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Magnetic skyrmions are topologically protected spin textures with promising prospects for applications in data storage. They can form a lattice state due to competing magnetic interactions and are commonly found in a small region of the temperature—magnetic field phase diagram. Recent work has demonstrated that these magnetic quasi-particles fluctuate at the μeV energy scale. Here, we use a coherent x-ray correlation method at an x-ray free-electron laser to investigate these fluctuations in a magnetic phase coexistence region near a first-order transition boundary where fluctuations are not expected to play a major role. Surprisingly, we find that the relaxation of the intermediate scattering function at this transition differs significantly compared to that deep in the skyrmion lattice phase. The observation of a compressed exponential behavior suggests solid-like dynamics, often associated with jamming. We assign this behavior to disorder and the phase coexistence observed in a narrow field-window near the transition, which can cause fluctuations that lead to glassy behavior. [ABSTRACT FROM AUTHOR]

The studies have searched for a signature of nonlocal magnetization dynamics or magnetization dynamics driven by pure spin currents, in magnetically soft polycrystalline [Ni.sub.81][Fe.sub.19]/Cu/[Co.sub.93][Zr.sub.7] trilayers by using ferromagnetic resonance. An interface-related increase of damping is seen for each ferromagnetic layer when incorporated in a trilayer and the size effects are identified in Gilbert damping.

The microwave properties of monodisperse, superparamagnetic [gamma]-[fe.sub.2][O.sub.3] nanoparticle array are examined by using broadband ferromagnetic resonance. Resonance linewidths are described by the natural thermal dispersion in properties of the system.

We have searched for a signature of nonlocal magnetization dynamics or magnetization dynamics driven by pure spin currents, in magnetically soft polycrystalline Ni81Fe19/Cu/Co93Zr7 trilayers using ferromagnetic resonance. An interface-related enhancement of damping is expected for each ferromagnetic layer when incorporated in a trilayer; the enhancement should be absent where layer resonances overlap. While size effects in Gilbert damping have been identified, we note that expectations specific to spin pumping are not confirmed. [ABSTRACT FROM AUTHOR]

We have investigated the microwave properties of monodisperse, superparamagnetic γ-Fe2O3 nanoparticle arrays using broadband ferromagnetic resonance. We identify a novel field for resonance relationship in the films. Compared with ferromagnetic films of equal magnetization, resonance frequencies are suppressed for in-plane magnetization and enhanced for out-of-plane magnetization, over the range of 0–8 Ghz. The behavior identified is that of a superparamagnetic thin film, where thin-film dipolar fields act on a gradually saturating magnetization described by the Langevin function. Resonance linewidths can be described by the natural thermal dispersion in properties of the system. [ABSTRACT FROM AUTHOR]

X-ray beam stability is crucial for acquiring high-quality data at synchrotron beamline facilities. When the X-ray beam and defining apertures are of similar dimensions, small misalignments driven by position instabilities give rise to large intensity fluctuations. This problem is solved using extremum seeking feedback control (ESFC) for in situ vertical beam position stabilization. In this setup, the intensity spatial gradient required for ESFC is determined by phase comparison of intensity oscillations downstream from the sample with pre-existing vertical beam oscillations. This approach compensates for vertical position drift from all sources with position recovery times <6 s and intensity stability through a 5 µm aperture measured at 1.5% FWHM over a period of 8 hours. [ABSTRACT FROM AUTHOR]

Background: Response-adaptive randomisation designs have been proposed to improve the efficiency of phase III randomised clinical trials and improve the outcomes of the clinical trial population. In the setting of failure time outcomes, Zhang and Rosenberger (2007) developed a response-adaptive randomisation approach that targets an optimal allocation, based on a fixed sample size.Objectives: The aim of this research is to propose a response-adaptive randomisation procedure for survival trials with an interim monitoring plan, based on the following optimal criterion: for fixed variance of the estimated log hazard ratio, what allocation minimizes the expected hazard of failure? We demonstrate the utility of the design by redesigning a clinical trial on multiple myeloma.Methods: To handle continuous monitoring of data, we propose a Bayesian response-adaptive randomisation procedure, where the log hazard ratio is the effect measure of interest. Combining the prior with the normal likelihood, the mean posterior estimate of the log hazard ratio allows derivation of the optimal target allocation. We perform a simulation study to assess and compare the performance of this proposed Bayesian hybrid adaptive design to those of fixed, sequential or adaptive - either frequentist or fully Bayesian - designs. Non informative normal priors of the log hazard ratio were used, as well as mixture of enthusiastic and skeptical priors. Stopping rules based on the posterior distribution of the log hazard ratio were computed. The method is then illustrated by redesigning a phase III randomised clinical trial of chemotherapy in patients with multiple myeloma, with mixture of normal priors elicited from experts.Results: As expected, there was a reduction in the proportion of observed deaths in the adaptive vs. non-adaptive designs; this reduction was maximized using a Bayes mixture prior, with no clear-cut improvement by using a fully Bayesian procedure. The use of stopping rules allows a slight decrease in the observed proportion of deaths under the alternate hypothesis compared with the adaptive designs with no stopping rules.Conclusions: Such Bayesian hybrid adaptive survival trials may be promising alternatives to traditional designs, reducing the duration of survival trials, as well as optimizing the ethical concerns for patients enrolled in the trial. [ABSTRACT FROM AUTHOR]

We use X-ray Excited Luminescence Microscopy to investigate the elemental and layer resolved magnetic reversal in an interlayer exchange coupled (IEC) epitaxial Fe/Cr wedge/Co heterostructure. The transition from strongly coupled parallel Co-Fe reversal for Cr thickness tCr<0.34 nm to weakly coupled layer independent reversal for tCr>1.5 nm is punctuated at 0.34

The aim of phase I combination dose-finding studies in oncology is to estimate one or several maximum tolerated doses (MTDs) from a set of available dose levels of two or more agents. Combining several agents can indeed increase the overall anti-tumor action but at the same time also increase the toxicity. It is, however, unreasonable to assume the same dose-toxicity relationship for the combination as for the simple addition of each single agent because of a potential antagonist or synergistic effect. Therefore, using single-agent dose-finding methods for combination therapies is not appropriate. In recent years, several authors have proposed novel dose-finding designs for combination studies, which use either algorithm-based or model-based methods. The aim of our work was to compare, via a simulation study, six dose-finding methods for combinations proposed in recent years. We chose eight scenarios that differ in terms of the number and location of the true MTD(s) in the combination space. We then compared the performance of each design in terms of correct combination selection, patient allocation, and mean number of observed toxicities during the trials. Our results showed that the model-based methods performed better than the algorithm-based ones. However, none of the compared model-based designs gave consistently better results than the others. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We give the first subexponential time deterministic polynomial identity testing algorithm for depth-4 multilinear circuits with a small top fan-in. More accurately, our algorithm works for depth-4 multilinear circuits with a plus gate at the top (also known as ΣΠΣΠ circuits) and has a running time of exp(poly(log(n), log(s), k)) where n is the number of variables, s is the size of the circuit, and k is the fan-in of the top gate. In particular, when the circuit is of polynomial (or quasi-polynomial) size, our algorithm runs in quasi-polynomial time. Prior to this work, sub-exponential time deterministic algorithms were known for depth-3 circuits with small top fan-in and for very restricted versions of depth-4 circuits. The main ingredient in our proof is a new structural theorem for multilinear ΣΠΣΠ(k) circuits. Roughly, this theorem shows that any nonzero multilinear ΣΠΣΠ(k) circuit contains an "embedded" nonzero multilinear ΣΠΣΠ(k) circuit. Using ideas from previous works on identity testing of sums of read-once formulas and of depth-3 multilinear circuits, we are able to exploit this structure and obtain an identity testing algorithm for multilinear ΣΠΣΠ(k) circuits. [ABSTRACT FROM AUTHOR]

The role of core promoter elements in regulating transcription initiation is largely unknown for genes subject to complex regulation. Major histocompatibility complex class I genes are ubiquitously expressed and governed by tissue-specific and hormonal signals. Transcription initiates at multiple sites within the core promoter, which contains elements homologous to the canonical elements CCAAT, TATAA, Sp1 binding site (Sp1BS), and Initiator (Inr). To determine their functions, expression of class I transgenes with individually mutated elements was assessed. Surprisingly, all mutant promoters supported transcription. However, each mutated core promoter element had a distinct effect on expression: CAAT box mutations modulated constitutive expression in nonlymphoid tissues, whereas TATAA-like element mutations dysregulated transcription in lymphoid tissues. Inr mutations aberrantly elevated expression. Sp1BS element mutations resulted in variegated transgene expression. RNA polymerase II binding and histone H3K4me3 patterns correlated with transgene expression; H3K9me3 marks partially correlated. Whereas the wild-type, TATAA-like, and CAAT mutant promoters were activated by gamma interferon, the Sp1 and Inr mutants were repressed, implicating these elements in regulation of hormonal responses. These results lead to the surprising conclusion that no single element is required for promoter activity. Rather, each plays a distinct role in promoter activity, chromatin structure, tissue-specific expression, and extracellular signaling. [ABSTRACT FROM AUTHOR]

We construct a small set of explicit linear transformations mapping ℝn to ℝt, where t = O(log(γ-1)ε-2), such that the L2 norm of any vector in ℝn is distorted by at most 1 ± ε in at least a fraction of 1-γ of the transformations in the set. Albeit the tradeoff between the size of the set and the success probability is suboptimal compared with probabilistic arguments, we nevertheless are able to apply our construction to a number of problems. In particular, we use it to construct an ε-sample (or pseudorandom generator) for linear threshold functions on 픔n-1 for ε = o(1). We also use it to construct an ε-sample for spherical digons in 픔n-1 for ε = o(1). This construction leads to an efficient oblivious derandomization of the Goemans-Williamson Max-Cut algorithm and similar approximation algorithms (i.e., we construct a small set of hyperplanes such that for any instance we can choose one of them to generate a good solution). Our technique for constructing an ε-sample for linear threshold functions on the sphere is considerably different than previous techniques that rely on k-wise independent sample spaces. [ABSTRACT FROM AUTHOR]

We present a compact sample holder equipped with electromagnets and high frequency transmission lines; the sample holder is intended for combined x-ray magnetic circular dichroism (XMCD) and ferromagnetic resonance measurements (FMR). Time-resolved measurements of resonant x-ray detected FMR during forced precession are enabled by use of a rf excitation that is phase-locked to the storage ring bunch clock. Several applications of the combined XMCD+FMR technique are presented, demonstrating the flexibility of the experimental design. [ABSTRACT FROM AUTHOR]

To determine the maximum-tolerated dose (MTD), dose-limiting toxicities and pharmacokinetic of semisynthetic homoharringtonine (ssHHT), given as a twice daily subcutaneous (s.c.) injections for 9 days, in patients with advanced acute leukaemia, 18 patients with advanced acute myeloid leukaemia were included in this sequential Bayesian phase I dose-finding trial. A starting dose of 0.5 mg m−2 day−1 was explored with subsequent dose escalations of 1, 3, 5 and 6 mg m−2 day−1. Myelosuppression was constant. The MTD was estimated as the dose level of 5 mg m−2 day−1 for 9 consecutive days by s.c. route. Dose-limiting toxicities were hyperglycaemia with hyperosmolar coma at 3 mg m−2, and (i) one anasarque and haematemesis, (ii) one life-threatening pulmonary aspergillosis, (iii) one skin rash and (iv) one scalp pain at dose level of 5 mg m−2 day−1. The mean half-life of ssHHT was 11.01±3.4 h, the volume of distribution at steady state was 2±1.4 l kg−1 and the plasma clearance was 11.6±10.4 l h−1. Eleven of the 12 patients with circulating leukaemic cells had blood blast clearance, two achieved complete remission and one with blast crisis of CMML returned in chronic phase. The recommended daily dose of ssHHT on the 9-day schedule is 5 mg m−2 day−1.British Journal of Cancer (2006) 95, 253–259. doi:10.1038/sj.bjc.6603265 www.bjcancer.com Published online 18 July 2006 [ABSTRACT FROM AUTHOR]

We review the rationale behind the statistical design of dose-finding studies as used in phase I and phase I/II clinical trials. We underline what the objectives of such dose-finding studies should be and why the widely used standard design fails to meet any of these objectives. The standard design is a "memoryless" design and we discuss how this impacts on practical behaviour. Designs introduced over the last two decades can be viewed as designs with memory and we discuss how these designs are superior to memoryless designs. By superior we mean that they require less patients overall, less patients to attain the maximum tolerated dose (MTD), and concentrate a higher percentage of patients at and near to the MTD. We reanalyse some recently published studies in order to provide support to our contention that markedly better results could have been achieved had a design with memory been used instead of a memoryless design. [ABSTRACT FROM AUTHOR]