351 research outputs found
Topological Defects in Nematic Droplets of Hard Spherocylinders
Using computer simulations we investigate the microscopic structure of the
singular director field within a nematic droplet. As a theoretical model for
nematic liquid crystals we take hard spherocylinders. To induce an overall
topological charge, the particles are either confined to a two-dimensional
circular cavity with homeotropic boundary or to the surface of a
three-dimensional sphere. Both systems exhibit half-integer topological point
defects. The isotropic defect core has a radius of the order of one particle
length and is surrounded by free-standing density oscillations. The effective
interaction between two defects is investigated. All results should be
experimentally observable in thin sheets of colloidal liquid crystals.Comment: 13 pages, 16 figures, Phys. Rev.
Sudden switch of generalized Lieb-Robinson velocity in a transverse field Ising spin chain
The Lieb-Robinson theorem states that the speed at which the correlations
between two distant nodes in a spin network can be built through local
interactions has an upper bound, which is called the Lieb-Robinson velocity.
Our central aim is to demonstrate how to observe the Lieb-Robinson velocity in
an Ising spin chain with a strong transverse field. We adopt and compare four
correlation measures for characterizing different types of correlations, which
include correlation function, mutual information, quantum discord, and
entanglement of formation. We prove that one of correlation functions shows a
special behavior depending on the parity of the spin number. All the
information-theoretical correlation measures demonstrate the existence of the
Lieb-Robinson velocity. In particular, we find that there is a sudden switch of
the Lieb-Robinson speed with the increasing of the number of spin
Optimally combining dynamical decoupling and quantum error correction
We show how dynamical decoupling (DD) and quantum error correction (QEC) can
be optimally combined in the setting of fault tolerant quantum computing. To
this end we identify the optimal generator set of DD sequences designed to
protect quantum information encoded into stabilizer subspace or subsystem
codes. This generator set, comprising the stabilizers and logical operators of
the code, minimizes a natural cost function associated with the length of DD
sequences. We prove that with the optimal generator set the restrictive
local-bath assumption used in earlier work on hybrid DD-QEC schemes, can be
significantly relaxed, thus bringing hybrid DD-QEC schemes, and their
potentially considerable advantages, closer to realization.Comment: 6 pages, 1 figur
Predicting volume of distribution with decision tree-based regression methods using predicted tissue:plasma partition coefficients
Background: Volume of distribution is an important pharmacokinetic property that indicates the extent of a drug's distribution in the body tissues. This paper addresses the problem of how to estimate the apparent volume of distribution at steady state (Vss) of chemical compounds in the human body using decision tree-based regression methods from the area of data mining (or machine learning). Hence, the pros and cons of several different types of decision tree-based regression methods have been discussed. The regression methods predict Vss using, as predictive features, both the compounds' molecular descriptors and the compounds' tissue:plasma partition coefficients (Kt:p) - often used in physiologically-based pharmacokinetics. Therefore, this work has assessed whether the data mining-based prediction of Vss can be made more accurate by using as input not only the compounds' molecular descriptors but also (a subset of) their predicted Kt:p values. Results: Comparison of the models that used only molecular descriptors, in particular, the Bagging decision tree (mean fold error of 2.33), with those employing predicted Kt:p values in addition to the molecular descriptors, such as the Bagging decision tree using adipose Kt:p (mean fold error of 2.29), indicated that the use of predicted Kt:p values as descriptors may be beneficial for accurate prediction of Vss using decision trees if prior feature selection is applied. Conclusions: Decision tree based models presented in this work have an accuracy that is reasonable and similar to the accuracy of reported Vss inter-species extrapolations in the literature. The estimation of Vss for new compounds in drug discovery will benefit from methods that are able to integrate large and varied sources of data and flexible non-linear data mining methods such as decision trees, which can produce interpretable models. Figure not available: see fulltext. © 2015 Freitas et al.; licensee Springer
Permutationally invariant state reconstruction
Feasible tomography schemes for large particle numbers must possess, besides
an appropriate data acquisition protocol, also an efficient way to reconstruct
the density operator from the observed finite data set. Since state
reconstruction typically requires the solution of a non-linear large-scale
optimization problem, this is a major challenge in the design of scalable
tomography schemes. Here we present an efficient state reconstruction scheme
for permutationally invariant quantum state tomography. It works for all common
state-of-the-art reconstruction principles, including, in particular, maximum
likelihood and least squares methods, which are the preferred choices in
today's experiments. This high efficiency is achieved by greatly reducing the
dimensionality of the problem employing a particular representation of
permutationally invariant states known from spin coupling combined with convex
optimization, which has clear advantages regarding speed, control and accuracy
in comparison to commonly employed numerical routines. First prototype
implementations easily allow reconstruction of a state of 20 qubits in a few
minutes on a standard computer.Comment: 25 pages, 4 figues, 2 table
The progestational and androgenic properties of medroxyprogesterone acetate: gene regulatory overlap with dihydrotestosterone in breast cancer cells
INTRODUCTION: Medroxyprogesterone acetate (MPA), the major progestin used for oral contraception and hormone replacement therapy, has been implicated in increased breast cancer risk. Is this risk due to its progestational or androgenic properties? To address this, we assessed the transcriptional effects of MPA as compared with those of progesterone and dihydrotestosterone (DHT) in human breast cancer cells. METHOD: A new progesterone receptor-negative, androgen receptor-positive human breast cancer cell line, designated Y-AR, was engineered and characterized. Transcription assays using a synthetic promoter/reporter construct, as well as endogenous gene expression profiling comparing progesterone, MPA and DHT, were performed in cells either lacking or containing progesterone receptor and/or androgen receptor. RESULTS: In progesterone receptor-positive cells, MPA was found to be an effective progestin through both progesterone receptor isoforms in transient transcription assays. Interestingly, DHT signaled through progesterone receptor type B. Expression profiling of endogenous progesterone receptor-regulated genes comparing progesterone and MPA suggested that although MPA may be a somewhat more potent progestin than progesterone, it is qualitatively similar to progesterone. To address effects of MPA through androgen receptor, expression profiling was performed comparing progesterone, MPA and DHT using Y-AR cells. These studies showed extensive gene regulatory overlap between DHT and MPA through androgen receptor and none with progesterone. Interestingly, there was no difference between pharmacological MPA and physiological MPA, suggesting that high-dose therapeutic MPA may be superfluous. CONCLUSION: Our comparison of the gene regulatory profiles of MPA and progesterone suggests that, for physiologic hormone replacement therapy, the actions of MPA do not mimic those of endogenous progesterone alone. Clinically, the complex pharmacology of MPA not only influences its side-effect profile; but it is also possible that the increased breast cancer risk and/or the therapeutic efficacy of MPA in cancer treatment is in part mediated by androgen receptor
Design and Synthesis of High Affinity Inhibitors of Plasmodium falciparum and Plasmodium vivax N-Myristoyltransferases Directed by Ligand Efficiency Dependent Lipophilicity (LELP)
N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both Plasmodium falciparum and P. vivax NMT and displays activity in vivo against a rodent malaria model. Here we describe the discovery of 34c through optimization of a previously described series. Development, guided by targeting a ligand efficiency dependent lipophilicity (LELP) score of less than 10, yielded a 100-fold increase in enzyme affinity and a 100-fold drop in lipophilicity with the addition of only two heavy atoms. 34c was found to be equipotent on chloroquine-sensitive and -resistant cell lines and on both blood and liver stage forms of the parasite. These data further validate NMT as an exciting drug target in malaria and support 34c as an attractive tool for further optimization
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