TrkA+ Neurons Induce Pathologic Regeneration After Soft Tissue Trauma

Heterotopic ossification (HO) is a dynamic, complex pathologic process that often occurs after severe polytrauma trauma, resulting in an abnormal mesenchymal stem cell differentiation leading to ectopic bone growth in soft-tissues including tendons, ligaments, and muscles. The abnormal bone structure and location induce pain and loss of mobility. Recently, we observed that NGF (Nerve growth factor)-responsive TrkA (Tropomyosin receptor kinase A)-expressing nerves invade sites of soft-tissue trauma, and this is a necessary feature for heterotopic bone formation at sites of injury. Here, we assayed the effects of the partial TrkA agonist Gambogic amide (GA) in peritendinous heterotopic bone after extremity trauma. Mice underwent HO induction using the burn/tenotomy model with or without systemic treatment with GA, followed by an examination of the injury site via radiographic imaging, histology, and immunohistochemistry. Single-cell RNA Sequencing confirmed an increase in neurotrophin signaling activity after HO-inducing extremity trauma. Next, TrkA agonism led to injury site hyper-innervation, more brisk expression of cartilage antigens within the injured tendon, and a shift from FGF to TGF beta signaling activity among injury site cells. Nine weeks after injury, this culminated in higher overall levels of heterotopic bone among GA-treated animals. In summary, these studies further link injury site hyper-innervation with increased vascular ingrowth and ultimately heterotopic bone after trauma. In the future, modulation of TrkA signaling may represent a potent means to prevent the trauma-induced heterotopic bone formation and improve tissue regeneration

Reverse Bisimulations on Stable Configuration Structures

The relationships between various equivalences on configuration structures, including interleaving bisimulation (IB), step bisimulation (SB) and hereditary history-preserving (HH) bisimulation, have been investigated by van Glabbeek and Goltz (and later Fecher). Since HH bisimulation may be characterised by the use of reverse as well as forward transitions, it is of interest to investigate forms of IB and SB where both forward and reverse transitions are allowed. We give various characterisations of reverse SB, showing that forward steps do not add extra power. We strengthen Bednarczyk's result that, in the absence of auto-concurrency, reverse IB is as strong as HH bisimulation, by showing that we need only exclude auto-concurrent events at the same depth in the configuration

A Logic with Reverse Modalities for History-preserving Bisimulations

We introduce event identifier logic (EIL) which extends Hennessy-Milner logic by the addition of (1) reverse as well as forward modalities, and (2) identifiers to keep track of events. We show that this logic corresponds to hereditary history-preserving (HH) bisimulation equivalence within a particular true-concurrency model, namely stable configuration structures. We furthermore show how natural sublogics of EIL correspond to coarser equivalences. In particular we provide logical characterisations of weak history-preserving (WH) and history-preserving (H) bisimulation. Logics corresponding to HH and H bisimulation have been given previously, but not to WH bisimulation (when autoconcurrency is allowed), as far as we are aware. We also present characteristic formulas which characterise individual structures with respect to history-preserving equivalences.Comment: In Proceedings EXPRESS 2011, arXiv:1108.407

Systemic DKK1 neutralization enhances human adipose-derived stem cell mediated bone repair

: Progenitor cells from adipose tissue are able to induce bone repair; however, inconsistent or unreliable efficacy has been reported across preclinical and clinical studies. Soluble inhibitory factors, such as the secreted Wnt signaling antagonists Dickkopf-1 (DKK1), are expressed to variable degrees in human adipose-derived stem cells (ASCs), and may represent a targetable "molecular brake" on ASC mediated bone repair. Here, anti-DKK1 neutralizing antibodies were observed to increase the osteogenic differentiation of human ASCs in vitro, accompanied by increased canonical Wnt signaling. Human ASCs were next engrafted into a femoral segmental bone defect in NOD-Scid mice, with animals subsequently treated with systemic anti-DKK1 or isotype control during the repair process. Human ASCs alone induced significant but modest bone repair. However, systemic anti-DKK1 induced an increase in human ASC engraftment and survival, an increase in vascular ingrowth, and ultimately improved bone repair outcomes. In summary, anti-DKK1 can be used as a method to augment cell-mediated bone regeneration, and could be particularly valuable in the contexts of impaired bone healing such as osteoporotic bone repair

Dynamic Temperature Measurement for Magnetocaloric Materials

International audienceA device to measure the dynamic response of magnetocaloric effect in terms of temperature change at different speed and up to 1 T/ms has been developed. The magnetic source is based on rotating magnets and the temperature measurement on thermocouple. This prototype will be able to explore the dynamic response of magnetocaloric effect under controlled temperature for different type of material: first order and second order phase transition material

Dynamic Temperature Measurement for Magnetocaloric Materials

International audienceA device to measure the dynamic response of magnetocaloric effect in terms of temperature change at different speed and up to 1 T/ms has been developed. The magnetic source is based on rotating magnets and the temperature measurement on thermocouple. This prototype will be able to explore the dynamic response of magnetocaloric effect under controlled temperature for different type of material: first order and second order phase transition material

On PAC-Bayesian reconstruction guarantees for VAEs

Despite its wide use and empirical successes, the theoretical understanding and study of the behaviour and performance of the variational autoencoder (VAE) have only emerged in the past few years. We contribute to this recent line of work by analysing the VAE’s reconstruction ability for unseen test data, leveraging arguments from the PAC-Bayes theory. We provide generalisation bounds on the theoretical reconstruction error, and provide insights on the regularisation effect of VAE objectives. We illustrate our theoretical results with supporting experiments on classical benchmark datasets

Implications of the calf musculature and Achilles tendon architectures for understanding the site of injury

Clinically the sites of Achilles Tendon (AT) overuse conditions can be divided into the tendon mid-portion and osteotendinous attachment. Purpose: We propose an anatomical analysis of the triceps surae musculotendon unit that could provide a possible anatomic explanation for these 2 sites of injury. Method: Twelve cadavers (age 74±7 years) were studied. In both legs, calf muscles (lateral gastrocnemius (LG), medial gastrocnemius (MG) and soleus) were dissected and their volumes measured. Fine saw cuts were made in the sagittal plane, either side of the midline of the calcaneus. Each strip contained the distal part of the tendon and its insertion, together with the superior tuberosity of the calcaneus. Trabecular architecture was analyzed from X-rays taken with Faxitron radiography. Histological sections of the enthesis and the thickness of the uncalcified fibrocartilage and the subchondral plate were evaluated. A finite element model of tendon coupled to a rupture index was developed to investigate the AT response to mechanical load. Results: Muscle volume was highest for the soleus, followed by the MG, and LG. Within the AT, the soleus fibers occupy the antero-medial parts, the MG fibers form the posterior lateral layer, yet the LG head fibers retain the antero-lateral part. The quantity of bone and the apparent trabecular thickness at the enthesis were greatest in the central part of the enthesis. Thickness of calcified fibrocartilage tissue was significantly greater in the central part than medially (P=0.04) and laterally (P=0.03). Uncalcified fibrocartilage was significantly thicker medially than laterally (P=0.02). Finally, finite element analysis showed that AT mechanical stress increased with muscle load and converged at 4.6–7.9cm of the enthesis. Conclusion: Our data suggest that the triceps surae musculotendon unit is composed of anatomically distinct parts that undergo non-uniform mechanical loading. There are two sites where potentially tendon mechanical stress increases, the medial/central portions of the enthesis and the tendon midportion

Schedulers and finishers : on generating the behaviours of an event structure

It is well known that every trace of a transition system can be generated using a scheduler. However, this basic completeness result does not hold in event structure models. The reason for this failure is that, according to its standard definition, a scheduler chooses which action to schedule and, at the same time, finishes the one scheduled last. Thus, scheduled events will never be able to overlap. We propose to separate scheduling from finishing and introduce the dual notion of finishers which, together with schedulers, are enough to regain completeness back. We then investigate all possible interactions between schedulers and finishers, concluding that simple alternating interactions are enough to express complex ones. Finally, we show how finishers can be used to filter behaviours to the extent to which they capture intrinsic system characteristics.18 page(s