Increase in degraded collagen type II in synovial fluid early in the rabbit meniscectomy model of osteoarthritis

SummaryObjectiveThe objective of this study was to determine whether collagen type II breakdown products in synovial fluid (SF), detected by an enzyme-linked immunoassay, represent a useful marker for early events in osteoarthritis (OA) in the rabbit medial meniscectomy model.DesignComplete medial meniscectomy was performed on the right knee joints of 32 rabbits. Balanced groups of rabbits were then sacrificed at 2, 4, 8, and 12 weeks post-surgery. An additional 8 unoperated and 11 sham-operated animals served as controls. SF lavages were performed on right and left knee joints of the same animals at sacrifice. The proteolytic epitope of type II collagen was monitored using an enzyme-linked immunoassay.ResultsMacroscopically visible surface fibrillation and focal erosions appeared as early as 2 weeks after meniscectomy in the femorotibial joint (P<0.01). OA developed gradually during the later observation period, and then predominantly on the medial tibial plateau and medial femur. Significant histological alterations in cartilage, including a loss of proteoglycans, surface irregularities, and clefts, were detected at 2 weeks after meniscectomy (P<0.01). Collagen type II epitope levels in SF lavage samples were elevated peaking at 2 weeks after meniscectomy (P<0.02). Levels decreased at later time points, but they were still raised at 12 weeks (P≤0.05). Highly significant correlations were found between the SF collagen type II epitope levels and the macroscopic and microscopic scoring results (Spearman rho correlation coefficient, macroscopy—collagen type II epitope r=0.222, P=0.025; microscopy—collagen type II epitope r=0.436, P≤0.01).ConclusionIn this rabbit model of medial meniscectomy, levels of type II collagen fragments in SF appear to provide a useful marker of the early degenerative changes

A review on sparse solutions in optimal control of partial differential equations

In this paper a review of the results on sparse controls for partial differential equations is presented. There are two different approaches to the sparsity study of control problems. One approach consists of taking functions to control the system, putting in the cost functional a convenient term that promotes the sparsity of the optimal control. A second approach deals with controls that are Borel measures and the norm of the measure is involved in the cost functional. The use of measures as controls allows to obtain optimal controls supported on a zero Lebesgue measure set, which is very interesting for practical implementation. If the state equation is linear, then we can carry out a complete analysis of the control problem with measures. However, if the equation is nonlinear the use of measures to control the system is still an open problem, in general, and the use of functions to control the system seems to be more appropriate.This work was partially supported by the Spanish Ministerio de Economía y Competitividad under project MTM2014-57531-P

Using NMF for analyzing war logs

We investigate a semi-automated identification of technical problems occurred by armed forces weapon systems during mission of war. The proposed methodology is based on a semantic analysis of textual information in reports from soldiers (war logs). Latent semantic indexing (LSI) with non-negative matrix factorization (NMF) as technique from multivariate analysis and linear algebra is used to extract hidden semantic textual patterns from the reports. NMF factorizes the term-by-war log matrix - that consists of weighted term frequencies into two non-negative matrices. This enables natural parts-based representation of the report information and it leads to an easy evaluation by human experts because human brain also uses parts-based representation. For an improved research and technology planning, the identified technical problems are a valuable source of information. A case study extracts technical problems from military logs of the Afghanistan war. Results are compared to a manual analysis written by journalists of 'Der Spiegel'

Finite element approximation of sparse parabolic control problems

We study the finite element approximation of an optimal control problem governed by a semilinear partial differential equation and whose objective function includes a term promoting space sparsity of the solutions. We prove existence of solution in the absence of control bound constraints and provide the adequate second order sufficient conditions to obtain error estimates. Full discretization of the problem is carried out, and the sparsity properties of the discrete solutions, as well as error estimates, are obtained.The first two authors were partially supported by the Spanish Ministerio de Economía y Competitividad under project MTM2014-57531-P

PT-symmetric models in curved manifolds

We consider the Laplace-Beltrami operator in tubular neighbourhoods of curves on two-dimensional Riemannian manifolds, subject to non-Hermitian parity and time preserving boundary conditions. We are interested in the interplay between the geometry and spectrum. After introducing a suitable Hilbert space framework in the general situation, which enables us to realize the Laplace-Beltrami operator as an m-sectorial operator, we focus on solvable models defined on manifolds of constant curvature. In some situations, notably for non-Hermitian Robin-type boundary conditions, we are able to prove either the reality of the spectrum or the existence of complex conjugate pairs of eigenvalues, and establish similarity of the non-Hermitian m-sectorial operators to normal or self-adjoint operators. The study is illustrated by numerical computations.Comment: 37 pages, PDFLaTeX with 11 figure

Improved approximation rates for a parabolic control problem with an objective promoting directional sparsity

We discretize a directionally sparse parabolic control problem governed by a linear equation by means of control approximations that are piecewise constant in time and continuous piecewise linear in space. By discretizing the objective functional with the help of appropriate numerical quadrature formulas, we are able to show that the discrete optimal solution exhibits a directional sparse pattern alike the one enjoyed by the continuous solution. Error estimates are obtained and a comparison with the cases of having piecewise approximations of the control or a semilinear state equation are discussed. Numerical experiments that illustrate the theoretical results are included.The first two authors were partially supported by the Spanish Ministerio de Economía y Competitividad under projects MTM2014-57531-P and MTM2017-83185-P

Geometry-controlled kinetics

It has long been appreciated that transport properties can control reaction kinetics. This effect can be characterized by the time it takes a diffusing molecule to reach a target -- the first-passage time (FPT). Although essential to quantify the kinetics of reactions on all time scales, determining the FPT distribution was deemed so far intractable. Here, we calculate analytically this FPT distribution and show that transport processes as various as regular diffusion, anomalous diffusion, diffusion in disordered media and in fractals fall into the same universality classes. Beyond this theoretical aspect, this result changes the views on standard reaction kinetics. More precisely, we argue that geometry can become a key parameter so far ignored in this context, and introduce the concept of "geometry-controlled kinetics". These findings could help understand the crucial role of spatial organization of genes in transcription kinetics, and more generally the impact of geometry on diffusion-limited reactions.Comment: Submitted versio

Sparse initial data indentification for parabolic pde and its finite element approximations

We address the problem of inverse source identification for parabolic equations from the optimal control viewpoint employing measures of minimal norm as initial data. We adopt the point of view of approximate controllability so that the target is not required to be achieved exactly but only in an approximate sense. We prove an approximate inversion result and derive a characterization of the optimal initial measures by means of duality and the minimization of a suitable quadratic functional on the solutions of the adjoint system. We prove the sparsity of the optimal initial measures showing that they are supported in sets of null Lebesgue measure. As a consequence, approximate controllability can be achieved efficiently by means of controls that are activated in a finite number of pointwise locations. Moreover, we discuss the finite element numerical approximation of the control problem providing a convergence result of the corresponding optimal measures and states as the discretization parameters tend to zero.The first author was supported by Spanish Ministerio de Economía y Competitividad under project MTM2011-22711. The third author was supported by the Advanced Grant NUMERIWAVES/FP7-246775 of the European Research Council Executive Agency, FA9550-14-1-0214 of the EOARD-AFOSR, FA9550-15-1-0027 of AFOSR, the BERC 2014-2017 program of the Basque Government, the MTM2011-29306 and SEV-2013-0323 Grants of the MINECO, the CIMI-Toulouse Excellence Chair in PDEs, Control and Numerics and a Humboldt Award at the University of Erlangen-Nürnberg

Protein Diffusion in Mammalian Cell Cytoplasm

We introduce a new method for mesoscopic modeling of protein diffusion in an entire cell. This method is based on the construction of a three-dimensional digital model cell from confocal microscopy data. The model cell is segmented into the cytoplasm, nucleus, plasma membrane, and nuclear envelope, in which environment protein motion is modeled by fully numerical mesoscopic methods. Finer cellular structures that cannot be resolved with the imaging technique, which significantly affect protein motion, are accounted for in this method by assigning an effective, position-dependent porosity to the cell. This porosity can also be determined by confocal microscopy using the equilibrium distribution of a non-binding fluorescent protein. Distinction can now be made within this method between diffusion in the liquid phase of the cell (cytosol/nucleosol) and the cytoplasm/nucleoplasm. Here we applied the method to analyze fluorescence recovery after photobleach (FRAP) experiments in which the diffusion coefficient of a freely-diffusing model protein was determined for two different cell lines, and to explain the clear difference typically observed between conventional FRAP results and those of fluorescence correlation spectroscopy (FCS). A large difference was found in the FRAP experiments between diffusion in the cytoplasm/nucleoplasm and in the cytosol/nucleosol, for all of which the diffusion coefficients were determined. The cytosol results were found to be in very good agreement with those by FCS