Mesenchymal stem cells for the treatment of systemic lupus erythematosus: is the cure for connective tissue diseases within connective tissue?

Mesenchymal stem cells (MSCs) are now known to display not only adult stem cell multipotency but also robust anti-inflammatory and regenerative properties. After widespread in vitro and in vivo preclinical testing in several autoimmune disease models, allogenic MSCs have been successfully applied in patients with severe treatment-refractory systemic lupus erythematosus. The impressive results of these uncontrolled phase I and II trials - mostly in patients with non-responding renal disease - point to the need to perform controlled multicentric trials. In addition, they suggest that there is much to be learned from the basic and clinical science of MSCs in order to reap the full potential of these multifaceted progenitor cells in the treatment of autoimmune diseases

Big brother is watching - using digital disease surveillance tools for near real-time forecasting

Abstract for the International Journal of Infectious Diseases 79 (S1) (2019).https://www.ijidonline.com/article/S1201-9712(18)34659-9/abstractPublished versio

Glueball Regge trajectories from gauge/string duality and the Pomeron

The spectrum of light baryons and mesons has been reproduced recently by Brodsky and Teramond from a holographic dual to QCD inspired in the AdS/CFT correspondence. They associate fluctuations about the AdS geometry with four dimensional angular momenta of the dual QCD states. We use a similar approach to estimate masses of glueball states with different spins and their excitations. We consider Dirichlet and Neumann boundary conditions and find approximate linear Regge trajectories for these glueballs. In particular the Neumann case is consistent with the Pomeron trajectory.Comment: In this revised version we made some additional remarks on the text. We also included 2 more references. The glueball spectrum and Regge trajectories are unchanged. 10 pages, 2 eps figure

A Self-Organized Method for Computing the Epidemic Threshold in Computer Networks

In many cases, tainted information in a computer network can spread in a way similar to an epidemics in the human world. On the other had, information processing paths are often redundant, so a single infection occurrence can be easily "reabsorbed". Randomly checking the information with a central server is equivalent to lowering the infection probability but with a certain cost (for instance processing time), so it is important to quickly evaluate the epidemic threshold for each node. We present a method for getting such information without resorting to repeated simulations. As for human epidemics, the local information about the infection level (risk perception) can be an important factor, and we show that our method can be applied to this case, too. Finally, when the process to be monitored is more complex and includes "disruptive interference", one has to use actual simulations, which however can be carried out "in parallel" for many possible infection probabilities

Satellite laser ranging work at the Goddard Space Flight Center

Laser ranging systems, their range and accuracy capabilities, and planned improvements for future systems are discussed, the systems include one fixed and two mobile lasers ranging systems. They have demonstrated better than 10 cm accuracy both on a carefully surveyed ground range and in regular satellite ranging operations. They are capable of ranging to all currently launched retroreflector equipped satellites with the exception of Timation III. A third mobile system is discussed which will be accurate to better than 5 cm and will be capable of ranging to distant satellites such as Timation III and LAGEOS

Mechanical Strength of 17 134 Model Proteins and Cysteine Slipknots

A new theoretical survey of proteins' resistance to constant speed stretching is performed for a set of 17 134 proteins as described by a structure-based model. The proteins selected have no gaps in their structure determination and consist of no more than 250 amino acids. Our previous studies have dealt with 7510 proteins of no more than 150 amino acids. The proteins are ranked according to the strength of the resistance. Most of the predicted top-strength proteins have not yet been studied experimentally. Architectures and folds which are likely to yield large forces are identified. New types of potent force clamps are discovered. They involve disulphide bridges and, in particular, cysteine slipknots. An effective energy parameter of the model is estimated by comparing the theoretical data on characteristic forces to the corresponding experimental values combined with an extrapolation of the theoretical data to the experimental pulling speeds. These studies provide guidance for future experiments on single molecule manipulation and should lead to selection of proteins for applications. A new class of proteins, involving cystein slipknots, is identified as one that is expected to lead to the strongest force clamps known. This class is characterized through molecular dynamics simulations.Comment: 40 pages, 13 PostScript figure

The LRRK2 G2385R variant is a partial loss-of-function mutation that affects synaptic vesicle trafficking through altered protein interactions.

Mutations in the Leucine-rich repeat kinase 2 gene (LRRK2) are associated with familial Parkinson's disease (PD). LRRK2 protein contains several functional domains, including protein-protein interaction domains at its N- and C-termini. In this study, we analyzed the functional features attributed to LRRK2 by its N- and C-terminal domains. We combined TIRF microscopy and synaptopHluorin assay to visualize synaptic vesicle trafficking. We found that N- and C-terminal domains have opposite impact on synaptic vesicle dynamics. Biochemical analysis demonstrated that different proteins are bound at the two extremities, namely \u3b23-Cav2.1 at N-terminus part and \u3b2-Actin and Synapsin I at C-terminus domain. A sequence variant (G2385R) harboured within the C-terminal WD40 domain increases the risk for PD. Complementary biochemical and imaging approaches revealed that the G2385R variant alters strength and quality of LRRK2 interactions and increases fusion of synaptic vesicles. Our data suggest that the G2385R variant behaves like a loss-of-function mutation that mimics activity-driven events. Impaired scaffolding capabilities of mutant LRRK2 resulting in perturbed vesicular trafficking may arise as a common pathophysiological denominator through which different LRRK2 pathological mutations cause diseas

Supersymmetric Rotating Black Holes and Causality Violation

The geodesics of the rotating extreme black hole in five spacetime dimensions found by Breckenridge, Myers, Peet and Vafa are Liouville integrable and may be integrated by additively separating the Hamilton-Jacobi equation. This allows us to obtain the St\"ackel-Killing tensor. We use these facts to give the maximal analytic extension of the spacetime and discuss some aspects of its causal structure. In particular, we exhibit a `repulson'-like behaviour occuring when there are naked closed timelike curves. In this case we find that the spacetime is geodesically complete (with respect to causal geodesics) and free of singularities. When a partial Cauchy surface exists, we show, by solving the Klein-Gordon equation, that the absorption cross-section for massless waves at small frequencies is given by the area of the hole. At high frequencies a dependence on the angular quantum numbers of the wave develops. We comment on some aspects of `inertial time travel' and argue that such time machines cannot be constructed by spinning up a black hole with no naked closed timelike curves.Comment: 36 pages,LaTeX,8 figures;added 1 reference and a few comments; formula (2.6) corrected; a few changes to section