81 research outputs found
Harmonic emission from cluster nanoplasmas subject to intense short laser pulses
Harmonic emission from cluster nanoplasmas subject to short intense infrared
laser pulses is studied. In a previous publication [M. Kundu et al., Phys. Rev.
A 76, 033201 (2007)] we reported particle-in-cell simulation results showing
resonant enhancements of low-order harmonics when the Mie plasma frequency of
the ionizing and expanding cluster resonates with the respective harmonic
frequency. Simultaneously we found that high-order harmonics were barely
present in the spectrum, even at high intensities. The current paper is focused
on the analytical modeling of the process. We show that dynamical stochasticity
owing to nonlinear resonance inhibits the emission of high order harmonics.Comment: 12 pages, 7 figures, RevTe
Protein Evolution by Molecular Tinkering: Diversification of the Nuclear Receptor Superfamily from a Ligand-Dependent Ancestor
Phylogenetic reconstruction of the structure and function of the ancestor of the nuclear receptor protein family reveals how functional diversity evolves by subtle tinkering with an ancestral template
MiR-137 Targets Estrogen-Related Receptor Alpha and Impairs the Proliferative and Migratory Capacity of Breast Cancer Cells
ERRΞ± is an orphan nuclear receptor emerging as a novel biomarker of breast cancer. Over-expression of ERRΞ± in breast tumor is considered as a prognostic factor of poor clinical outcome. The mechanisms underlying the dysexpression of this nuclear receptor, however, are poorly understood. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level and play important roles in tumor initiation and progression. In the present study, we have identified that the expression of ERRΞ± is regulated by miR-137, a potential tumor suppressor microRNA. The bioinformatics search revealed two putative and highly conserved target-sites for miR-137 located within the ERRΞ± 3β²UTR at nt 480β486 and nt 596β602 respectively. Luciferase-reporter assay demonstrated that the two predicted target sites were authentically functional. They mediated the repression of reporter gene expression induced by miR-137 in an additive manner. Moreover, ectopic expression of miR-137 down-regulated ERRΞ± expression at both protein level and mRNA level, and the miR-137 induced ERRΞ±-knockdown contributed to the impaired proliferative and migratory capacity of breast cancer cells. Furthermore, transfection with miR-137mimics suppressed at least two downstream target genes of ERRΞ±βCCNE1 and WNT11, which are important effectors of ERRΞ± implicated in tumor proliferation and migration. Taken together, our results establish a role of miR-137 in negatively regulating ERRΞ± expression and breast cancer cell proliferation and migration. They suggest that manipulating the expression level of ERRΞ± by microRNAs has the potential to influence breast cancer progression
Homology modelling and spectroscopy, a never-ending love story
Homology modelling is normally the technique of choice when experimental structure data are not available but three-dimensional coordinates are needed, for example, to aid with detailed interpretation of results of spectroscopic studies. Herein, the state of the art of homology modelling will be described in the light of a series of recent developments, and an overview will be given of the problems and opportunities encountered in this field. The major topic, the accuracy and precision of homology models, will be discussed extensively due to its influence on the reliability of conclusions drawn from the combination of homology models and spectroscopic data. Three real-world examples will illustrate how both homology modelling and spectroscopy can be beneficial for (bio)medical research
Active Nuclear Receptors Exhibit Highly Correlated AF-2 Domain Motions
Nuclear receptor ligand binding domains (LBDs) convert ligand binding events into changes in gene expression by recruiting transcriptional coregulators to a conserved activation function-2 (AF-2) surface. While most nuclear receptor LBDs form homo- or heterodimers, the human nuclear receptor pregnane X receptor (PXR) forms a unique and essential homodimer and is proposed to assemble into a functional heterotetramer with the retinoid X receptor (RXR). How the homodimer interface, which is located 30 Γ
from the AF-2, would affect function at this critical surface has remained unclear. By using 20- to 30-ns molecular dynamics simulations on PXR in various oligomerization states, we observed a remarkably high degree of correlated motion in the PXRβRXR heterotetramer, most notably in the four helices that create the AF-2 domain. The function of such correlation may be to create βactive-capableβ receptor complexes that are ready to bind to transcriptional coactivators. Indeed, we found in additional simulations that active-capable receptor complexes involving other orphan or steroid nuclear receptors also exhibit highly correlated AF-2 domain motions. We further propose a mechanism for the transmission of long-range motions through the nuclear receptor LBD to the AF-2 surface. Taken together, our findings indicate that long-range motions within the LBD scaffold are critical to nuclear receptor function by promoting a mobile AF-2 state ready to bind coactivators
On the Practicality of a Family of Pop-Up Parabolic Reflectors
The transformation of doubly curved surfaces, without affecting their geometric integrity, into quasifoldable mechanisms via surface discontinuities is a recently proposed approach to self-deploying ( popup ) reflectors. The marriage of surface accuracy and kinematic simplicity this concept represents may be especially attractive for small satellite antenna applications, once certain questions of practicality are answered. This paper is to summarize these questions and to quantitatively examine one of them - stowage efficiency - in the context of parabolic reflectors. First, a structural classification of deployable antenna dishes is put forth and the concerned pop-up concept is introduced. Some of the mechanical and geometric characteristics of the latter are briefly reviewed next, and the family of deployable reflectors it represents is illustrated via breadboard demonstration models. A brief study follows, wherein the stowage efficiency of the most promising proposed configuration is shown to be competitive with existing technology. This comparison is enabled by the stowage ratio, defined herein as a general measure of stowage efficiency independent of reflector structure and size. Finally, conclusions are drawn and functional, manufacturing, as well as further research issues are summarized
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