This paper focuses mainly on developing single-step explicit integration algorithms considering the implicit treatment of velocity. A novel explicit algorithm (GSSI) is proposed and recommended as a ...self-starting dissipative alternative to the central difference methods in transient analysis. GSSI not only shares the same advantages as the central difference methods, such as second-order accuracy and computational cost, but also achieves flexible dissipation control and self-starting property. Remarkably, GSSI provides a significantly larger stability bound than the central difference methods in the damped case. GSSI imposes two algorithmic parameters (
ρ
s
and
ρ
b
) to flexibly adjust numerical dissipation at the bifurcation point. In general, the
ρ
b
controls numerical dissipation at the bifurcation point, while the
ρ
s
further adjusts the amount of dissipation in the low-frequency range. Spectral analysis and numerical examples are given solved to show the superiority of GSSI over the existing single-step explicit methods with respect to accuracy, stability, and dissipation control.
Patterns of interacting amino acids are so preserved within protein families that the sole analysis of evolutionary comutations can identify pairs of contacting residues. It is also known that ...evolution conserves functional dynamics, i.e., the concerted motion or displacement of large protein regions or domains. Is it, therefore, possible to use a pure sequence-based analysis to identify these dynamical domains? To address this question, we introduce here a general coevolutionary coupling analysis strategy and apply it to a curated sequence database of hundreds of protein families. For most families, the sequence-based method partitions amino acids into a few clusters. When viewed in the context of the native structure, these clusters have the signature characteristics of viable protein domains: They are spatially separated but individually compact. They have a direct functional bearing too, as shown for various reference cases. We conclude that even large-scale structural and functionally related properties can be recovered from inference methods applied to evolutionary-related sequences. The method introduced here is available as a software package and web server (spectrus.sissa.it/spectrusevo webserver).
State of the art machine tool controllers offer several Internet-of-Things (IoT) interfaces for machine data acquisition using industrial or edge computers. However, the available data exchange rates ...for these communication platforms are limited to a few hundred Hertz. As the data is not available in high frequency resolution, such a network communication is not suitable for monitoring and optimizing highly dynamic machining processes. This paper describes an efficient system architecture, which enables the acquisition of internal machine data as well as the high frequency sampling of external sensors. Based on this data, an Operational Modal Analysis (OMA) approach can be used to determine the tool tip dynamics during the machining process. Identification of tool tip frequency response requires the reconstruction of the excitation of the machine tool structure, i.e. the occurring machining forces. For this purpose, an approach relying on monitoring the commanded motor currents is applied.
Assembly of KU and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) at DNA double strand breaks (DSBs) forms DNA-PK holoenzyme as a critical initiating step for non-homologous end joining ...(NHEJ) repair of DSBs produced by radiation and chemotherapies. Advanced cryo-electron microscopy (cryo-EM) imaging together with breakthrough macromolecular X-ray crystal (MX) structures of KU and DNA-PKcs recently enabled visualization of the ∼600 kDa DNA-PK assembly at near atomic resolution. These important static structures provide the foundation for definition and interpretation of functional movements crucial to mechanistic understanding that can be tested through solution state structure analysis. We herein therefore leverage Cryo-EM and MX structures for the interpretation of synchrotron small-angle X-ray scattering (SAXS) data on DNA-PK conformations in solution to inform the structural mechanism for NHEJ initiation. SAXS, which measures thermodynamic solution-state conformational states and assemblies outside of cryo- and solid-state conditions, unveils the inherent flexibility of KU, DNA-PKcs and DNA-PK. The combined structural measurements reveal mobility of KU80 C-terminal region (KU80CTR), motion/plasticity of HEAT (DNA-PKcs Huntingtin, Elongation Factor 3, PP2 A, and TOR1) regions, allosteric switching upon DNA-PKcs autophosphorylation, and dimeric arrangements of DNA-PK assembly. Importantly, the results uncover displacement of the N-terminal HEAT domain during autophosphorylation as suitable for a regulated release mechanism of DNA-PKcs from DNA-PK to control unproductive access to toxic and mutagenic DNA repair intermediates. These integrated analyses show that the marriage of SAXS with cryo-EM leverages the strengths of both techniques to enable assessment of functional conformations and flexibility defining atomic-resolution molecular mechanisms for DSB repair.
Pulse-width modulation (PWM) is widely used in motor control and represents a carrier-frequency-dependent structural excitation. The PWM’s excitation harmonics are also reflected in an air gap’s ...electromagnetic forces, the transmitted bearing forces and the resulting structure–borne noise. Inappropriate carrier-frequency selection can cause additional electromagnetic noise. The latter can be reduced by a characterization of the coupling between the excitation harmonics and the structural dynamics. To obtain a clear insight into the physical phenomenon, an experiment with original motor parts is proposed, which introduces bearing force measurement and excludes the aerodynamic and mechanical sources of noise. The detailed dependence of the structure-borne noise on the PWM carrier frequency can be obtained by dense carrier-frequency measurements. The experimental results show that even at higher frequencies (above 10 kHz), the carrier-frequency selection can cause a 25 dB(A) difference in the total sound pressure level. The switching noise of PWM controlled machines can be reduced by the appropriate carrier-frequency selection in accordance with the structural dynamics.
Summary
A novel model order reduction scheme for nonlinear finite element (NL‐FE) structural dynamics models is proposed in this work, which enables an overall accelerated model evaluation. The ...proposed multi‐expansion modal (MEM) reduction employs a set of modal bases evaluated for a number of representative statically deformed configurations, combined with these static deformation patterns, to obtain a reduced order basis (ROB). This ROB is then exploited in an a priori element sampling to obtain a hyper‐reduced model based on the energy‐conserving sampling and weighting approach. The proposed element sampling scheme uses a nonnegative L1 optimization of the element weights where an equality between the projected and hyper‐reduced linearized stiffness matrix or static deformation forces is added. A procedure and several guidelines on the reduced order model setup and evaluation are presented, with specific attention to how the presented approach allows to exploit existing NL‐FE frameworks. The MEM approach is validated numerically on an academic cantilever beam model and is shown to provide good accuracy and consistent convergence properties.
Integrins are heterodimeric cell-adhesion receptors comprising α and β subunits that transmit signals allosterically in both directions across the membrane by binding to intra- and extracellular ...components. The human platelet antigen-1 (HPA-1) polymorphism in αIIbβ3 arises from a Leu → Pro exchange at residue 33 in the genu of the β3 subunit, resulting in Leu33 (HPA-1a) or Pro33 (HPA-1b) isoforms. Although clinical investigations have provided conflicting results, some studies have suggested that Pro33 platelets exhibit increased thrombogenicity. Under flow-dynamic conditions, the Pro33 variant displays prothrombotic properties, characterized by increased platelet adhesion, aggregate/thrombus formation, and outside-in signaling. However, the molecular events underlying this prothrombotic phenotype have remained elusive. As residue 33 is located >80 Å away from extracellular binding sites or transmembrane domains, we hypothesized that the Leu → Pro exchange allosterically shifts the dynamic conformational equilibrium of αIIbβ3 toward an active state. Multiple microsecond-long, all-atom molecular dynamics simulations of the ectodomain of the Leu33 and Pro33 isoforms provided evidence that the Leu → Pro exchange weakens interdomain interactions at the genu and alters the structural dynamics of the integrin to a more unbent and splayed state. Using FRET analysis of fluorescent proteins fused with αIIbβ3 in transfected HEK293 cells, we found that the Pro33 variant in its resting state displays a lower energy transfer than the Leu33 isoform. This finding indicated a larger spatial separation of the cytoplasmic tails in the Pro33 variant. Together, our results indicate that the Leu → Pro exchange allosterically shifts the dynamic conformational equilibrium of αIIbβ3 to a structural state closer to the active one, promoting the fully active state and fostering the prothrombotic phenotype of Pro33 platelets.
•Optical flow accurately measured vibrations 450 times smaller than a pixel.•Optimal processing parameters must be chosen to obtain accurate results.•A systematic method of determining the parameter ...values should be researched.
As digital cameras become cheaper and faster, new opportunities for measuring structural vibration are unlocked. Measuring vibration through video sequences can provide full field measurements of a structure’s motion. Digital image correlation is an established method for measuring structural vibration but requires visual surface preparation of the object being measured. Recently, a new method based on optical flow analysis of video sequences has surfaced that can measure structural vibration without any surface preparation whatsoever. This article presents an experiment to test the accuracy of the new method. The accuracy of the technique is evaluated for several sub-pixel vibration displacement amplitudes. The response is measured by an accelerometer, a laser vibrometer and marker tracking and compared to the optical flow method’s results. The results obtained indicate that it is possible to measure vibration amplitudes 450 times smaller than a single image pixel accurately.
Advances of the analytical, numerical, experimental and field-measurement approaches in wind engineering offers unprecedented volume of data that, together with rapidly evolving learning algorithms ...and high-performance computational hardware, provide an opportunity for the community to embrace and harness full potential of machine learning (ML). This contribution examines the state of research and practice of ML for its applications to wind engineering. In addition to ML applications to wind climate, terrain/topography, aerodynamics/aeroelasticity and structural dynamics (following traditional Alan G. Davenport Wind Loading Chain), the review also extends to cover wind damage assessment and wind-related hazard mitigation and response (considering emerging performance-based and resilience-based wind design methodologies). This state-of-the-art review suggests to what extend ML has been utilized in each of these topic areas within wind engineering and provides a comprehensive summary to improve understanding how learning algorithms work and when these schemes succeed or fail. Moreover, critical challenges and prospects of ML applications in wind engineering are identified to facilitate future research efforts.
Many biological functions of peptides are mediated through G protein-coupled receptors (GPCRs). Upon ligand binding, GPCRs undergo conformational changes that facilitate the binding and activation of ...multiple effectors. GPCRs regulate nearly all physiological processes and are a favorite pharmacological target. In particular, drugs are sought after that elicit the recruitment of selected effectors only (biased ligands). Understanding how ligands bind to GPCRs and which conformational changes they induce is a fundamental step toward the development of more efficient and specific drugs. Moreover, it is emerging that the dynamic of the ligand-receptor interaction contributes to the specificity of both ligand recognition and effector recruitment, an aspect that is missing in structural snapshots from crystallography. We describe here biochemical and biophysical techniques to address ligand-receptor interactions in their structural and dynamic aspects, which include mutagenesis, crosslinking, spectroscopic techniques, and mass-spectrometry profiling. With a main focus on peptide receptors, we present methods to unveil the ligand-receptor contact interface and methods that address conformational changes both in the ligand and the GPCR. The presented studies highlight a wide structural heterogeneity among peptide receptors, reveal distinct structural changes occurring during ligand binding and a surprisingly high dynamics of the ligand-GPCR complexes.
PDF
