Numerical studies of aerofractures in porous media / Estudios numericos de aerofractures en medios porosos

During the hydraulically induced compaction of a granular layer fracture patterns arise. In numerical simulations we study how these patterns depend on the gas properties as well as on the properties of the porous medium. In particular the relation between the speed of fracture propagation and injection pressure is here studied in detail.Comment: Revista Cubana de Fisica, volume following the MarchCoMeeting'12 access on: http://www.fisica.uh.cu/biblioteca/revcubfis/index.php/component/content/article?id=3

Numerical studies of aerofractures in porous media

During the hydraulically induced compaction of a granular layer fracture patterns arise. In numerical simulations we study how these patterns depend on the gas properties as well as on the properties of the porous medium. In particular the relation between the speed of fracture propagation and injection pressure is here studied in detail

Mixing of a granular layer falling through a fluid

We analyze the granular Rayleigh-Taylor instability of densely packed grains immersed in a compressible or an incompressible fluid using numerical simulations and two types of experiments. The simulations are based on a two-dimensional (2D) molecular dynamics model and the experiments have been carried out in systems of grains immersed in water/glycerol (incompressible fluid) and in air (compressible fluid). The variation of the interstitial fluid is shown to generate different dynamical patterns and mixing properties of the granular systems. The results have been quantified using 2D autocorrelation functions, the power spectrum of the velocity field and velocity field histograms. Excellent agreement is found between the numerical simulations and the experiments. © 2010 The American Physical Society

Structural photoactivation of a full-length bacterial phytochrome

Phytochromes are light sensor proteins found in plants, bacteria, and fungi. They function by converting a photon absorption event into a conformational signal that propagates from the chromophore through the entire protein. However, the structure of the photoactivated state and the conformational changes that lead to it are not known. We report time-resolved x-ray scattering of the full-length phytochrome from Deinococcus radiodurans on micro- and millisecond time scales. We identify a twist of the histidine kinase output domains with respect to the chromophore-binding domains as the dominant change between the photoactivated and resting states. The time-resolved data further show that the structural changes up to the microsecond time scales are small and localized in the chromophore-binding domains. The global structural change occurs within a few milliseconds, coinciding with the formation of the spectroscopic meta-Rc state. Our findings establish key elements of the signaling mechanism of full-length bacterial phytochromes

Massive X-ray screening reveals two allosteric drug binding sites of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous health problems and economical challenges for mankind. To date, no effective drug is available to directly treat the disease and prevent virus spreading. In a search for a drug against COVID-19, we have performed a massive X-ray crystallographic screen of repurposing drug libraries containing 5953 individual compounds against the SARS-CoV-2 main protease (Mpro), which is a potent drug target as it is essential for the virus replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds binding to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and five non-peptidic compounds showed antiviral activity at non-toxic concentrations. Interestingly, two compounds bind outside the active site to the native dimer interface in close proximity to the S1 binding pocket. Another compound binds in a cleft between the catalytic and dimerization domain of Mpro. Neither binding site is related to the enzymatic active site and both represent attractive targets for drug development against SARS-CoV-2. This X-ray screening approach thus has the potential to help deliver an approved drug on an accelerated time-scale for this and future pandemics

X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (M^(pro)), which is essential for viral replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to M^(pro). In subsequent cell-based viral reduction assays, one peptidomimetic and six non-peptidic compounds showed antiviral activity at non-toxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2

Sedimentation instabilities: Impact of the fluid compressibility and viscosity: Impact of the fluid compressibility and viscosity

The effect of an interstitial fluid on the mixing of sedimenting grains is studied numerically in a closed rectangular Hele-Shaw cell. We investigate the impact of the fluid compressibility and fluid viscosity on the dynamics and structures of the granular Rayleigh-Taylor instability. First we discuss the effect of the fluid compressibility on the initial fluid pressure evolution and on the dynamics of the particles. Here, the emerging patterns do not seem highly affected by the compressibility change studied. To characterize the patterns and motion the combined length of the particle trajectories in relation to the movement of the center of mass is analyzed, and the separation of particle pairs is measured as a function of the fluid viscosity. © 2010 The American Physical Society

Structural photoactivation of a full-length bacterial phytochrome

Phytochromes are light sensor proteins found in plants, bacteria, and fungi. They function by converting a photon absorption event into a conformational signal that propagates from the chromophore through the entire protein. However, the structure of the photoactivated state and the conformational changes that lead to it are not known. We report time-resolved x-ray scattering of the full-length phytochrome from Deinococcus radiodurans on micro-and millisecond time scales. We identify a twist of the histidine kinase output domains with respect to the chromophore-binding domains as the dominant change between the photoactivated and resting states. The time-resolved data further show that the structural changes up to the microsecond time scales are small and localized in the chromophore-binding domains. The global structural change occurs within a few milliseconds, coinciding with the formation of the spectroscopic meta-Rc state. Our findings establish key elements of the signaling mechanism of full-length bacterial phytochromes