Cell migration on material-driven fibronectin microenvironments

Cell migration is a fundamental process involved in a wide range of biological phenomena. However, how the underlying mechanisms that control migration are orchestrated is not fully understood. In this work, we explore the migratory characteristics of human fibroblasts using different organisations of fibronectin (FN) triggered by two chemically similar surfaces, poly(ethyl acrylate) (PEA) and poly(methyl acrylate) (PMA); cell migration is mediated via an intermediate layer of fibronectin (FN). FN is organised into nanonetworks upon simple adsorption on PEA whereas a globular conformation is observed on PMA. We studied cell speed over the course of 24 h and the morphology of focal adhesions in terms of area and length. Additionally, we analysed the amount of cell-secreted FN as well as FN remodelling. Velocity of human fibroblasts was found to exhibit a biphasic behaviour on PEA, whereas it remained fairly constant on PMA. FA analysis revealed more mature focal adhesions on PEA over time contrary to smaller FAs found on PMA. Finally, human fibroblasts seemed to remodel adsorbed FN more on PMA than on PEA. Overall, these results indicate that the cell–protein–material interface affects cell migratory behaviour. Analysis of FAs together with FN secretion and remodelling were associated with differences in cell velocity providing insights into the factors that can modulate cell motility

Semiclassical and quantum Liouville theory

We develop a functional integral approach to quantum Liouville field theory completely independent of the hamiltonian approach. To this end on the sphere topology we solve the Riemann-Hilbert problem for three singularities of finite strength and a fourth one infinitesimal, by determining perturbatively the Poincare' accessory parameters. This provides the semiclassical four point vertex function with three finite charges and a fourth infinitesimal. Some of the results are extended to the case of n finite charges and m infinitesimal. With the same technique we compute the exact Green function on the sphere on the background of three finite singularities. Turning to the full quantum problem we address the calculation of the quantum determinant on the background of three finite charges and of the further perturbative corrections. The zeta function regularization provides a theory which is not invariant under local conformal transformations. Instead by employing a regularization suggested in the case of the pseudosphere by Zamolodchikov and Zamolodchikov we obtain the correct quantum conformal dimensions from the one loop calculation and we show explicitly that the two loop corrections do not change such dimensions. We then apply the method to the case of the pseudosphere with one finite singularity and compute the exact value for the quantum determinant. Such results are compared to those of the conformal bootstrap approach finding complete agreement.Comment: 12 pages, 1 figure, Contributed to 5th Meeting on Constrained Dynamics and Quantum Gravity (QG05), Cala Gonone, Sardinia, Italy, 12-16 Sep 200

Duration of remission after halving of the etanercept dose in patients with ankylosing spondylitis: a randomized, prospective, long-term, follow-up study

Fabrizio Cantini, Laura Niccoli, Emanuele Cassarà, Olga Kaloudi, Carlotta NanniniDivision of Rheumatology, Misericordia e Dolce Hospital, Prato, ItalyBackground: The aim of this study was to evaluate the proportion of patients with ankylosing spondylitis maintaining clinical remission after reduction of their subcutaneous etanercept dose to 50 mg every other week compared with that in patients receiving etanercept 50 mg weekly.Methods: In the first phase of this randomized, prospective, follow-up study, all biologic-naïve patients identified between January 2005 and December 2009 as satisfying the modified New York clinical criteria for ankylosing spondylitis treated with etanercept 50 mg weekly were evaluated for disease remission in January 2010. In the second phase, patients meeting the criteria for remission were randomized to receive subcutaneous etanercept as either 50 mg weekly or 50 mg every other week. The randomization allocation was 1:1. Remission was defined as Bath Ankylosing Spondylitis Disease Activity Index < 4, no extra-axial manifestations of peripheral arthritis, dactylitis, tenosynovitis, or iridocyclitis, and normal acute-phase reactants. The patients were assessed at baseline, at weeks 4 and 12, and every 12 weeks thereafter. The last visit constituted the end of the follow-up.Results: During the first phase, 78 patients with ankylosing spondylitis (57 males and 21 females, median age 38 years, median disease duration 12 years) were recruited. In January 2010, after a mean follow-up of 25 ± 11 months, 43 (55.1%) patients achieving clinical remission were randomized to one of the two treatment arms. Twenty-two patients received etanercept 50 mg every other week (group 1) and 21 received etanercept 50 mg weekly (group 2). At the end of follow-up, 19 of 22 (86.3%) subjects in group 1 and 19 of 21 (90.4%) in group 2 were still in remission, with no significant difference between the two groups. The mean follow-up duration in group 1 and group 2 was 22 ± 1 months and 21 ± 1.6 months, respectively.Conclusion: Remission of ankylosing spondylitis is possible in at least 50% of patients treated with etanercept 50 mg weekly. After halving of the etanercept dose, remission is maintained in a high percentage of patients during long-term follow-up, with important economic implications.Keywords: ankylosing spondylitis, anti-tumor necrosis factor, etanercept, remission, dose reductio

Polygon model from first order gravity

The gauge fixed polygon model of 2+1 gravity with zero cosmological constant and arbitrary number of spinless point particles is reconstructed from the first order formalism of the theory in terms of the triad and the spin connection. The induced symplectic structure is calculated and shown to agree with the canonical one in terms of the variables.Comment: 20 pages, presentation improved, typos correcte

Loop Quantum Gravity a la Aharonov-Bohm

The state space of Loop Quantum Gravity admits a decomposition into orthogonal subspaces associated to diffeomorphism equivalence classes of spin-network graphs. In this paper I investigate the possibility of obtaining this state space from the quantization of a topological field theory with many degrees of freedom. The starting point is a 3-manifold with a network of defect-lines. A locally-flat connection on this manifold can have non-trivial holonomy around non-contractible loops. This is in fact the mathematical origin of the Aharonov-Bohm effect. I quantize this theory using standard field theoretical methods. The functional integral defining the scalar product is shown to reduce to a finite dimensional integral over moduli space. A non-trivial measure given by the Faddeev-Popov determinant is derived. I argue that the scalar product obtained coincides with the one used in Loop Quantum Gravity. I provide an explicit derivation in the case of a single defect-line, corresponding to a single loop in Loop Quantum Gravity. Moreover, I discuss the relation with spin-networks as used in the context of spin foam models.Comment: 19 pages, 1 figure; v2: corrected typos, section 4 expanded

Some Exact Results for the Exclusion Process

The asymmetric simple exclusion process (ASEP) is a paradigm for non-equilibrium physics that appears as a building block to model various low-dimensional transport phenomena, ranging from intracellular traffic to quantum dots. We review some recent results obtained for the system on a periodic ring by using the Bethe Ansatz. We show that this method allows to derive analytically many properties of the dynamics of the model such as the spectral gap and the generating function of the current. We also discuss the solution of a generalized exclusion process with $N$-species of particles and explain how a geometric construction inspired from queuing theory sheds light on the Matrix Product Representation technique that has been very fruitful to derive exact results for the ASEP.Comment: 21 pages; Proceedings of STATPHYS24 (Cairns, Australia, July 2010

Loop model with mixed boundary conditions, qKZ equation and alternating sign matrices

The integrable loop model with mixed boundary conditions based on the 1-boundary extended Temperley--Lieb algebra with loop weight 1 is considered. The corresponding qKZ equation is introduced and its minimal degree solution described. As a result, the sum of the properly normalized components of the ground state in size L is computed and shown to be equal to the number of Horizontally and Vertically Symmetric Alternating Sign Matrices of size 2L+3. A refined counting is also considered

Spin chains with dynamical lattice supersymmetry

Spin chains with exact supersymmetry on finite one-dimensional lattices are considered. The supercharges are nilpotent operators on the lattice of dynamical nature: they change the number of sites. A local criterion for the nilpotency on periodic lattices is formulated. Any of its solutions leads to a supersymmetric spin chain. It is shown that a class of special solutions at arbitrary spin gives the lattice equivalents of the N=(2,2) superconformal minimal models. The case of spin one is investigated in detail: in particular, it is shown that the Fateev-Zamolodchikov chain and its off-critical extension admits a lattice supersymmetry for all its coupling constants. Its supersymmetry singlets are thoroughly analysed, and a relation between their components and the weighted enumeration of alternating sign matrices is conjectured.Comment: Revised version, 52 pages, 2 figure

Classical conformal blocks from TBA for the elliptic Calogero-Moser system

The so-called Poghossian identities connecting the toric and spherical blocks, the AGT relation on the torus and the Nekrasov-Shatashvili formula for the elliptic Calogero-Moser Yang's (eCMY) functional are used to derive certain expressions for the classical 4-point block on the sphere. The main motivation for this line of research is the longstanding open problem of uniformization of the 4-punctured Riemann sphere, where the 4-point classical block plays a crucial role. It is found that the obtained representation for certain 4-point classical blocks implies the relation between the accessory parameter of the Fuchsian uniformization of the 4-punctured sphere and the eCMY functional. Additionally, a relation between the 4-point classical block and the $N_f=4$, ${\sf SU(2)}$ twisted superpotential is found and further used to re-derive the instanton sector of the Seiberg-Witten prepotential of the $N_f=4$, ${\sf SU(2)}$ supersymmetric gauge theory from the classical block.Comment: 25 pages, no figures, latex+JHEP3, published versio

Identification of a novel zinc metalloprotease through a global analysis of clostridium difficile extracellular proteins

Clostridium difficile is a major cause of infectious diarrhea worldwide. Although the cell surface proteins are recognized to be important in clostridial pathogenesis, biological functions of only a few are known. Also, apart from the toxins, proteins exported by C. difficile into the extracellular milieu have been poorly studied. In order to identify novel extracellular factors of C. difficile, we analyzed bacterial culture supernatants prepared from clinical isolates, 630 and R20291, using liquid chromatography-tandem mass spectrometry. The majority of the proteins identified were non-canonical extracellular proteins. These could be largely classified into proteins associated to the cell wall (including CWPs and extracellular hydrolases), transporters and flagellar proteins. Seven unknown hypothetical proteins were also identified. One of these proteins, CD630_28300, shared sequence similarity with the anthrax lethal factor, a known zinc metallopeptidase. We demonstrated that CD630_28300 (named Zmp1) binds zinc and is able to cleave fibronectin and fibrinogen in vitro in a zinc-dependent manner. Using site-directed mutagenesis, we identified residues important in zinc binding and enzymatic activity. Furthermore, we demonstrated that Zmp1 destabilizes the fibronectin network produced by human fibroblasts. Thus, by analyzing the exoproteome of C. difficile, we identified a novel extracellular metalloprotease that may be important in key steps of clostridial pathogenesis