•Using the mathematical formulation of the fourth-order tensor to represent the multilayer networks.•Four metrics are used to quantify nodes and layers in multilayer networks and an iterative ...algorithm is proposed.•Using the theory of multilinear algebra to prove the convergence of the iterative algorithm.•The new centrality measure SVT is applied to two real-world multilayer networks related to cancers.
One challenging issue in information science, biological systems and many other field is to determine the most central agents in multilayer networked systems characterized by different types of interrelationships. In this paper, using a fourth-order tensor to represent multilayer networks, we propose a new centrality measure, referred to as the Singular Vector of Tensor (SVT) centrality, which is used to quantitatively evaluate the importance of nodes connected by different types of links in multilayer networks. First, we present a novel iterative method to obtain four alternative metrics that can quantify the hub and authority scores of nodes and layers in multilayer networked systems. Moreover, we use the theory of multilinear algebra to prove that the four metrics converge to four singular vectors of the adjacency tensor of the multilayer network under reasonable conditions. Furthermore, a novel SVT centrality measure is obtained by integrating these four metrics. The experimental results demonstrate that the proposed method is a new centrality measure that significantly outperforms six other published centrality methods on two real-world multilayer networks related to complex diseases, i.e., gastric and colon cancers.
With the development of multi-constellation multi-frequency Global Navigation Satellite Systems (GNSS), more and more observations are available for tightly coupled GNSS/Inertial Navigation System ...(INS) integration. Concerning the accuracy, robustness, and computational burden issues in the integration, we proposed a robust and computationally efficient implementation. The new tight integration model uses pseudorange, Doppler and carrier phase simultaneously, to achieve the maximum possible navigation accuracy for a single receiver. The resultant high-dimensional observation vector is then processed by a sequential Kalman Filter (KF) to improve the computational efficiency in the measurement update step. Based on the innovation of the sequential KF, a robust estimation method with Gaussian test is further devised to detect and adapt the faults in individual GNSS channels. Two field vehicular tests are conducted to evaluate the performance improvements of the proposed method, compared with loose coupling and conventional tight coupling. Test results in favorable environments indicate that the proposed method can significantly improve the velocity and attitude accuracy by 69.42% and 47.16% over loose coupling and by 64.75% and 30.88% over conventional tight coupling, respectively. Moreover, the computational efficiency is also improved by about 53.09% for the proposed method, compared with batch KF processing. In GNSS challenging environments, the proposed method also shows superiority in terms of velocity and attitude accuracy, and better bridging capability during the GNSS partial or complete outages. These results demonstrate that the proposed method is able to provide a more robust and accurate solution in real-time vehicular navigation.
In this paper, an adaptive unscented Kalman filter for UAV's MEMS-based navigation is derived to realize in-flight initial alignment aided by GNSS (global navigation satellite system) and fulfill ...data fusion. In the filter, unscented transformation is used to handle strong INS (Inertial Navigation System) model nonlinearity under large misalignment condition due to large and sudden maneuvers, and the technique of optimal adaptive factor is used to resist the influence of noise uncertainty of MIMU (MEMS-based Inertial Measurement Unit) and kinematic model errors. The flight test results indicate the proposed alignment algorithm can complete the initial alignment more quickly and accurately compared with the conventional EKF/UKF-based in-motion alignment approaches, especially when the initial attitude errors are large. As a unified in-flight alignment, it can guarantee the accurate and reliable alignment in situations of either large or small initial attitude errors without model changes for small UAV applications.
Several liquid sample injection methods have been developed to satisfy the requirements for serial femtosecond X‐ray nanocrystallography, which enables radiation‐damage‐free determination of ...molecular structure at room temperature. Time‐resolved nanocrystallography would combine structure analysis with chemical kinetics by determining the structures of the transient states and chemical kinetic mechanisms simultaneously. A windowless liquid mixing jet device has been designed for this purpose. It achieves fast uniform mixing of substrates and enzymes in the jet within 250 µs, with an adjustable delay between mixing and probing by the X‐ray free‐electron laser beam of up to 1 s for each frame of a `movie'. The principle of the liquid mixing jet device is illustrated using numerical simulation, and experimental results are presented using a fluorescent dye.
G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent ...pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Angiotensin II type 1 receptor (AT1R) is a G protein-coupled receptor that serves as a primary regulator for blood pressure maintenance. Although several anti-hypertensive drugs have been developed ...as AT1R blockers (ARBs), the structural basis for AT1R ligand-binding and regulation has remained elusive, mostly due to the difficulties of growing high-quality crystals for structure determination using synchrotron radiation. By applying the recently developed method of serial femtosecond crystallography at an X-ray free-electron laser, we successfully determined the room-temperature crystal structure of the human AT1R in complex with its selective antagonist ZD7155 at 2.9-Å resolution. The AT1R-ZD7155 complex structure revealed key structural features of AT1R and critical interactions for ZD7155 binding. Docking simulations of the clinically used ARBs into the AT1R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT1R structure-function relationship and structure-based drug design.
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•Crystal structure of the human Angiotensin II type 1 receptor at 2.9-Å resolution•Structure is solved by X-ray laser serial femtosecond crystallography•Antagonist ZD7155 forms critical interactions with Tyr35, Trp84 and Arg167•Docking reveals binding modes of common angiotensin receptor blockers
Structure determination of human Angiotensin II type 1 receptor bound to an antagonist using serial femtosecond crystallography with X-ray free-electron laser and docking studies of other common anti-hypertensive drugs into the structure offer insights into design of blood pressure modulators.
Appropriate cycle-slip and measurement-error models are essential for BeiDou carrier-phase-based integrity risk calculation. To establish the receiver’s measurement-error model, an accurate position ...reference of the GNSS antenna is fundamental for calculating the measurement error. However, it is still a challenge to acquire position references for dynamic BeiDou receivers, resulting in improper GNSS measurement-error models and unreliable integrity monitoring. This paper proposes an improved precise relative positioning scheme by adopting multi-antenna trajectory constraints for dynamic BeiDou receivers. The dynamic experiments show an obvious decline of 78.7%, at most, in the positioning failure rate of the proposed method, as compared with the traditional method. The position solutions obtained from the proposed approach are used as the reference to analyze the cycle-slip and measurement-error characteristics of the dynamic receiver. The field test results indicate that the cycle-slip rate decreases with the increase of signal-to-noise ratio (SNR), and cycle slipping obeys a positively skewed distribution that could be fitted by the Gaussian mixture model (GMM). On the other hand, the standard deviation of the carrier-phase measurement error is inversely proportional to SNR, and its distribution is characteristically fat-tailed, which could be fitted by the bi-normal model.
Serial femtosecond crystallography using ultrashort pulses from x-ray free electron lasers (XFELs) enables studies of the light-triggered dynamics of biomolecuies. We used microcrystals of ...photoactive yellow protein (a bacterial blue light photoreceptor) as a model system and obtained high-resolution, time-resolved difference electron density maps of excellent quality with strong features; these allowed the determination of structures of reaction intermediates to a resolution of 1.6 angstroms. Our results open the way to the study of reversible and nonreversible biological reactions on time scales as short as femtoseconds under conditions that maximize the extent of reaction initiation throughout the crystal.
Networks have been widely used to model the structures of various biological systems. The ultimate aim of research on biological networks is to steer biological system structures to desired states by ...manipulating signals. Despite great advances in the linear control of single-layer networks, it has been observed that many complex biological systems have a multilayer networked structure and extremely complicated nonlinear processes.
In this study, we propose a general framework for controlling nonlinear dynamical systems with multilayer networked structures by formulating the problem as a minimum union optimization problem. In particular, we offer a novel approach for identifying the minimal driver nodes that can steer a multilayered nonlinear dynamical system toward any desired dynamical attractor. Three disease-related biology multilayer networks are used to demonstrate the effectiveness of our approaches. Moreover, in the set of minimum driver nodes identified by the algorithm we proposed, we confirmed that some nodes can act as drug targets in the biological experiments. Other nodes have not been reported as drug targets; however, they are also involved in important biological processes from existing literature.
The proposed method could be a promising tool for determining higher drug target enrichment or more meaningful steering nodes for studying complex diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Photosynthesis, a process catalysed by plants, algae and cyanobacteria converts sunlight to energy thus sustaining all higher life on Earth. Two large membrane protein complexes, photosystem I and II ...(PSI and PSII), act in series to catalyse the light-driven reactions in photosynthesis. PSII catalyses the light-driven water splitting process, which maintains the Earth's oxygenic atmosphere. In this process, the oxygen-evolving complex (OEC) of PSII cycles through five states, S0 to S4, in which four electrons are sequentially extracted from the OEC in four light-driven charge-separation events. Here we describe time resolved experiments on PSII nano/microcrystals from Thermosynechococcus elongatus performed with the recently developed technique of serial femtosecond crystallography. Structures have been determined from PSII in the dark S1 state and after double laser excitation (putative S3 state) at 5 and 5.5 Å resolution, respectively. The results provide evidence that PSII undergoes significant conformational changes at the electron acceptor side and at the Mn4CaO5 core of the OEC. These include an elongation of the metal cluster, accompanied by changes in the protein environment, which could allow for binding of the second substrate water molecule between the more distant protruding Mn (referred to as the 'dangler' Mn) and the Mn3CaOx cubane in the S2 to S3 transition, as predicted by spectroscopic and computational studies. This work shows the great potential for time-resolved serial femtosecond crystallography for investigation of catalytic processes in biomolecules.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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