Platelet lysate-loaded photocrosslinkable hyaluronic acid hydrogels for periodontal endogenous regenerative technology

The integrity and function of the periodontium can be compromised by traumatic injuries or periodontitis. Currently available clinical therapies are able to stop the progression of periodontitis and allow the healing of periodontal tissue. However an optimal strategy capable of restoring the anatomy and functionality of the lost periodontal tissue is still to be achieved. Herein is proposed the development of an injectable hydrogel system able to release a growth factors and cells to the periodontal defect. This injectable system is based on a photocrosslinkable hydrogel, prepared from methacrylated Hyaluronic Acid (me-HA) and incorporating Platelet Lysate (PL). The delivery of growth factors and cells in situ is expected to enhance regeneration of the periodontium. Various formulations of me-HA containing increasing PL concentrations were studied for achieving the formation of stable photocrosslinkable hydrogels. The produced hydrogels were subsequently characterized to assess mechanical properties, degradation, protein/growth factor release profile, antimicrobial activity and response towards human Periodontal Ligament fibroblasts (hPDLFs). The results demonstrated that it was possible to obtain stable photocrosslinkable hydrogels incorporating different amounts of PL that can be released in a sustained manner. Furthermore, the incorporation of PL improved (p<0.02) the viscoelastic properties of the hydrogels and enhanced their resilience to the degradation by hyaluronidase (HAase). Additionally, the PL showed to provide antimicrobial properties. Finally, hPDLFs, either seeded or encapsulated into the developed hydrogels, showed enhanced proliferation over time (p<0.05), proportionally to the increasing amounts of PL present in the hydrogel formulations

On the Classification of Brane Tilings

We present a computationally efficient algorithm that can be used to generate all possible brane tilings. Brane tilings represent the largest class of superconformal theories with known AdS duals in 3+1 and also 2+1 dimensions and have proved useful for describing the physics of both D3 branes and also M2 branes probing Calabi-Yau singularities. This algorithm has been implemented and is used to generate all possible brane tilings with at most 6 superpotential terms, including consistent and inconsistent brane tilings. The collection of inconsistent tilings found in this work form the most comprehensive study of such objects to date.Comment: 33 pages, 12 figures, 15 table

Remarks on quiver gauge theories from open topological string theory

We study effective quiver gauge theories arising from a stack of D3-branes on certain Calabi-Yau singularities. Our point of view is a first principle approach via open topological string theory. This means that we construct the natural A-infinity-structure of open string amplitudes in the associated D-brane category. Then we show that it precisely reproduces the results of the method of brane tilings, without having to resort to any effective field theory computations. In particular, we prove a general and simple formula for effective superpotentials

D-branes Wrapped on Fuzzy del Pezzo Surfaces

We construct classical solutions in quiver gauge theories on D0-branes probing toric del Pezzo singularities in Calabi-Yau manifolds. Our solutions represent D4-branes wrapped around fuzzy del Pezzo surfaces. We study the fluctuation spectrum around the fuzzy CP^2 solution in detail. We also comment on possible applications of our fuzzy del Pezzo surfaces to the fuzzy version of F-theory, dubbed F(uzz) theory.Comment: 1+42 pages, 9 figures v2: references added v3: statements on the structure of the Yukawa couplings weakened. published versio

Seiberg duality for Chern-Simons quivers and D-brane mutations

Chern-Simons quivers for M2-branes at Calabi-Yau singularities are best understood as the low energy theory of D2-branes on a dual type IIA background. We show how the D2-brane point of view naturally leads to three dimensional Seiberg dualities for Chern-Simons quivers with chiral matter content: They arise from a change of brane basis (or mutation), in complete analogy with the better known Seiberg dualities for D3-brane quivers. This perspective reproduces the known rules for Seiberg dualities in Chern-Simons-Yang-Mills theories with unitary gauge groups. We provide explicit examples of dual theories for the quiver dual to the Y^{p,q}(CP^2) geometries. We also comment on the string theory derivation of CS quivers dual to massive type IIA geometries.Comment: 32 pages+appendix; v2: added a referenc

Wall Crossing, Quivers and Crystals

We study the spectrum of BPS D-branes on a Calabi-Yau manifold using the 0+1 dimensional quiver gauge theory that describes the dynamics of the branes at low energies. The results of Kontsevich and Soibelman predict how the degeneracies change. We argue that Seiberg dualities of the quiver gauge theories, which change the basis of BPS states, correspond to crossing the "walls of the second kind." There is a large class of examples, including local del Pezzo surfaces, where the BPS degeneracies of quivers corresponding to one D6 brane bound to arbitrary numbers of D4, D2 and D0 branes are counted by melting crystal configurations. We show that the melting crystals that arise are a discretization of the Calabi-Yau geometry. The shape of the crystal is determined by the Calabi-Yau geometry and the background B-field, and its microscopic structure by the quiver Q. We prove that the BPS degeneracies computed from Q and Q' are related by the Kontsevich Soibelman formula, using a geometric realization of the Seiberg duality in the crystal. We also show that, in the limit of infinite B-field, the combinatorics of crystals arising from the quivers becomes that of the topological vertex. We thus re-derive the Gromov-Witten/Donaldson-Thomas correspondence

Poloxomer 188 Has a Deleterious Effect on Dystrophic Skeletal Muscle Function

Duchenne muscular dystrophy (DMD) is an X-linked, fatal muscle wasting disease for which there is currently no cure and limited palliative treatments. Poloxomer 188 (P188) is a tri-block copolymer that has been proposed as a potential treatment for cardiomyopathy in DMD patients. Despite the reported beneficial effects of P188 on dystrophic cardiac muscle function, the effects of P188 on dystrophic skeletal muscle function are relatively unknown. Mdx mice were injected intraperitoneally with 460 mg/kg or 30 mg/kg P188 dissolved in saline, or saline alone (control). The effect of single-dose and 2-week daily treatment was assessed using a muscle function test on the Tibialis Anterior (TA) muscle in situ in anaesthetised mice. The test comprises a warm up, measurement of the force-frequency relationship and a series of eccentric contractions with a 10% stretch that have previously been shown to cause a drop in maximum force in mdx mice. After 2 weeks of P188 treatment at either 30 or 460 mg/kg/day the drop in maximum force produced following eccentric contractions was significantly greater than that seen in saline treated control mice (P = 0.0001). Two week P188 treatment at either dose did not significantly change the force-frequency relationship or maximum isometric specific force produced by the TA muscle. In conclusion P188 treatment increases susceptibility to contraction-induced injury following eccentric contractions in dystrophic skeletal muscle and hence its suitability as a potential therapeutic for DMD should be reconsidered

Dynamic SU(2) Structure from Seven-branes

We obtain a family of supersymmetric solutions of type IIB supergravity with dynamic SU(2) structure, which describe the local geometry near a stack of four D7-branes and one O7-plane wrapping a rigid four-cycle. The deformation to a generalized complex geometry is interpreted as a consequence of nonperturbative effects in the seven-brane gauge theory. We formulate the problem for seven-branes wrapping the base of an appropriate del Pezzo cone, and in the near-stack limit in which the four-cycle is flat, we obtain an exact solution in closed form. Our solutions serve to characterize the local geometry of nonperturbatively-stabilized flux compactifications.Comment: 49 pages, 2 figures; v2: minor corrections, references adde

Acral post-traumatic tumoral calcinosis in pregnancy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Tumoral calcinosis is an uncommon disorder characterized by the development of calcified masses within the peri-articular soft tissues of large joints, but rarely occurs within the hand.</p> <p>Case presentation</p> <p>We present the case of a 31-year-old pregnant Indian woman with a three-month history of painful swelling within the tip of her right middle finger following a superficial laceration. She was otherwise well and had normal serum calcium and phosphate levels. Plain radiography demonstrated a dense, lobulated cluster of calcified nodules within the soft tissues of the volar pulp space, consistent with a diagnosis of tumoral calcinosis. This diagnosis was confirmed on the basis of the histopathological examination following surgical excision.</p> <p>Conclusion</p> <p>To the best of our knowledge, we present the only reported case of acral tumoral calcinosis within the finger, and the first description of its occurrence during pregnancy. We review the etiology, pathogenesis and treatment of tumoral calcinosis.</p

The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation.

In the European Union, medicines are authorised for some rare disease only if they are judged to be dissimilar to authorised orphan drugs for that disease. This paper describes the use of 2D fingerprints to show the extent of the relationship between computed levels of structural similarity for pairs of molecules and expert judgments of the similarities of those pairs. The resulting relationship can be used to provide input to the assessment of new active compounds for which orphan drug authorisation is being sought