cgRNASP-CN: a minimal coarse-grained representation-based statistical potential for RNA 3D structure evaluation

Knowledge of RNA 3-dimensional (3D) structures is critical to understand the important biological functions of RNAs, and various models have been developed to predict RNA 3D structures in silico. However, there is still lack of a reliable and efficient statistical potential for RNA 3D structure evaluation. For this purpose, we developed a statistical potential based on a minimal coarse-grained representation and residue separation, where every nucleotide is represented by C4' atom for backbone and N1 (or N9) atom for base. In analogy to the newly developed all-atom rsRNASP, cgRNASP-CN is composed of short-ranged and long-ranged potentials, and the short-ranged one was involved more subtly. The examination indicates that the performance of cgRNASP-CN is close to that of the all-atom rsRNASP and is superior to other top all-atom traditional statistical potentials and scoring functions trained from neural networks, for two realistic test datasets including the RNA-Puzzles dataset. Very importantly, cgRNASP-CN is about 100 times more efficient than existing all-atom statistical potentials/scoring functions including rsRNASP. cgRNASP-CN is available at website: https://github.com/Tan-group/cgRNASP-CN.     

A novel knowledge-based potential for RNA 3D structure evaluation

Ribonucleic acids(RNAs) play a vital role in biology, and knowledge of their three-dimensional(3D) structure is required to understand their biological functions. Recently structural prediction methods have been developed to address this issue, but a series of RNA 3D structures are generally predicted by most existing methods. Therefore, the evaluation of the predicted structures is generally indispensable. Although several methods have been proposed to assess RNA 3D structures, the existing methods are not precise enough. In this work, a new all-atom knowledge-based potential is developed for more accurately evaluating RNA 3D structures. The potential not only includes local and nonlocal interactions but also fully considers the specificity of each RNA by introducing a retraining mechanism. Based on extensive test sets generated from independent methods, the proposed potential correctly distinguished the native state and ranked near-native conformations to effectively select the best. Furthermore, the proposed potential precisely captured RNA structural features such as base-stacking and base-pairing. Comparisons with existing potential methods show that the proposed potential is very reliable and accurate in RNA 3D structure evaluation.     

RNA structure prediction:Progress and perspective

Many recent exciting discoveries have revealed the versatility of RNAs and their importance in a variety of cellular functions which are strongly coupled to RNA structures. To understand the functions of RNAs, some structure prediction models have been developed in recent years. In this review, the progress in computational models for RNA structure prediction is introduced and the distinguishing features of many outstanding algorithms are discussed, emphasizing threedimensional(3D) structure prediction. A promising coarse-grained model for predicting RNA 3D structure, stability and salt effect is also introduced briefly. Finally, we discuss the major challenges in the RNA 3D structure modeling.     

Cloud 3D effects on broadband heating rate profiles: I. Model simulation

Solar broadband heating directly drives the atmospheric and ocean circulations, and is largely determined by cloud spatial 3-diminesional (3D) structures. To study the cloud 3D effects on radiation, a 3D broadband Monte-Carlo radiative transfer model, along with an Independent Pixel/Column Approximation (IPA) method, is used to simulate radiation and heating rate of three typical cloud fields generated by cloud resolving models (CRM). A quantitative and statistical estimation of cloud 3D effects has been developed to investigate the impact of cloud 3D structures on both heating rate strength, STD_Bias, and vertical distribution, CorrCoef. The cloud 3D structures affect some clouds more in heating rate strength and others more in vertical distribution. It is crucial to use the combination of CorrCoef and STD_Bias for better quantitative evaluation of the 3D effects. Furthermore, there is no simple way to define a critical resolution (or average radius), within which the IPA heating rate profiles closely represent the true 3D heating rate profiles. The critical radius (or resolution) strongly depends on solar incident angle as well as cloud vertical distribution. Also, the critical radii for clear-sky columns are larger than for cloudy columns, although the corresponding STD_Bias for clear-sky columns are smaller than for cloudy columns. Analysis based on two different statistical average methods illustrates that the cloud 3D effects due to the dimensionality difference between the 3D clouds (circle average) and 2D clouds (line average) significantly impact on the heating rate profiles.     

Force-constant-decayed anisotropic network model: An improved method for predicting RNA flexibility

RNA is an important biological macromolecule, which plays an irreplaceable role in many life activities. RNA functions are largely determined by its tertiary structure and the intrinsic dynamics encoded in the structure. Thus, how to effective extract structure-encoded dynamics is of great significance for understanding RNA functions. Anisotropic network model (ANM) is an efficient method to investigate macromolecular dynamical properties, which has been widely used in protein studies. However, the performance of the conventional ANM in describing RNA flexibility is not as good as that on proteins. In this study, we proposed a new approach, named force-constant-decayed anisotropic network model (fcd-ANM), to improve the performance in investigating the dynamical properties encoded in RNA structures. In fcd-ANM, nucleotide pairs in RNA structure were connected by springs and the force constant of springs was decayed exponentially based on the separation distance to describe the differences in the inter-nucleotide interaction strength. The performance of fcd-ANM in predicting RNA flexibility was evaluated using a non-redundant structure database composed of 51 RNAs. The results indicate that fcd-ANM significantly outperforms the conventional ANM in reproducing the experimental B-factors of nucleotides in RNA structures, and the Pearson correlation coefficient between the predicted and experimental nucleotide B-factors was distinctly improved by 21.05% compared to the conventional ANM. Fcd-ANM can serve as a more effective method for analysis of RNA dynamical properties.     

Automatic assignment of NOESY cross peaks and determination of the protein structure of a new world scorpion neurotoxin using NOAH/DIAMOD

The 3D NMR structures of the scorpion neurotoxin, CsE-v5, were determined from the same NOESY spectra with NOAH/DIAMOD, an automated assignment and 3D structure calculation software package, and with a conventional manual assignment combined with a distance geometry/simulated annealing (X-PLOR) refinement method. The NOESY assignments and the 3D structures obtained from the two independent methods were compared in detail. The NOAH/DIAMOD program suite uses feedback filtering and self-correcting distance geometry methods to automatically assign NOESY spectra and to calculate the 3D structure of a protein. NOESY cross peaks were automatically picked using a standard software package and combined with 74 manually assigned NOESY peaks to start the NOAH/DIAMOD calculations. After 63 NOAH/DIAMOD cycles, using REDAC procedures in the last 8 cycles, and final FANTOM constrained energy minimization, a bundle of 20 structures with the smallest target functions has a RMSD of 0.81 A for backbone atoms and 1.11 A for all heavy atoms to the mean structure. Despite some missing chemical shifts of side chain protons, 776 (including 74 manually assigned) of 1130 NOE peaks were unambiguously assigned, 150 peaks have more than one possible assignment compatible with the bundle structures, and only 30 peaks could not be assigned within the given chemical shift tolerance ranges in either the D1 or the D2 dimension. The remaining 174, mainly weak NOE peaks were not compatible with the final 20 best bundle structures at the last NOAH/DIAMOD cycle. The automatically determined structures agree well with the structures determined independently using the conventional method and the same NMR spectra, with the mean RMSD in well-defined regions of 0.84 A for bb and 1.48 A for all heavy atoms from residues 2-5, 18-26, 32-36, and 39-45. This study demonstrates the potential of the NOAH/DIAMOD program suite to automatically assign NMR data for proteins and determine their structure.     

STM/STS investigation of edge structure in epitaxial graphene

In this paper, we have used low temperature scanning tunneling microscopy and spectroscopy (LT-STM/STS) to study zigzag or armchair edges of epitaxial graphene on 6H-SiC (0001). The monolayer carbon structures exhibit occasionally one-dimensional ridge (1D) in close vicinity to step edge. This ridge exhibits different edges orientations in armchair–zigzag transition which give rise to different local density of states (LDOS) along this 1D structure. This ridge formation is likely explained by residual compressive in-plane stresses.     

Three-dimensional electromagnetic band-gap structure containing TiO2 fabricated by rapid-prototyping

Three-dimensional (3D) diamond structure electromagnetic band-gap (EBG) structures containing TiO₂ fabricated by rapid-prototyping (RP) technique were investigated. The simulations based on finite element method (FEM) were employed to model the band structures. The influence of aspect ratio on the band gap width was studied. The optimal band gap width EBGs were fabricated and investigated experimentally. Gel-casting together with RP technique were used in the fabrication. TiO₂ gel was cast into the diamond structure molds fabricated by RP method to obtain the green EBG structures. The transmission characteristics of the EBG structures were measured by transmission/reflection (T/R) methods using a vector network analyzer. Complete band-gap was observed in the transmission characteristics in the frequency from 11 GHz to 12 GHz, which agreed well with the simulation results.     

Generation of three-dimensional optical structures by dynamic holograms displayed on a twisted nematic liquid crystal display

Reconstruction of computer generated holograms (CGHs) addressed on a spatial light modulator (SLM) is an effective way to dynamically generate designed light field distributions. Based on the classic Gerchberg–Saxton (GS) algorithm, we proposed a technique, which can greatly reduce the computation cost to about 60 % in calculating CGHs for three-dimensional (3D) structures but with little degradation of reconstructed light field compared with the classic GS algorithm. The CGHs calculated by our method were displayed on a twisted nematic liquid crystal display, working as a phase-only-modulation SLM, and 3D structures of optical fields, e.g., 3D array of optical traps and vortices, were reconstructed with high efficiency and high quality. Besides, the possibility for 3D holographic display or projection was also demonstrated with this algorithm by reconstruction several images simultaneously in distinct axial planes.     

MRI-based biomechanical imaging: initial study on early plaque progression and vessel remodeling

The goal of the study is to develop a noninvasive magnetic resonance imaging (MRI)-based biomechanical imaging technique to address biomechanical pathways of atherosclerotic progression and regression in vivo using a 3D fluid-structure interaction (FSI) model. Initial in vivo study was carried out in an early plaque model in pigs that underwent balloon-overstretch injury to the left carotid arteries. Consecutive MRI scans were performed while the pigs were maintained on high cholesterol (progression) or normal chow (regression), with an injection of a plaque-targeted contrast agent, Gadofluorine M. At the end of study, the specimens of carotid arterial segments were dissected and underwent dedicated mechanical testing to determine their material properties. 3D FSI computational model was applied to calculate structure stress and strain distribution. The plaque structure resembles early plaque with thickened intima. Lower maximal flow shear stress correlates with the growth of plaque volume during progression, but not during regression. In contrast, maximal principle structure stress/stain (stress-P1 and strain-P1) were shown to correlate strongly with the change in the plaque dimension during regression, but moderately during progression. This MRI-based biomechanical imaging method may allow for noninvasive dynamic assessment of local hemodynamic forces on the development of atherosclerotic plaques in vivo.     

Electronic and magnetic structures of chain structured iron selenide compounds

Electronic and magnetic structures of iron selenide compounds Ce2O2FeSe2 （2212＊） and BaFe2Se3 （123＊） are studied by the first-principles calculations. We find that while all these compounds are composed of one-dimensional （1D） Fe chain （or ladder） structures, their electronic structures are not close to be quasi-lD. The magnetic exchange couplings between two nearest-neighbor （NN） chains in 2212＊ and between two NN two-leg-ladders in 123＊ are both antiferromagnetic （AFM）, which is consistent with the presence of significant third NN AFM coupling, a common feature shared in other iron-chalcogenides, FeTe （11＊） and KyFe2-xSe2 （122＊）. In magnetic ground states, each Fe chain of 2212＊ is ferromagnetic and each two-leg ladder of 123＊ form a block-AFM structure. We suggest that all magnetic structures in iron-selenide compounds can be unified into an extended J1-J2-J3 model. Spin-wave excitations of the model are calculated and can be tested by future experiments on these two systems.     

Three-dimensional planarized diffraction structures based on surface relief gratings in azobenzene materials

The method of step-by-step formation of correlated 3D phase optical structures is presented. Surface relief gratings (SRG) recorded in azobenzene polymer layers are alternated with layers of a spacer polymer with a different refractive index. A pair of azobenzene and spacer polymers with excellent compatibility makes it possible to prepare layers of good optical quality in a stack without destruction of SRG in the previous layer. A correlated stack of six layers (three active and three spacer layers) with 2D structures of different types (linear, tetragonal, and hexagonal) were built. In this way hierarchical 3D structures with different grating periods or different shapes of SRG can be also produced, resulting in full flexibility of the structure type and grating parameters.     

全向入射条件下一维固流周期结构中低频声裂隙变化特性研究

利用传递矩阵法, 从理论上建立了全向入射条件下一维固-流周期结构中的声传播模型, 在此基础上计算、分析并比较了无限周期结构的声能带结构和有限周期结构中的声传输特性. 研究结果表明, 当声波以一定的入射角入射时, 固-流周期结构的低频通带区域存在一个声裂隙, 该声裂隙所对应的入射角大小与构成周期结构的固体层和流体层的密度或结构尺寸无关, 而仅取决于构成该周期性结构材料的波速. 关键词： 传递矩阵 全向入射 固-流周期结构 声裂隙     

Efficient delivery of Cre-recombinase to neurons in vivo and stable transduction of neurons using adeno-associated and lentiviral vectors

Background

As development proceeds the human embryo attains an ever more complex three dimensional (3D) structure. Analyzing the gene expression patterns that underlie these changes and interpreting their significance depends on identifying the anatomical structures to which they map and following these patterns in developing 3D structures over time. The difficulty of this task greatly increases as more gene expression patterns are added, particularly in organs with complex 3D structures such as the brain. Optical Projection Tomography (OPT) is a new technology which has been developed for rapidly generating digital 3D models of intact specimens. We have assessed the resolution of unstained neuronal structures within a Carnegie Stage (CS)17 OPT model and tested its use as a framework onto which anatomical structures can be defined and gene expression data mapped.

Results

Resolution of the OPT models was assessed by comparison of digital sections with physical sections stained, either with haematoxylin and eosin (H&E) or by immunocytochemistry for GAP43 or PAX6, to identify specific anatomical features. Despite the 3D models being of unstained tissue, peripheral nervous system structures from the trigeminal ganglion (~300 μm by ~150 μm) to the rootlets of cranial nerve XII (~20 μm in diameter) were clearly identifiable, as were structures in the developing neural tube such as the zona limitans intrathalamica (core is ~30 μm thick). Fourteen anatomical domains have been identified and visualised within the CS17 model. Two 3D gene expression domains, known to be defined by Pax6 expression in the mouse, were clearly visible when PAX6 data from 2D sections were mapped to the CS17 model. The feasibility of applying the OPT technology to all stages from CS12 to CS23, which encompasses the major period of organogenesis for the human developing central nervous system, was successfully demonstrated.

Conclusion

In the CS17 model considerable detail is visible within the developing nervous system at a minimum resolution of ~20 μm and 3D anatomical and gene expression domains can be defined and visualised successfully. The OPT models and accompanying technologies for manipulating them provide a powerful approach to visualising and analysing gene expression and morphology during early human brain development.     

Volume quantification by fuzzy logic modelling in freehand ultrasound imaging

Introduction

Many algorithms exist for 3D reconstruction of data from freehand 2D ultrasound slices. These methods are based on interpolation techniques to fill the voxels from the pixels. For quantification purposes, segmentation is involved to delineate the structure of interest. However, speckle and partial volume effect errors can affect quantification.

Objective

This study aimed to assess the effect of the combination of a fuzzy model and 3D reconstruction algorithms of freehand ultrasound images on these errors.

Methods

We introduced a fuzzification step to correct the initial segmentation, by weighting the pixels by a distribution function, taking into account the local gray levels, the orientation of the local gradient, and the local contrast-to-noise ratio. We then used two of the most wide-spread reconstruction algorithms (pixel nearest neighbour (PNN) and voxel nearest neighbour (VNN)) to interpolate and create the volume of the structure. Finally, defuzzification was used to estimate the optimal volume.

Validation

B-scans were acquired using 5 MHz and 8 MHz ultrasound probes on ultrasound tissue-mimicking phantoms. Quantitative evaluation of the reconstructed structures was done by comparing the method output to the real volumes. Comparison was also done with classical PNN and VNN algorithms.

Results

With the fuzzy model quantification errors were less than 4.3%, whereas with classical algorithms, errors were larger (10.3% using PNN, 17.2% using VNN). Furthermore, for very small structures (0.5 cm³), errors reached 24.3% using the classical VNN algorithm, while they were about 9.6% with the fuzzy VNN model.

Conclusion

These experiments prove that the fuzzy model allows volumes to be determined with better accuracy and reproducibility, especially for small structures (<3 cm³).     

Electronic band structures of low-dimensional adsorbate systems: Rare-gas adsorption on transition metals

Angle-resolved photoemission data are dis-cussed for five different Xe adlayers which exhibit electronic structures of different dimensionalities. Xe adsorption on Ni (110)-(1 × 2)-3Hand the (×) R30^° Xe layer on Ru (001) reveal two-dimensional (2D) Xe-derived band structures that are characteristic for hexagonal rare-gas layers. Different Xe 5p dispersion widths on Ni and on Ru are found due to the difference in the Xe-Xe nearest-neighbor distance. For three rare-gas systems (two different Xe coverages on hydrogen-modified Pt (110)-(1 × 2)-H and Kr step decoration on a Pt (997) surface) true one-dimensional (1D) band structures are found. For Xe step adsorption on Pt (997), electronic localized (0D) behavior is observed due to an enlarged Xe-Xe separation. The qualitative differences of the band structures in the case of 2D, 1D and 0D rare-gas systems are demonstrated and are explained by the different dimensionalities of the various structures. Received: 3 August 2000 / Accepted: 4 August 2000 / Published online: 7 March 2001     

Quasi 3D imaging of DNA-gold nanoparticle tetrahedral structures

Verification by imaging of the structure of 3D DNA constructs, both bare and conjugated to metal nanoparticles, is challenging. We demonstrate here two transmission electron microscopy (TEM) based methods to distinguish between fully formed tetrahedra, synthesized from DNA conjugated with gold nanoparticles (GNPs) at their vertices, and structures which are only partially formed. When deposited on a surface, fully formed tetrahedra are expected to retain their 3D pyramidal structure, while partially formed structures are expected to form a 2D structure. The first method by which 3D and 2D structures were distinguished was imaging them at different defocusing values. While for 2D structures all the four GNPs acquire Fresnel fringes at the same defocusing value, for 3D structures at least one particle is at a different plane with respect to the others, and so it acquires Fresnel fringes at a different defocusing value. The second method we show is imaging of the structures at different angles. While a single TEM image gives only a 2D projection of the structure, by combining information achieved from imaging at several tilting angles one may verify the structural construct.     

Motion predicted online dynamic MRI reconstruction from partially sampled k-space data

In this work we address the problem of reconstructing dynamic MRI sequences in an online fashion, i.e. reconstructing the current frame given that the previous frames have been already reconstructed. The reconstruction consists of a prediction and a correction step. The prediction step is based on an Auto-Regressive AR(1) model. Assuming that the prediction is good, the difference between the predicted frame and the actual frame (to be reconstructed) will be sparse. In the correction step, the difference between the predicted frame and the actual frame is estimated from partially sampled K-space data via a sparsity promoting least squares minimization problem. We have compared the proposed method with state-of-the-art methods in online dynamic MRI reconstruction. The experiments have been carried out on 2D and 3D Dynamic Contrast Enhanced (DCE) MRI datasets. Results show that our method yields the least reconstruction error.     

Model for folding and aggregation in RNA secondary structures

We study the statistical mechanics of RNA secondary structures designed to have an attraction between two different types of structures as a model system for heteropolymer aggregation. The competition between the branching entropy of the secondary structure and the energy gained by pairing drives the RNA to undergo a "temperature independent" second order phase transition from a molten to an aggregated phase. The aggregated phase thus obtained has a macroscopically large number of contacts between different RNAs. The partition function scaling exponent for this phase is theta approximately 1/2 and the crossover exponent of the phase transition is nu approximately 5/3. The relevance of these calculations to the aggregation of biological molecules is discussed.     

Three-dimensional isotropic metamaterial consisting of domain-structure

Whether an artificially designed negative-index structure could be regarded as a homogeneous medium or not rests with the ratio of its structural unit (man-made atom) over the operation wavelength. However, this definition is ambiguous, and usually the ratio is too large to rigorously meet the effective medium theory. In this paper a three-dimensional (3D) isotropic structure is presented which is obtained from a two-dimensional (2D) isotropic structure rotating on its axis for a circle, and the material is silver. Numerical studies confirm that both the 2D and 3D structures can realize a negative refractive index at microwave wavelengths. Observing the monitored surface current distributions and analogizing the molecular current and the magnetic domain, we suggest a new concept of domain-structure to explain the interior structure of this metamaterial, and finally conclude that the 3D structure is a kind of domain-structured and isotropic metamaterial.