A Tenon's capsule/bulbar conjunctiva interface biomimetic to model fibrosis and local drug delivery

Glaucoma filtration surgery is one of the most effective methods for lowering intraocular pressure in glaucoma. The surgery efficiently reduces intra-ocular pressure but the most common cause of failure is scarring at the incision site. This occurs in the conjunctiva/Tenon's capsule layer overlying the scleral coat of the eye. Currently used antimetabolite treatments to prevent post-surgical scarring are non-selective and are associated with potentially blinding side effects. Developing new treatments to target scarring requires both a better understanding of wound healing and scarring in the conjunctiva, and new means of delivering anti-scarring drugs locally and sustainably. By combining plastic compression of collagen gels with a soft collagen-based layer, we have developed a physiologically relevant model of the sub-epithelial bulbar conjunctiva/Tenon's capsule interface, which allows a more holistic approach to the understanding of subconjunctival tissue behaviour and local drug delivery. The biomimetic tissue hosts both primary human conjunctival fibroblasts and an immune component in the form of macrophages, morphologically and structurally mimicking the mechanical proprieties and contraction kinetics of ex vivo porcine conjunctiva. We show that our model is suitable for the screening of drugs targeting scarring and/or inflammation, and amenable to the study of local drug delivery devices that can be inserted in between the two layers of the biomimetic. We propose that this multicellular-bilayer engineered tissue will be useful to study complex biological aspects of scarring and fibrosis, including the role of inflammation, with potentially significant implications for the management of scarring following glaucoma filtration surgery and other anterior ocular segment scarring conditions. Crucially, it uniquely allows the evaluation of new means of local drug delivery within a physiologically relevant tissue mimetic, mimicking intraoperative drug delivery in vivo

Three-dimensional description of the Φ1,3\Phi_{1,3} deformation of minimal models

We discuss the $2+1$ dimensional description of the $\Phi_{1,3}$ deformation of the minimal model $M_p$ leading to a transition $M_p \rightarrow M_{p-1}$. The deformation can be considered as an addition of the charged matter to the Chern-Simons theory describing a minimal model. The $N=1$ superconformal case is also considered.Comment: 12 pages, plain Late

The Many Faces of a Character

We prove an identity between three infinite families of polynomials which are defined in terms of `bosonic', `fermionic', and `one-dimensional configuration' sums. In the limit where the polynomials become infinite series, they give different-looking expressions for the characters of the two integrable representations of the affine $su(2)$ algebra at level one. We conjecture yet another fermionic sum representation for the polynomials which is constructed directly from the Bethe-Ansatz solution of the Heisenberg spin chain.Comment: 14/9 pages in harvmac, Tel-Aviv preprint TAUP 2125-9

Fermionic representations for characters of M(3,t), M(4,5), M(5,6) and M(6,7) minimal models and related Rogers-Ramanujan type and dilogarithm identities

Characters and linear combinations of characters that admit a fermionic sum representation as well as a factorized form are considered for some minimal Virasoro models. As a consequence, various Rogers-Ramanujan type identities are obtained. Dilogarithm identities producing corresponding effective central charges and secondary effective central charges are derived. Several ways of constructing more general fermionic representations are discussed.Comment: 14 pages, LaTex; minor correction

Irreducible Characters of General Linear Superalgebra and Super Duality

We develop a new method to solve the irreducible character problem for a wide class of modules over the general linear superalgebra, including all the finite-dimensional modules, by directly relating the problem to the classical Kazhdan-Lusztig theory. We further verify a parabolic version of a conjecture of Brundan on the irreducible characters in the BGG category \mc{O} of the general linear superalgebra. We also prove the super duality conjecture

Urinary secretion and extracellular aggregation of mutant uromodulin isoforms

Uromodulin is exclusively expressed in the thick ascending limb and is the most abundant protein secreted in urine where it is found in high-molecular-weight polymers. Its biological functions are still elusive, but it is thought to play a protective role against urinary tract infection, calcium oxalate crystal formation, and regulation of water and salt balance in the thick ascending limb. Mutations in uromodulin are responsible for autosomal-dominant kidney diseases characterized by defective urine concentrating ability, hyperuricemia, gout, tubulointerstitial fibrosis, renal cysts, and chronic kidney disease. Previous in vitro studies found retention in the endoplasmic reticulum as a common feature of all uromodulin mutant isoforms. Both in vitro and in vivo we found that mutant isoforms partially escaped retention in the endoplasmic reticulum and reached the plasma membrane where they formed large extracellular aggregates that have a dominant-negative effect on coexpressed wild-type protein. Notably, mutant uromodulin excretion was detected in patients carrying uromodulin mutations. Thus, our results suggest that mutant uromodulin exerts a gain-of-function effect that can be exerted by both intra- and extracellular forms of the protein

The spin-1/2 XXZ Heisenberg chain, the quantum algebra U_q[sl(2)], and duality transformations for minimal models

The finite-size scaling spectra of the spin-1/2 XXZ Heisenberg chain with toroidal boundary conditions and an even number of sites provide a projection mechanism yielding the spectra of models with a central charge c<1 including the unitary and non-unitary minimal series. Taking into account the half-integer angular momentum sectors - which correspond to chains with an odd number of sites - in many cases leads to new spinor operators appearing in the projected systems. These new sectors in the XXZ chain correspond to a new type of frustration lines in the projected minimal models. The corresponding new boundary conditions in the Hamiltonian limit are investigated for the Ising model and the 3-state Potts model and are shown to be related to duality transformations which are an additional symmetry at their self-dual critical point. By different ways of projecting systems we find models with the same central charge sharing the same operator content and modular invariant partition function which however differ in the distribution of operators into sectors and hence in the physical meaning of the operators involved. Related to the projection mechanism in the continuum there are remarkable symmetry properties of the finite XXZ chain. The observed degeneracies in the energy and momentum spectra are shown to be the consequence of intertwining relations involving U_q[sl(2)] quantum algebra transformations.Comment: This is a preprint version (37 pages, LaTeX) of an article published back in 1993. It has been made available here because there has been recent interest in conformal twisted boundary conditions. The "duality-twisted" boundary conditions discussed in this paper are particular examples of such boundary conditions for quantum spin chains, so there might be some renewed interest in these result

Urinary secretion and extracellular aggregation of mutant uromodulin isoforms.

Uromodulin is exclusively expressed in the thick ascending limb and is the most abundant protein secreted in urine where it is found in high-molecular-weight polymers. Its biological functions are still elusive, but it is thought to play a protective role against urinary tract infection, calcium oxalate crystal formation, and regulation of water and salt balance in the thick ascending limb. Mutations in uromodulin are responsible for autosomal-dominant kidney diseases characterized by defective urine concentrating ability, hyperuricemia, gout, tubulointerstitial fibrosis, renal cysts, and chronic kidney disease. Previous in vitro studies found retention in the endoplasmic reticulum as a common feature of all uromodulin mutant isoforms. Both in vitro and in vivo we found that mutant isoforms partially escaped retention in the endoplasmic reticulum and reached the plasma membrane where they formed large extracellular aggregates that have a dominant-negative effect on coexpressed wild-type protein. Notably, mutant uromodulin excretion was detected in patients carrying uromodulin mutations. Thus, our results suggest that mutant uromodulin exerts a gain-of-function effect that can be exerted by both intra- and extracellular forms of the protein

Post-transplant recurrence of steroid resistant nephrotic syndrome in children: the Italian experience

Background: Steroid resistant nephrotic syndrome (SRNS) is a frequent cause of end stage renal disease in children and post-transplant disease recurrence is a major cause of graft loss. Methods: We identified all children with SRNS who underwent renal transplantation in Italy, between 2005 and 2017. Data were retrospectively collected for the presence of a causative gene mutation, sex, histology, duration of pre-transplant dialysis, age at onset and transplant, HLA matching, recurrence, therapy for recurrence, and graft survival. Results: 101 patients underwent a first and 22 a second renal transplant. After a median follow-up of 58.5&nbsp;months, the disease recurred on the first renal transplant in 53.3% of patients with a non-genetic and none with a genetic SRNS. Age at transplant &gt; 9&nbsp;years and the presence of at least one HLA-AB match were independent risk factors for recurrence. Duration of dialysis was longer in children with relapse, but did not reach statistical significance. Overall, 24% of patients lost the first graft, with recurrence representing the commonest cause. Among 22 patients who underwent a second transplant, 5 suffered of SRNS recurrence. SRNS relapsed in 5/9 (55%) patients with disease recurrence in their first transplant and 2 of them lost the second graft. Conclusions: Absence of a causative mutation represents the major risk factor for post-transplant recurrence in children with SRNS, while transplant can be curative in genetic SRNS. A prolonged time spent on dialysis before transplantation has no protective effect on the risk of relapse and should not be encouraged. Retransplantation represents a second chance after graft loss for recurrence