Rigid Regions Research Articles

Machine Learning to Identify Flexibility Signatures of Class A GPCR Inhibition.

We show that machine learning can pinpoint features distinguishing inactive from active states in proteins, in particular identifying key ligand binding site flexibility transitions in GPCRs that are triggered by biologically active ligands. Our analysis was performed on the helical segments and loops in 18 inactive and 9 active class A G protein-coupled receptors (GPCRs). These three-dimensional (3D) structures were determined in complex with ligands. However, considering the flexible versus rigid state identified by graph-theoretic ProFlex rigidity analysis for each helix and loop segment with the ligand removed, followed by feature selection and k-nearest neighbor classification, was sufficient to identify four segments surrounding the ligand binding site whose flexibility/rigidity accurately predicts whether a GPCR is in an active or inactive state. GPCRs bound to inhibitors were similar in their pattern of flexible versus rigid regions, whereas agonist-bound GPCRs were more flexible and diverse. This new ligand-proximal flexibility signature of GPCR activity was identified without knowledge of the ligand binding mode or previously defined switch regions, while being adjacent to the known transmission switch. Following this proof of concept, the ProFlex flexibility analysis coupled with pattern recognition and activity classification may be useful for predicting whether newly designed ligands behave as activators or inhibitors in protein families in general, based on the pattern of flexibility they induce in the protein.

Spatial Stress of the Pier–Girder Rigid Region of a Continuous Rigid-Frame Bridge with V-Shaped Piers in Two Directions

The pier-girder rigid region of continuous rigid-frame bridges with V-shaped piers has a complex spatial stress state because of its special structure and complex boundary condition. However, using the beam-column element model for mechanical analysis in design induces large errors. Therefore, this study analyzes the spatial stress and structural optimization of the pier-girder rigid region of a continuous rigid-frame bridge with V-shaped piers. A solid model of the pier-girder rigid region is established by photoelastic stress experiment and numerical analysis. The stress distribution characteristics of the pier-girder rigid region in the longest cantilevered stage and operational stage are revealed in view of tri-directional normal stress and boundary tangential normal stress, and the stress distribution curve of slice boundary at key positions is drawn. Results show that (1) the experimental values are consistent with the finite element analysis values, and the compressive stress is dominant in the main girder structure, which meets the design requirements of fully prestressed concrete structures; (2) the tensile stress concentration appears around the hole of the diaphragm in the bridge transverse direction, whereas the compressive stress concentration appears at the joints between the top/bottom plates of the box girder and the diaphragm in the bridge longitudinal direction; (3) the consolidation zone between the V-shaped bracing and the vertical pier is the most dangerous area of the structure, where the structural measurements of increasing the reinforcement or using steel fiber reinforced concrete are proposed. An optimization measure for increasing the height of the vertical pier is introduced to present the property of a flexible pier and optimize the mechanical characteristics of the bridge. As the height of the pier increases, the stress gradient of each section of the V-shaped bracing decreases, and the distribution of cross-section stress becomes uniform. When the height of the pier is greater than five times of the girder height at the pier top, the stress gradient of each section of the V-shaped pier is less than 0.6. Herein, the force is reasonable with large safety reserve, which can adapt to the longitudinal displacement of the main girder caused by concrete shrinkage, creep, and temperature change in the later stage.

The effect of substitution of Sb with Zn on the optical and physical properties of Se90Sb10-xZnx (x = 0, 2, 4, 6, 10 at. %) thin films

In the present study, the effect of substitution of Sb with Zn on the optical properties of Se90Sb10-xZnx (x = 0, 2, 4, 6, 10 at. %) thin films is discussed. Bulk samples are prepared using a conventional melt-quench technique. Amorphous thin films of the compositions are synthesized using thermal evaporation technique. Normal incidence transmission spectra of films is obtained in the spectral range of 400–1100 nm. The envelope method is applied to calculate the refractive index, followed by Cauchy's extrapolation. Spectral distributions of extinction coefficient, absorption coefficient and dielectric loss factor are obtained. Wemple-Didomenico single oscillator model is employed to study refractive index dispersion. The absorption coefficient is of the order of 104 cm−1, and the band-gap is calculated using Tauc’s extrapolation for the indirect transition. The increase in band gap with Zn addition is explained on the basis of chemical bond approach. Topological studies show that the system is in a rigid region The glass transition temperature, mean bond energy and density of the system is also increasing with the increase in Zn content. An effort is made to discuss all the parameters in terms of change in bond length, bond energy and connectedness of the glassy network.

Kinematics of a novel screen surface and parameter optimization for steam coal classification

Dry deep screening plays an important role in the cleaner production of steam coal, increasing the sorting proportion of steam coal and realizing the reduction of the produced slime to prevent environmental pollution. In this study, a rigid-flexible-coupled elastic screen surface (R-FCESS) was proposed for steam coal classification with 3-mm apertures. In addition, the motion trajectory and vibration mode composition of regions on the R-FCESS were investigated by vibration testing technology. The acceleration amplitude on the elastic region of the R-FCESS reached 46.98 m/s2, which was increased by 22.91 m/s2 in comparison with that of the rigid region. The spatio-temporal evolution and distribution of the material bed on the screen surface were analyzed by using a high-speed camera. The projection height of particles in the elastic region was considerably greater than that in the rigid region. Furthermore, the −3 mm classification test of steam coal was carried out, and effects of the excitation force, current frequency, and feed rate on the screening effect were clarified. At an excitation force of 6.43 kN, a current frequency of 48 Hz, and a feed rate of 2.00 kg/s, the screening efficiency and total misplaced material were 89.27% and 5.92%, respectively. Based on the study, a novel process for the separation of steam coal was proposed, leading to the low coal slurry production as well as low pollution.

The role of cold crystallization of homochiral crystallites in the superb heat resistant poly(lactic acid)

AbstractThe superb heat resistance poly(lactic acid) (PLA) were prepared by blending PLA and poly(d‐lactic acid) (PDLA) with various molecular weight (Mn). Formation of the stereocomplex in the blends was confirmed by differential scanning calorimetry and wide‐angle X‐ray diffraction. The results of the heat resistance implied it is possible that elevating the Vicat penetration temperature of PLA up to 150°C by blending with PDLA. The cold crystallization of homochiral crystallites is proven to be the critical factor affecting the heat resistance of PLA. While the PLA or PLA/PDLA blends were heated to cold crystallization temperature of samples, both the crystal content and the rigid amorphous region content are increased due to the cold crystallization and tethering effect, and the stiffness and heat resistance of the sample are improved. The cold crystallization homochiral crystallites kinetics of PLA and PLA/PDLA blends was also studied. The results showed the activation energy (∆E) of cold crystallization increased from 120.30 kJ/mol to 144.66 kJ/mol with the increasing of PDLA content from 2% to 10%.

Single-run HPLC Quantification of Plant Cell Wall Monosaccharides.

The plant cell wall is a complex network of polysaccharides and proteins that provides strength and structural integrity to plant cells, as well as playing a vital role in growth, development, and defense response. Cell wall polysaccharides can be broadly grouped into three categories: cellulose, pectins, and hemicelluloses. Dynamic interactions between polysaccharides and cell wall-associated proteins contribute to regions of flexibility and rigidity within the cell wall, allowing for remodeling when necessary during growth, environmental adaptation, or stress response activation. These polysaccharide interactions are vital to plant growth, however they also contribute to the level of difficulty encountered when attempting to analyze cell wall structure and composition. In the past, lengthy protocols to quantify cell wall monosaccharides contributing to cellulose as well as neutral and acidic cell wall polysaccharides have been used. Recently, a streamlined approach for monosaccharide quantification was described. This protocol combines a simplified hydrolysis method followed by several runs of high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Here, we present an updated version of this protocol in which we can analyze all nine cell wall monosaccharides in a single high-performance liquid chromatography HPAEC-PAD gradient profile. The inclusion of an enzymatic starch degradation, as well as alternate internal standards for added quantification accuracy, and a ready-to-use Python script facilitating data analysis adds a broadened scope of utility to this protocol. This protocol was used to analyze Arabidopsis light-grown seedlings and dark-grown hypocotyls, but is suitable for any plant tissues.

Mechanistic Insights into the Effect of Ligands on Structural Stability and Selectivity of Sulfotransferase 2A1 (SULT2A1).

Cytosolic sulfotransferases (SULTs) acting as phase II metabolic enzymes can be used in the sulfonation of small molecules by transferring a sulfonate group from the unique co-factor 3′-phosphoadenosine 5′-phosphosulfate (PAPS) to the substrates. In the present study, molecular dynamics (MD) simulations and ensemble docking study were employed to theoretically characterize the mechanism for the effect of co-factor (PAP) and ligands (LCA, raloxifene, α-hydroxytamoxifen, ouabain, and 3′-phosphoadenylyl sulfate) on structural stability and selectivity of SULT2A1 from the perspective of the dynamic behavior of SULT2A1 structures. Structural stability and network analyses indicated that the cooperation between PAP and LCA may enhance the thermal stability and compact communication in enzymes. During the MD simulations, the obviously rigid region and inward displacement were detected in the active-site cap (loop16) of the conformation containing PAP, which may be responsible for the significant changes in substrate accessibility and catalytic activity. The smaller substrates such as LCA could bind stably to the active pocket in the presence of PAP. However, the substrates or inhibitors with a large spatial structure needed to bind to the open conformation (without PAP) prior to PAPS binding.

Impact of PEO structure and formulation on the properties of a Lignin/PEO blend

To improve the performance of lignin/PEO fibers as precursors of carbon fibers, blend formulations were designed with an epoxidized PEO and with carbon nanotubes. Model studies demonstrated that the epoxidized PEO could covalently link to lignin. With incorporation of epoxidized PEO, the precursor fibers exhibited enhanced degree of crystallinity of 70 % (52 % without epoxidized PEO) and a doubling of their young modulus (from 200 to 450 MPa) and tensile strength (from 6 to 12 MPa). In contrast, the addition of carbon nanotubes did not impact the morphology nor the mechanical performance of the resulting fibers. It is argued that with its ability to couple lignin to the PEO matrix, epoxidized PEO plays the role of a stress transfer agent between the rigid lignin regions and the flexible PEO regions, thereby improving the blend performance.

Research on Dynamic Characteristics of Rigid-Flexible Coupling System

In order to study the influence of a flexible component on the vibration of a rigid-flexible coupling system under a shooting condition, the finite element theory is used to calculate the modal of the flexible component and establish its rigid region. The dynamic theory is used to establish the system. The virtual prototype is coupled to the virtual prototype, and the virtual prototype is calculated. The vibration displacement of the system under different working conditions is analyzed and discussed. The simulation results show that the flexible component has an influence on the lateral and longitudinal vibration displacement at the muzzle under shooting conditions. The research on the muzzle vibration provides a theoretical basis of the aircraft gun firing accuracy and the overall design of the aircraft.

Lipid Binding Controls Dimerization of the Coat Protein p24 Transmembrane Helix

Coat protein (COP) I and COP II complexes are involved in the transport of proteins between the endoplasmic reticulum and the Golgi apparatus in eukaryotic cells. The formation of COP I/II complexes at membrane surfaces is an early step in vesicle formation and is mastered by p24, a type I transmembrane protein. Oligomerization of p24 monomers was suggested to be mediated and/or stabilized via interactions within the transmembrane domain, and the p24 transmembrane helix appears to selectively bind a single sphingomyelin C18:0 molecule. Furthermore, a potential cholesterol-binding sequence has also been predicted in the p24 transmembrane domain. Thus, sphingomyelin and/or cholesterol binding to the transmembrane domain might directly control the oligomeric state of p24 and, thus, COP vesicle formation. In this study, we show that sequence-specific dimerization of the p24 transmembrane helix is mediated by a LQ7 motif, with Gln187 being of special importance. Whereas cholesterol has no direct impact on p24 dimerization, binding of the sphingolipid can clearly control dimerization of p24 in rigid membrane regions. We suggest that specific binding of a sphingolipid to the p24 transmembrane helix affects p24 dimerization in membranes with increased cholesterol contents. A clearly defined p24 dimerization propensity likely is crucial for the p24 activity, which involves shuttling in between the endoplasmic reticulum and the Golgi membrane, in which cholesterol and SM C18:0 concentrations differ.

Built for Strength: Functional Insights from the Thoracolumbar and Sacrocaudal Regions of the Late Miocene Amphicyonid Magericyon anceps (Carnivora, Amphicyonidae) from Batallones-1 (Madrid, Spain)

We describe and discuss the morphology and functional anatomy of the thoracolumbar and sacrocaudal regions of the vertebral column of the late Miocene amphicyonid Magericyon anceps. These regions are essential for body support, and very relevant for locomotion and prey capture, and thus their study provides interesting insights on the paleobiology and biomechanics of this top predator. Magericyon anceps, the last known amphicyonid in the fossil record of Western Europe, is recorded only from the Vallesian sites of Batallones-1 and Batallones-3 (Madrid, Spain), which have yielded hundreds of fossils of this species, constituting one of the best-known samples of an amphicyonid ever recorded. The morphology of the thoracolumbar region of M. anceps shows some interesting features, such as a characteristic anticlinal region and a powerful and remarkably rigid lumbar region. This suggests that the back of this carnivoran was built for supporting extremely strong tensions that could be generated during different activities, such as running, but these tensions would be more likely suffered when subduing prey during hunting. Also, M. anceps had a long muscular tail, which could be helpful in balancing of various body motions during these activities. In summary, all these features suggest that M. anceps was a powerful predator built for strength, supporting previous hypotheses about the adaptation of this carnivoran to fast killing of prey inhabiting relatively well-vegetated habitats.

A Joint-Based Systematic Wave-Propagation Approach for Forced Vibration Analysis of Large Waveguide Systems

This paper describes an analytical and numerical continuous wave-based approach for the forced vibration analysis of large waveguide systems. With Timoshenko beam theory as the basis for modeling wave propagation in the waveguides, the refraction of waves at discontinuities is studied analytically. Within this context, the refraction of waves at multi-member joints is formulated. In addition, a joint-based procedure is introduced to assemble analytical joint equations in the global system matrix. The joint-based approach is mathematically equivalent with the existing element-based approaches but has the advantage of accounting for the effects of a rigid joint region explicitly. The method is used to find the response of a large frame subjected to steady-state dynamic loadings with a wide range of frequency excitations. The fidelity of the methodology is verified using finite element simulations. The main advantage of the new approach is that it can analyze arbitrary waveguide systems for a wide range of frequencies, which makes it suited for studying the behavior of complex large systems using a single global matrix with a very low computational cost.

Thermoreversible Gelation of a Vinylidene Fluoride‐Based Copolymer in Methyl Ethyl Ketone: Dynamics and Structure

Thermoreversible poly(vinylidene fluoride‐co‐hexafluoropropylene) (P(VDF‐co‐HFP)) gels are formed in an aliphatic ketone − methyl ethyl ketone (MEK) − at high concentrations (above 11 wt%). This gelation phenomenon is first investigated in terms of gelation kinetics which is found to depend strongly on both copolymer concentration and temperature. Melting temperatures Tm of P(VDF‐co‐HFP)‐based gels prepared at different concentrations, in MEK are measured by DSC. Combination of 19F Nuclear Magnetic Resonance (NMR), Small‐Angle X‐ray Scattering (SAXS), and Wide‐Angle X‐ray Scattering (WAXS) on undried/nonlyophilized gels is used to probe both the gelation mechanisms and the structure of these systems. 19F NMR experiments allow studying selectively the fluorinated copolymer. The occurrence of a polymer network‐like structure with rigid zones acting as cross‐links has been highlighted. Such a behavior is only observed in the gel state: no polymer network or rigid zones exist when the polymer–solvent system is in the liquid state. Moreover, the fraction of rigid zones as well as the fraction of elastically active chain portions increases with the copolymer concentration. The nature, of the rigid zones present within the gels are investigated by X‐ray diffraction. Rigid regions are found to display a crystalline order.

Selection and analyses of variants of a designed protein suggest importance of hydrophobicity of partially buried sidechains for protein stability at high temperatures.

Computationally designed proteins of high stability provide specimen in addition to natural proteins for the study of sequence-structure stability relationships at the very high end of protein stability spectrum. The melting temperature of E_1r26, a protein we previously designed using the A Backbone-based Amino aCid Usage Survey (ABACUS) sequence design program, is above 110 °C, more than 50 °C higher than that of the natural thioredoxin protein whose backbone (PDB ID 1R26) has been used as the design target. Using an experimental selection approach, we obtained variants of E_1r26 that remain folded but are of reduced stability, including one whose unfolding temperature and denaturing guanidine concentration are similar to those of 1r26. The mutant unfolds with a certain degree of cooperativity. Its structure solved by X-ray crystallography agrees with that of 1r26 by a root mean square deviation of 1.3 Å, adding supports to the accuracy of the ABACUS method. Analyses of intermediate mutants indicate that the substitution of two partially buried hydrophobic residues (isoleucine and leucine) by polar residues (threonine and serine, respectively) are responsible for the dramatic change in the unfolding temperature. It is suggested that the effects of mutations located in rigid secondary structure regions, but not those in loops, may be well predicted through ABACUS mutation energy analysis. The results also suggest that hydrophobic effects involving intermediately buried sidechains can be critically important for protein stability at high temperatures.

Insights of Pressure‐induced Unfolding of β‐Lactoglobulin as Revealed by Steered Molecular Dynamics

AbstractHigh hydrostatic pressure (HHP) has been widely used in various industries, and the protein as one of the most noticeable bio‐macromolecules has exhibited distinct structural and functional characteristics under HHP conditions. In this work, steered molecular dynamics (SMD) simulations of β‐lactoglobulin (βlg) are exploited to investigate the flexibility of the individual secondary structural element of the polypeptide. The two loops and the two helices on the two sides of the molecular β‐barrel are found to be highly flexible and migrate toward the hydrophobic interior of the protein at relatively low pressures. Interestingly, there is evidence illustrating that water penetrations only occur from the loop‐side of the barrel under pressurizations, which is favored by the enlarged β‐barrel induced through the loop compression. Moreover, increased stability of βlg is attributed to the rigid regions of the protein molecule. N‐ and C‐termini of the polypeptide chain are also found to be of great importance to pressure‐induced unfolding of βlg. It is found the modeling results agree with previous experimental observations, demonstrating the validity of the applications of SMD for studies on pressure‐induced protein unfolding. Such methodology will provide new insight into HHP and be generalized for more complicated systems such as enzymes.

Origin of hardening and universality of cosmic rays spectra in GV–PV rigidity region

Recent balloon-borne and satellite experiments have established new features in the behavior of the spectra of cosmic rays. An analysis of all the data showed that hardening of most abundant primary cosmic ray nuclei spectra with increasing rigidity is observed in > 200 GV region. At the same time, rigidity dependences of secondary cosmic rays are distinctly different. The AMS-02 data show that above 200 GV the secondary cosmic rays Li, Be, B harden more than the primary He, C, O.In this paper we discuss a new scenario that self-consistently describes these new features of the cosmic ray spectra. We demonstrate that the measured by the AMS-02 changes in the slope of the cosmic ray spectra caused by the transition from the contribution of multiple distant Galactic sources, including the nuclear interactions of the particles accelerated by these sources with an interstellar medium during their wandering in the Galaxy, to the contribution of mainly local ones. We also found that the spectral universality is observed at rigidity R > 105 GV.

Aggregated Residual Dilation-Based Feature Pyramid Network for Object Detection

In order to tackle the issue of multi-scale object detection, recent detectors usually adopt hierarchical feature pyramids which are generated by naive combinations of top-down features and lateral features. Considering the limited effective receptive fields of the methods for top-down features augmentation, the generated regions are only associated with the fixed areas of the coarser features. Meanwhile, noisy features are introduced by irrelevant regions inevitably since the finer features in relation to rigid coarser regions. Thus, the pyramidal features with strong semantics are difficult to be obtained via simply enlarging the top-down features. In this paper, we present the Aggregated Residual Dilation based Feature Pyramid Network (ARDFPN) to exploit the inherent correlation of regions in feature pyramid. The network is designed by stacking a building block that aggregates a set of dilated convolutions with the same topology. We show that carefully adding additional transformation stages into feature pyramid enables a potential way for further multi-scale feature generation. As an intuitive extension of Feature Pyramid Network (FPN), we conduct an exhaustive study to evaluate the model performance by replacing FPN with the proposed ARDFPN in both object detection and instance segmentation tasks. With Residual network in Faster R-CNN and Mask R-CNN framework, ARDFPN outperforms the prevalent detection module - FPN on the challenging COCO dataset without bells and whistles. In particular, ARDFPN exhibits a superior performance, especially for the small and middle objects.

Grid generated turbulence under the rigid boundary influence

An experimental investigation was carried out to study the grid generated turbulence and rigid boundary interaction for different mesh size of grid. Quadrant analysis technique was adopted here to provided information on the turbulent bursting events contributing to the Reynolds shear stress at the near rigid boundary region. It was observed that, near the rigid boundary the contribution to the total shear stress due to the ejection and sweeping events changed significantly for larger mesh size. The relative dominance of these two events were found to contribute in a cyclic manner in the near bed region, whereas such phenomenon disappeared in the main flow region. The distribution of the time interval of the ejection and sweeping events were found to change with the change in mesh size of the grid. To characterize the behaviour of eddies, several turbulence scales such as the integral scale, the Kolmogorov microscale, and the Taylor length scales were determined and compared for different mesh size of grids under rigid boundary influence. Integral and Kolmogorov length scales for larger mesh size were less compared to smaller mesh size, which implied that the smaller mesh size reduced the turbulent kinetic energy dissipation at a rate faster than the larger mesh size.

Effect of annealing on microstructure and mechanical properties of polypropylene random copolymer

ABSTRACTIn this work, polypropylene random copolymer (PPR) was taken as an example to study the changes of mechanical properties related to its microstructure evolution. Firstly, the toughness and fracture morphology were analyzed by notched Izod impact test and scanning electron microscope. Annealing at relative lower temperatures (<100°C), mechanical properties are slightly enhanced, which should be pointed out that significant improvements have been observed when annealing at relative higher temperatures (>100°C). Secondly, the study was conducted from the conventional differential scanning calorimetry, wide angle X-ray diffraction, and small-angle X-ray scattering to analyses the changes in the crystalline and amorphous regions. Dynamic thermomechanical analysis was employed to explore the changes of molecular mobility in samples after annealing at different temperatures. Moreover, to find out the stress transfer between the crystalline regions and the amorphous regions, we did further analysis of the typical stress–strain curves and proposed the mechanism of microstructure evolution during annealing process. The results shown that amorphous rearranged and formed thinner lamellae when annealing at relative low temperature. While annealing at higher temperatures, the mobile and rigid amorphous regions rearranged into more perfect lamellae and the density of stress transmitters was increased significantly.

Enhancement of Out‐of‐Plane Hole Mobility in Poly(3‐Hexylthiophene)‐b‐Poly(styrene) Film

AbstractTwo or three orders of higher magnitude out‐of‐plane hole mobilities are observed in the films of poly(3‐hexylthiophene)‐b‐poly(styrene) (P3HT‐b‐PSt) compared with those of P3HT fabricated with the same conditions in a diode geometry. From grazing incidence wide angle X‐ray diffraction analysis, it is found that there is a trend that PSt domains hinder the growth of alkyl stacking, and promote that of the π–π stacking. Differential scanning calorimetry thermogram of P3HT‐b‐PSt exhibits distinct double endothermic peaks, and double glass transitions. The larger change of heat capacity in glass transition at higher temperature indicates that the larger content of rigid amorphous region exists compared with P3HT. It is considered that the higher content of rigid amorphous domain (short‐range ordered packing) interconnects the crystallites (long‐range ordered packing) leading to the extraordinary higher mobility in P3HT‐b‐PSt film.