Bone refilling in cortical bone multicellular units: Insights into tetracycline double labelling from a computational model

Bone remodelling is carried out by `bone multicellular units' (BMUs) in which active osteoclasts and active osteoblasts are spatially and temporally coupled. The refilling of new bone by osteoblasts towards the back of the BMU occurs at a rate that depends both on the number of osteoblasts and on their secretory activity. In cortical bone, a linear phenomenological relationship between matrix apposition rate (MAR) and BMU cavity radius is found experimentally. How this relationship emerges from the combination of complex, nonlinear regulations of osteoblast number and secretory activity is unknown. Here, we extend our previous mathematical model of cell development within a single BMU to investigate how osteoblast number and osteoblast secretory activity vary along the BMU's closing cone. MARs predicted by the model are compared with data from tetracycline double labelling experiments. We find that the linear phenomenological relationship observed in these experiments between MAR and BMU cavity radius holds for most of the refilling phase simulated by our model, but not near the start and end of refilling. This suggests that at a particular bone site undergoing remodelling, bone formation starts and ends rapidly. Our model also suggests that part of the observed cross-sectional variability in tetracycline data may be due to different bone sites being refilled by BMUs at different stages of their lifetime. The different stages of a BMU's lifetime depend on whether the cell populations within the BMU are still developing or have reached a quasi-steady state while travelling through bone. We find that due to their longer lifespan, active osteoblasts reach a quasi-steady distribution more slowly than active osteoclasts. We suggest that this fact may locally enlarge the Haversian canal diameter (due to a local lack of osteoblasts compared to osteoclasts) near the BMU's point of origin.Comment: 16 pages, 6 figures, 3 tables. V3: minor changes: added 2 paragraphs (BMU cavity in Section 2 and Model Robustness in Section 4), references [52,54

The pharmacokinetics of penicillamine in a female mongrel dog

The pharmacokinetic parameters of D-penicillamine were investigated by administering four intravenous bolus doses, four oral doses, and six constant rate intravenous infusions to a female mongrel dog at dosages comparable to 250, 500, 750, and 1000 mg in man. The pharmacokinetics of D-penicillamine demonstrated nonlinearity in the dog. There was more than proportional increase in the area under the whole blood concentration curve for an increase in the bolus intravenous dose. The steady state whole blood, plasma, and packed cell levels of penicillamine were increased more than proportionately for an increase in the intravenous infusion rate. Total body clearance of penicillamine was decreased by increasing the dose or the infusion rate of penicillamine. Correspondingly, the estimated half-life of unchanged penicillamine in the whole blood was decreased for increased intravenous bolus doses. The renal clearance of penicillamine was nonlinear, decreasing with time during the bolus experiments and increasing at higher infusion rates. The nonrenal clearance was decreased at higher infusion rates, suggesting that a saturable nonrenal elimination process exists for penicillamine in the dog. The nonlinearities that were observed in the dog, if also present in man, may be responsible in part for the dose related side effects reported clinically for penicillamine .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45080/1/10928_2005_Article_BF01061028.pd

Novel approaches to the Re-assembly, Re-association and Re-unification of cultural heritage collections – the GRAVITATE project solution

The vast majority of archaeological objects are discovered in a fragmentary state, and the poor state of preservation. Moreover, pieces of historical importance and interest may be dispersed across different collections and museums: accidents, wars, natural disasters, human intervention or the ravages of time, often causes the fragmentation of important art pieces and make their reassembly difficult and even impossible due to missing, eroded parts or different ownerships of fragments of a same object. In other cases objects cannot be reached physically, due to various restrictions, such as storage, permanent exhibition or fragility of their preservation state. The paper will introduce an innovative approach to the R3 challenges that these archaeological problems pose: Re-assembly, Re-association, Re-unification of broken artefacts. The novelty relies on the integration of semantic description and similarity search, based on multi-modal indexing of data and information such as 3D geometry, colour, patterns or features, and non-structured texts. The tools described have been developed by a team of researchers within the EU funded project GRAVITATE. The structure and functionality of the GRAVITATE platform will be showcased through the presentation of real archaeological material, such as the 6th century B.C. Salamis (Cyprus) collection of fragmented terracotta statues, unearthed in Cyprus more than a century ago and since then divided among Cyprus and major UK museums

SHREC'18 track: Recognition of geometric patterns over 3D models

International audienceThis track of the SHREC 2018 originally aimed at recognizing relief patterns over a set of triangle meshes from laser scan acquisitions of archaeological fragments. This track approaches a lively and very challenging problem that remains open after the end of the track. In this report we discuss the challenges to face to successfully address geometric pattern recognition over surfaces; how the existing techniques can go further in this direction, what is currently missing and what is necessary to be further developed