2,058 research outputs found
Comparison of techniques for handling missing covariate data within prognostic modelling studies: a simulation study
Background: There is no consensus on the most appropriate approach to handle missing covariate data within prognostic modelling studies. Therefore a simulation study was performed to assess the effects of different missing data techniques on the performance of a prognostic model.
Methods: Datasets were generated to resemble the skewed distributions seen in a motivating breast cancer example. Multivariate missing data were imposed on four covariates using four different mechanisms; missing completely at random (MCAR), missing at random (MAR), missing not at random (MNAR) and a combination of all three mechanisms. Five amounts of incomplete cases from 5% to 75% were considered. Complete case analysis (CC), single imputation (SI) and five multiple imputation (MI) techniques available within the R statistical software were investigated: a) data augmentation (DA) approach assuming a multivariate normal distribution, b) DA assuming a general location model, c) regression switching imputation, d) regression switching with predictive mean matching (MICE-PMM) and e) flexible additive imputation models. A Cox proportional hazards model was fitted and appropriate estimates for the regression coefficients and model performance measures were obtained.
Results: Performing a CC analysis produced unbiased regression estimates, but inflated standard errors, which affected the significance of the covariates in the model with 25% or more missingness. Using SI, underestimated the variability; resulting in poor coverage even with 10% missingness. Of the MI approaches, applying MICE-PMM produced, in general, the least biased estimates and better coverage for the incomplete covariates and better model performance for all mechanisms. However, this MI approach still produced biased regression coefficient estimates for the incomplete skewed continuous covariates when 50% or more cases had missing data imposed with a MCAR, MAR or combined mechanism. When the missingness depended on the incomplete covariates, i.e. MNAR, estimates were biased with more than 10% incomplete cases for all MI approaches.
Conclusion: The results from this simulation study suggest that performing MICE-PMM may be the preferred MI approach provided that less than 50% of the cases have missing data and the missing data are not MNAR
Simplified three-dimensional finite element hot-spotting modelling of a pin-mounted vented brake disc: an investigation of hot-spotting determinants
YesHot spotting is a thermal localisation phenomenon in which multiple hot regions form on a brake disc surface during high energy and/or high speed braking events. As an undesired problem, hot spots can result in high order brake judder, audible drone and thermal cracking. This paper presents a finite element model for hot spot modelling which introduces the classical axisymmetric assumptions to the brake pad in 3D by scaling the material properties combined with a subroutine to simulate the heat generation instead of modelling the rotation of the brake pad. The results from the initial feasibility models showed significant improvement in computing efficiency with acceptable accuracy when compared to a traditional FE model without such simplifications. This method was then applied to the 3D simulation of hot spotting on a realistic ventilated brake disc/pad pair and the results showed good correlation with experiments. In order to improve the understanding of the hot spotting mechanism, parametric studies were performed including the effects of solid and ventilated disc geometry, rotational speed and energy, pins, disc run-out, and brake pad length. Based on the analysis of the results, it was identified that the vents and pins affected the hot spot distribution. Speed was shown to be more important on the hot spot generation time and distribution than either the pressure or total energy input. Brake disc run-out was shown to affect the magnitude of both hot spot temperature and height due to the non-linear relationship between local deformation, contact pressure and heat generation. Finally, increasing the brake pad length generated fewer hot spots but the temperature of each hot spot increased
Experimental GHZ Entanglement beyond Qubits
The Greenberger-Horne-Zeilinger (GHZ) argument provides an all-or-nothing
contradiction between quantum mechanics and local-realistic theories. In its
original formulation, GHZ investigated three and four particles entangled in
two dimensions only. Very recently, higher dimensional contradictions
especially in three dimensions and three particles have been discovered but it
has remained unclear how to produce such states. In this article we
experimentally show how to generate a three-dimensional GHZ state from
two-photon orbital-angular-momentum entanglement. The first suggestion for a
setup which generates three-dimensional GHZ entanglement from these entangled
pairs came from using the computer algorithm Melvin. The procedure employs
novel concepts significantly beyond the qubit case. Our experiment opens up the
possibility of a truly high-dimensional test of the GHZ-contradiction which,
interestingly, employs non-Hermitian operators.Comment: 6+6 pages, 8 figure
Strain-induced partially flat band, helical snake states, and interface superconductivity in topological crystalline insulators
Topological crystalline insulators in IV-VI compounds host novel topological
surface states consisting of multi-valley massless Dirac fermions at low
energy. Here we show that strain generically acts as an effective gauge field
on these Dirac fermions and creates pseudo-Landau orbitals without breaking
time-reversal symmetry. We predict the realization of this phenomenon in IV-VI
semiconductor heterostructures, due to a naturally occurring misfit dislocation
array at the interface that produces a periodically varying strain field.
Remarkably, the zero-energy Landau orbitals form a flat band in the vicinity of
the Dirac point, and coexist with a network of snake states at higher energy.
We propose that the high density of states of this flat band gives rise to
interface superconductivity observed in IV-VI semiconductor multilayers at
unusually high temperatures, with non-BCS behavior. Our work demonstrates a new
route to altering macroscopic electronic properties to achieve a partially flat
band, and paves the way for realizing novel correlated states of matter.Comment: Accepted by Nature Physic
The Wnt inhibitory factor 1 restoration in prostate cancer cells was associated with reduced tumor growth, decreased capacity of cell migration and invasion and a reversal of epithelial to mesenchymal transition
<p>Abstract</p> <p>Background</p> <p>Aberrations in the Wnt pathway have been reported to be involved in the metastasis of prostate cancer (PCa) to bone. We investigated the effect and underlying mechanism of a naturally-occurring Wnt inhibitor, WIF1, on the growth and cellular invasiveness of a bone metastatic PCa cell line, PC3.</p> <p>Results</p> <p>The WIF1 gene promoter was hypermethylated and its expression down-regulated in the majority (7 of 8) of PCa cell lines. Restoration of WIF1 expression in PC-3 cells resulted in a decreased cell motility and invasiveness via up-regulation of epithelial markers (E-cadherin, Keratin-8 and-18), down-regulation of mesenchymal markers (N-cadherin, Fibronectin and Vimentin) and decreased activity of MMP-2 and -9. PC3 cells transfected with WIF1 consistently demonstrated reduced expression of Epithelial-to-Mesenchymal Transition (EMT) transcription factors, Slug and Twist, and a change in morphology from mesenchymal to epithelial. Moreover, WIF1 expression significantly reduced tumor growth by approximately 63% in a xenograft mouse model. This was accompanied by an increased expression of E-cadherin and Keratin-18 and a decreased expression of vimentin in tumor tissues.</p> <p>Conclusion</p> <p>These data suggest that WIF1 regulates tumor invasion through EMT process and thus, may play an important role in controlling metastatic disease in PCa patients. Blocking Wnt signaling in PCa by WIF1 may represent a novel strategy in the future to reduce metastatic disease burden in PCa patients.</p
Fabrication of Densely Packed AlN Nanowires by a Chemical Conversion of Al2O3Nanowires Based on Porous Anodic Alumina Film
Porous alumina film on aluminum with gel-like pore wall was prepared by a two-step anodization of aluminum, and the corresponding gel-like porous film was etched in diluted NaOH solution to produce alumina nanowires in the form of densely packed alignment. The resultant alumina nanowires were reacted with NH3and evaporated aluminum at an elevated temperature to be converted into densely packed aluminum nitride (AlN) nanowires. The AlN nanowires have a diameter of 15–20 nm larger than that of the alumina nanowires due to the supplement of the additional evaporated aluminum. The results suggest that it might be possible to prepare other aluminum compound nanowires through similar process
Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay
The decay channel
is studied using a sample of events collected
by the BESIII experiment at BEPCII. A strong enhancement at threshold is
observed in the invariant mass spectrum. The enhancement can be fit
with an -wave Breit-Wigner resonance function with a resulting peak mass of
and a
narrow width that is at the 90% confidence level.
These results are consistent with published BESII results. These mass and width
values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics
Antiferromagnetic spintronics
Antiferromagnetic materials are magnetic inside, however, the direction of
their ordered microscopic moments alternates between individual atomic sites.
The resulting zero net magnetic moment makes magnetism in antiferromagnets
invisible on the outside. It also implies that if information was stored in
antiferromagnetic moments it would be insensitive to disturbing external
magnetic fields, and the antiferromagnetic element would not affect
magnetically its neighbors no matter how densely the elements were arranged in
a device. The intrinsic high frequencies of antiferromagnetic dynamics
represent another property that makes antiferromagnets distinct from
ferromagnets. The outstanding question is how to efficiently manipulate and
detect the magnetic state of an antiferromagnet. In this article we give an
overview of recent works addressing this question. We also review studies
looking at merits of antiferromagnetic spintronics from a more general
perspective of spin-ransport, magnetization dynamics, and materials research,
and give a brief outlook of future research and applications of
antiferromagnetic spintronics.Comment: 13 pages, 7 figure
Altering crystal growth and annealing in ice-templated scaffolds.
The potential applications of ice-templating porous materials are constantly expanding, especially as scaffolds for tissue engineering. Ice-templating, a process utilizing ice nucleation and growth within an aqueous solution, consists of a cooling stage (before ice nucleation) and a freezing stage (during ice formation). While heat release during cooling can change scaffold isotropy, the freezing stage, where ice crystals grow and anneal, determines the final size of scaffold features. To investigate the path of heat flow within collagen slurries during solidification, a series of ice-templating molds were designed with varying the contact area with the heat sink, in the form of the freeze drier shelf. Contact with the heat sink was found to be critical in determining the efficiency of the release of latent heat within the perspex molds. Isotropic collagen scaffolds were produced with pores which ranged from 90 μm up to 180 μm as the contact area decreased. In addition, low-temperature ice annealing was observed within the structures. After 20 h at -30 °C, conditions which mimic storage prior to lyophilization, scaffold architecture was observed to coarsen significantly. In future, ice-templating molds should consider not only heat conduction during the cooling phase of solidification, but the effects of heat flow during ice growth and annealing.The authors gratefully acknowledge the financial support of the Gates Cambridge Trust, the Newton Trust, and ERC Advanced Grant 320598 3D-E. A.H. held a Daphne Jackson Fellowship funded by the University of Cambridge.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10853-015-9343-
The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum
The endoplasmic reticulum (ER) is a large, multifunctional and essential organelle. Despite intense research, the function of more than a third of ER proteins remains unknown even in the well-studied model organism Saccharomyces cerevisiae. One such protein is Spf1, which is a highly conserved, ER localized, putative P-type ATPase. Deletion of SPF1 causes a wide variety of phenotypes including severe ER stress suggesting that this protein is essential for the normal function of the ER. The closest homologue of Spf1 is the vacuolar P-type ATPase Ypk9 that influences Mn2+ homeostasis. However in vitro reconstitution assays with Spf1 have not yielded insight into its transport specificity. Here we took an in vivo approach to detect the direct and indirect effects of deleting SPF1. We found a specific reduction in the luminal concentration of Mn2+ in ∆spf1 cells and an increase following it’s overexpression. In agreement with the observed loss of luminal Mn2+ we could observe concurrent reduction in many Mn2+-related process in the ER lumen. Conversely, cytosolic Mn2+-dependent processes were increased. Together, these data support a role for Spf1p in Mn2+ transport in the cell. We also demonstrate that the human sequence homologue, ATP13A1, is a functionally conserved orthologue. Since ATP13A1 is highly expressed in developing neuronal tissues and in the brain, this should help in the study of Mn2+-dependent neurological disorders
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