Evaluating functions of positive-definite matrices using colored noise thermostats

Many applications in computational science require computing the elements of a function of a large matrix. A commonly used approach is based on the the evaluation of the eigenvalue decomposition, a task that, in general, involves a computing time that scales with the cube of the size of the matrix. We present here a method that can be used to evaluate the elements of a function of a positive-definite matrix with a scaling that is linear for sparse matrices and quadratic in the general case. This methodology is based on the properties of the dynamics of a multidimensional harmonic potential coupled with colored noise generalized Langevin equation (GLE) thermostats. This "$f-$thermostat" (FTH) approach allows us to calculate directly elements of functions of a positive-definite matrix by carefully tailoring the properties of the stochastic dynamics. We demonstrate the scaling and the accuracy of this approach for both dense and sparse problems and compare the results with other established methodologies.Comment: 8 pages, 4 figure

Dissipative cooling induced by pulse perturbations

We investigate the dynamics brought on by an impulse perturbation in two infinite-range quantum Ising models coupled to each other and to a dissipative bath. We show that, if dissipation is faster the higher the excitation energy, the pulse perturbation cools down the low-energy sector of the system, at the expense of the high-energy one, eventually stabilising a transient symmetry-broken state at temperatures higher than the equilibrium critical one. Such non-thermal quasi-steady state may survive for quite a long time after the pulse, if the latter is properly tailore

The effect of scaffold pore size in cartilage tissue engineering

open4noIntroduction: The effect of scaffold pore size and interconnectivity is undoubtedly a crucial factor for most tissue engineering applications. The aim of this study was to examine the effect of pore size and porosity on cartilage construct development in different scaffolds seeded with articular chondrocytes. Methods: We fabricated poly-L-lactide-co-trimethylene carbonate scaffolds with different pore sizes, using a solvent-casting/particulate-leaching technique. We seeded primary bovine articular chondrocytes on these scaffolds, cultured the constructs for 2 weeks and examined cell proliferation, viability and cell-specific production of cartilaginous extracellular matrix proteins, including GAG and collagen. Results: Cell density significantly increased up to 50% with scaffold pore size and porosity, likely facilitated by cell spreading on the internal surface of bigger pores, and by increased mass transport of gases and nutrients to cells, and catabolite removal from cells, allowed by lower diffusion barriers in scaffolds with a higher porosity. However, both the cell metabolic activity and the synthesis of cartilaginous matrix proteins significantly decreased by up to 40% with pore size. We propose that the association of smaller pore diameters, causing 3-dimensional cell aggregation, to a lower oxygenation caused by a lower porosity, could have been the condition that increased the cell-specific synthesis of cartilaginous matrix proteins in the scaffold with the smallest pores and the lowest porosity among those tested. Conclusions: In the initial steps of in vitro cartilage engineering, the combination of small scaffold pores and low porosity is an effective strategy with regard to the promotion of chondrogenesis.openNava, Michele M; Draghi, Lorenza; Giordano, Carmen; Pietrabissa, RiccardoNava, Michele M; Draghi, Lorenza; Giordano, Carmen; Pietrabissa, Riccard

ATP allosterically stabilizes integrin-linked kinase for efficient force generation

Focal adhesions link the actomyosin cytoskeleton to the extracellular matrix regulating cell adhesion, shape, and migration. Adhesions are dynamically assembled and disassembled in response to extrinsic and intrinsic forces, but how the essential adhesion component integrin-linked kinase (ILK) dynamically responds to mechanical force and what role adenosine triphosphate (ATP) bound to this pseudokinase plays remain elusive. Here, we apply force-probe molecular-dynamics simulations of human ILK:alpha-parvin coupled to traction force microscopy to explore ILK mechanotransducing functions. We identify two key salt-bridge-forming arginines within the allosteric, ATP-dependent force-propagation network of ILK. Disrupting this network by mutation impedes parvin binding, focal adhesion stabilization, force generation, and thus migration. Under tension, ATP shifts the balance from rupture of the complex to protein unfolding, indicating that ATP increases the force threshold required for focal adhesion disassembly. Our study proposes a role of ATP as an obligatory binding partner for structural and mechanical integrity of the pseudokinase ILK, ensuring efficient cellular force generation and migration.Peer reviewe

InSAR time series and LSTM model to support early warning detection tools of ground instabilities: mining site case studies

Early alarm systems can activate vital precautions for saving lives and the economy threatened by natural hazards and human activities. Interferometric synthetic aperture radar (InSAR) products generate valuable ground motion data with high spatial and temporal resolutions. Integrating the InSAR products and forecasting models make possible to set up early alarm systems to monitor vulnerable areas. This study proposes a technical support to early warning detection tools of ground instabilities using machine learning and InSAR time series that is capable of forecasting regions affected by potential collapses. A long short-term memory (LSTM) model is tailored to predict ground movements in three forecast ranges (i.e., SAR observations): 3, 4, and 5 multistep. A contribution of the proposed strategy is utilizing adjacent time series to decrease the possibility of falsely detecting safe regions as significant movements. The proposed tool offers ground motion-based outcomes that can be interpreted and utilized by experts to activate early alarms to reduce the consequences of possible failures in vulnerable infrastructures, such as mining areas. Three case studies in Spain, Brazil, and Australia, where fatal incidents happened, are analyzed by the proposed early alert detector to illustrate the impact of chosen temporal and spatial ranges. Since most early alarm systems are site dependent, we propose a general tool to be interpreted by experts for activating reliable alarms. The results show that the proposed tool can identify potential regions before collapse in all case studies. In addition, the tool can suggest an optimum selection of InSAR temporal (i.e., number of images) and spatial (i.e., adjacent measurement points) combinations based on the available SAR images and the characteristics of the study area.Peer ReviewedPostprint (published version

Hydrostatic pressure prevents chondrocyte differentiation through heterochromatin remodeling

Articular cartilage protects and lubricates joints for smooth motion and transmission of loads. Owing to its high water content, chondrocytes within the cartilage are exposed to high levels of hydrostatic pressure, which has been shown to promote chondrocyte identity through unknown mechanisms. Here, we investigate the effects of hydrostatic pressure on chondrocyte state and behavior, and discover that application of hydrostatic pressure promotes chondrocyte quiescence and prevents maturation towards the hyperlrophic state. Mechanistically, hydrostatic pressure reduces the amount of trimethylated H3K9 (K3K9me3)-marked constitutive heterochromatin and concomitantly increases H3K27me3-marked facultative heterochromatin. Reduced levels of H3K9me3 attenuates expression of pre-hypertrophic genes, replication and transcription, thereby reducing replicative stress. Conversely, promoting replicative stress by inhibition of topoisomerase II decreases Sox9 expression, suggesting that it enhances chondrocyte maturation. Our results reveal how hydrostatic pressure triggers chromatin remodeling to impact cell fate and function. This article has an associated First Person interview with the first author of the paper.Peer reviewe

Genetic variability of the 16S rRNA gene of Nocardia brasiliensis, the most common causative agent of actinomycetoma in Latin America and the Caribbean

Mycetoma is a neglected tropical disease (NTD) declared by the World Health Organization (WHO) in 2016. It is characterized by the progressive growth of nodules and granulomatous lesions on the legs, arms, and trunk. It is potentially disfiguring and causes disability or amputations in working-age people from marginalized areas. The causative agents can be fungi (eumycetoma) or actinobacteria (actinomycetoma), the latter being the most common in America and Asia. Nocardia brasiliensis is the most important causal agent of actinomycetoma in the Americas. Taxonomic problems have been reported when identifying this species, so this study aimed to detect the 16S rRNA gene variations in N. brasiliensis strains using an in silico enzymatic restriction technique. The study included strains from clinical cases of actinomycetoma in Mexico, isolated from humans and previously identified as N. brasiliensis by traditional methods. The strains were characterized microscopically and macroscopically, then subjected to DNA extraction and amplification of the 16S rRNA gene by PCR. The amplification products were sequenced, and consensus sequences were constructed and used for genetic identification and in silico restriction enzyme analysis with the New England BioLabs® NEBcutter program. All study strains were molecularly identified as N. brasiliensis; however, in silico restriction analysis detected a diversity in the restriction patterns that were finally grouped and subclassified into 7 ribotypes. This finding confirms the existence of subgroups within N. brasiliensis. The results support the need to consider N. brasiliensis as a complex species

Optimization of femtosecond laser polymerized structural niches to control mesenchymal stromal cell fate in culture.

We applied two-photon polymerization to fabricate 3D synthetic niches arranged in complex patterns to study the effect of mechano-topological parameters on morphology, renewal and differentiation of rat mesenchymal stromal cells. Niches were formed in a photoresist with low auto-fluorescence, which enabled the clear visualization of the fluorescence emission of the markers used for biological diagnostics within the internal niche structure. The niches were structurally stable in culture up to three weeks. At three weeks of expansion in the niches, cell density increased by almost 10-fold and was 67% greater than in monolayer culture. Evidence of lineage commitment was observed in monolayer culture surrounding the structural niches, and within cell aggregates, but not inside the niches. Thus, structural niches were able not only to direct stem cell homing and colony formation, but also to guide aggregate formation, providing increased surface-to-volume ratios and space for stem cells to adhere and renew, respectively