventable strategies for people at risk of developing diabetes and associated cardiovascular complications by improving plasma glucose levels and lipid profile, as well as by promoting liver glycogen deposition.MFA and CMS were supported by the Foundation for Science and Technology, Portugal, through the grants SFRH/BD/12527/2003 and SFRH/BD/42566/2007, respectively. This work was supported by the Foundation for Science and Technology, Portugal, research grant POCI/AGR/62040/2004