A bioactive hybrid three-dimensional tissue-engineering construct for cartilage repair

The aim was to develop a hybrid three-dimensional-tissue engineering construct for chondrogenesis. The hypothesis was that they support chondrogenesis. A biodegradable, highly porous polycaprolactone-grate was produced by solid freeform fabrication. The polycaprolactone support was coated with a chitosan/polyethylene oxide nanofibre sheet produced by electrospinning. Transforming growth factor-3-induced chondrogenesis was followed using the following markers: sex determining region Y/-box 9, runt-related transcription factor 2 and collagen II and X in quantitative real-time polymerase chain reaction, histology and immunostaining. A polycaprolactone-grate and an optimized chitosan/polyethylene oxide nanofibre sheet supported cellular aggregation, chondrogenesis and matrix formation. In tissue engineering constructs, the sheets were seeded first with mesenchymal stem cells and then piled up according to the lasagne principle. The advantages of such a construct are (1) the cells do not need to migrate to the tissue engineering construct and therefore pore size and interconnectivity problems are omitted and (2) the cell-tight nanofibre sheet and collagen-fibre network mimic a cell culture platform for mesenchymal stem cells/chondrocytes (preventing escape) and hinders in-growth of fibroblasts and fibrous scarring (preventing capture). This allows time for the slowly progressing, multiphase true cartilage regeneration.Peer reviewe

On the top eigenvalue of heavy-tailed random matrices

We study the statistics of the largest eigenvalue lambda_max of N x N random matrices with unit variance, but power-law distributed entries, P(M_{ij})~ |M_{ij}|^{-1-mu}. When mu > 4, lambda_max converges to 2 with Tracy-Widom fluctuations of order N^{-2/3}. When mu < 4, lambda_max is of order N^{2/mu-1/2} and is governed by Fr\'echet statistics. The marginal case mu=4 provides a new class of limiting distribution that we compute explicitely. We extend these results to sample covariance matrices, and show that extreme events may cause the largest eigenvalue to significantly exceed the Marcenko-Pastur edge. Connections with Directed Polymers are briefly discussed.Comment: 4 pages, 2 figure

An exclusion process on a tree with constant aggregate hopping rate

We introduce a model of a totally asymmetric simple exclusion process (TASEP) on a tree network where the aggregate hopping rate is constant from level to level. With this choice for hopping rates the model shows the same phase diagram as the one-dimensional case. The potential applications of our model are in the area of distribution networks; where a single large source supplies material to a large number of small sinks via a hierarchical network. We show that mean field theory (MFT) for our model is identical to that of the one-dimensional TASEP and that this mean field theory is exact for the TASEP on a tree in the limit of large branching ratio, $b$(or equivalently large coordination number). We then present an exact solution for the two level tree (or star network) that allows the computation of any correlation function and confirm how mean field results are recovered as $b\rightarrow\infty$. As an example we compute the steady-state current as a function of branching ratio. We present simulation results that confirm these results and indicate that the convergence to MFT with large branching ratio is quite rapid.Comment: 20 pages. Submitted to J. Phys.

Area distribution and the average shape of a L\'evy bridge

We consider a one dimensional L\'evy bridge x_B of length n and index 0 < \alpha < 2, i.e. a L\'evy random walk constrained to start and end at the origin after n time steps, x_B(0) = x_B(n)=0. We compute the distribution P_B(A,n) of the area A = \sum_{m=1}^n x_B(m) under such a L\'evy bridge and show that, for large n, it has the scaling form P_B(A,n) \sim n^{-1-1/\alpha} F_\alpha(A/n^{1+1/\alpha}), with the asymptotic behavior F_\alpha(Y) \sim Y^{-2(1+\alpha)} for large Y. For \alpha=1, we obtain an explicit expression of F_1(Y) in terms of elementary functions. We also compute the average profile < \tilde x_B (m) > at time m of a L\'evy bridge with fixed area A. For large n and large m and A, one finds the scaling form = n^{1/\alpha} H_\alpha({m}/{n},{A}/{n^{1+1/\alpha}}), where at variance with Brownian bridge, H_\alpha(X,Y) is a non trivial function of the rescaled time m/n and rescaled area Y = A/n^{1+1/\alpha}. Our analytical results are verified by numerical simulations.Comment: 21 pages, 4 Figure

Evidence of Υ(1S)→J/ψ+χc1\Upsilon(1S) \to J/\psi+\chi_{c1} and search for double-charmonium production in Υ(1S)\Upsilon(1S) and Υ(2S)\Upsilon(2S) decays

Using data samples of $102\times10^6$ $\Upsilon(1S)$ and $158\times10^6$ $\Upsilon(2S)$ events collected with the Belle detector, a first experimental search has been made for double-charmonium production in the exclusive decays $\Upsilon(1S,2S)\rightarrow J/\psi(\psi')+X$, where $X=\eta_c$, $\chi_{cJ} (J=~0,~1,~2)$, $\eta_c(2S)$, $X(3940)$, and $X(4160)$. No significant signal is observed in the spectra of the mass recoiling against the reconstructed $J/\psi$ or $\psi'$ except for the evidence of $\chi_{c1}$ production with a significance of $4.6\sigma$ for $\Upsilon(1S)\rightarrow J/\psi+\chi_{c1}$. The measured branching fraction \BR(\Upsilon(1S)\rightarrow J/\psi+\chi_{c1}) is $(3.90\pm1.21(\rm stat.)\pm0.23 (\rm syst.))\times10^{-6}$. The $90\%$ confidence level upper limits on the branching fractions of the other modes having a significance of less than $3\sigma$ are determined. These results are consistent with theoretical calculations using the nonrelativistic QCD factorization approach.Comment: 12 pages, 4 figures, 1 table. The fit range was extended to include X(4160) signal according to referee's suggestions. Other results unchanged. Paper was accepted for publication as a regular article in Physical Review

Impact of Positive Lymph Nodes and Resection Margin Status on the Overall Survival of Patients with Resected Perihilar Cholangiocarcinoma: The ENSCCA Registry

Background: Lymph node metastasis and positive resection margins have been reported to be major determinants of overall survival (OS) and poor recurrence-free survival (RFS) for patients who underwent resection for perihilar cholangiocarcinoma (pCCA). However, the prognostic value of positive lymph nodes independently from resection margin status on OS has not been evaluated. Methods: From the European Cholangiocarcinoma (ENSCCA) registry, patients who underwent resection for pCCA between 1994 and 2021 were included in this retrospective cohort study. The primary outcome was OS stratified for resection margin and lymph node status. The secondary outcome was recurrence-free survival. Results: A total of 325 patients from 11 different centers and six European countries were included. Of these, 194 (59.7%) patients had negative resection margins. In 113 (34.8%) patients, positive lymph nodes were found. Lymph node status, histological grade, and ECOG performance status were independent prognostic factors for survival. The median OS for N0R0, N0R1, N+R0, and N+R1 was 38, 30, 18, and 12 months, respectively (p < 0.001). Conclusion: These data indicate that in the presence of positive regional lymph nodes, resection margin status does not determine OS or RFS in patients with pCCA. Achieving negative margins in patients with positive nodes should not come at the expense of more extensive surgery and associated higher mortality.The ENSCCA Registry is completely funded by the European Association for the Study of the Liver (EASL; Registry grant awards 2016 and 2019 to J.M.B.), Incyte Bioscience International Sàrl (grant award 2020 to J.M.B.) and European Union’s Horizon 2020 Research and Innovation Program (grant number 825510, ESCALON: to J.M.B. and A.L.)

Retinoic Acid Functions as a Key GABAergic Differentiation Signal in the Basal Ganglia

Retinoic acid (RA) is essential for the generation of GABAergic inhibitory neurons in the mouse forebrain, and RA treatment of embryonic stem cells induces the production of GABAergic neurons

A nomenclature for restriction enzymes, DNA methyltransferases, homing endonucleases and their genes

A nomenclature is described for restriction endonucleases, DNA methyltransferases, homing endonucleases and related genes and gene products. It provides explicit categories for the many different Type II enzymes now identified and provides a system for naming the putative genes found by sequence analysis of microbial genome