Innate Immunity and Resistance to Tolerogenesis in Allotransplantation

The development of immunosuppressive drugs to control adaptive immune responses has led to the success of transplantation as a therapy for end-stage organ failure. However, these agents are largely ineffective in suppressing components of the innate immune system. This distinction has gained in clinical significance as mounting evidence now indicates that innate immune responses play important roles in the acute and chronic rejection of whole organ allografts. For instance, whereas clinical interest in natural killer (NK) cells was once largely confined to the field of bone marrow transplantation, recent findings suggest that these cells can also participate in the acute rejection of cardiac allografts and prevent tolerance induction. Stimulation of Toll-like receptors (TLRs), another important component of innate immunity, by endogenous ligands released in response to ischemia/reperfusion is now known to cause an inflammatory milieu favorable to graft rejection and abrogation of tolerance. Emerging data suggest that activation of complement is linked to acute rejection and interferes with tolerance. In summary, the conventional wisdom that the innate immune system is of little importance in whole organ transplantation is no longer tenable. The addition of strategies that target TLRs, NK cells, complement, and other components of the innate immune system will be necessary to eventually achieve long-term tolerance to human allograft recipients

Modelling the unfolding pathway of biomolecules: theoretical approach and experimental prospect

We analyse the unfolding pathway of biomolecules comprising several independent modules in pulling experiments. In a recently proposed model, a critical velocity $v_{c}$ has been predicted, such that for pulling speeds $v>v_{c}$ it is the module at the pulled end that opens first, whereas for $v<v_{c}$ it is the weakest. Here, we introduce a variant of the model that is closer to the experimental setup, and discuss the robustness of the emergence of the critical velocity and of its dependence on the model parameters. We also propose a possible experiment to test the theoretical predictions of the model, which seems feasible with state-of-art molecular engineering techniques.Comment: Accepted contribution for the Springer Book "Coupled Mathematical Models for Physical and Biological Nanoscale Systems and Their Applications" (proceedings of the BIRS CMM16 Workshop held in Banff, Canada, August 2016), 16 pages, 6 figure

How do paediatricians use and monitor antithyroid drugs in the UK? A clinician survey

Objective We aimed to document current practice in the medical management of paediatric hyperthyroidism in the UK and compare to international recommendations. Design A 27‐question online survey distributed via an electronic newsletter in August 2018. Participants Responses from 48 members (11%) of the British Society for Paediatric Endocrinology and Diabetes. Measurements Information about antithyroid drug (ATD) preference, treatment duration, monitoring of full blood count (FBC), management of neutropaenia, agranulocytosis screening and patient education. Results Carbimazole is favoured by 98% of respondents and a “dose titration” regimen preferred over “block and replace” (65% vs 29%). TRAbs (thyroid‐stimulating hormone receptor antibodies) are used for diagnostic purposes by 85% and by 33% to look for evidence of disease remission. The majority (81%) treat for a minimum of 2 years before considering a trial off ATD. All respondents reported that they “always/usually” warn their patients about the risk of agranulocytosis before starting ATD, but written information is “rarely/never” provided by 63%. Sore throat (98%) and fever (92%) are the most commonly cited symptoms used to alert a patient to possible agranulocytosis. FBC is measured prior to treatment by 65% and measured periodically during treatment by 70%. Conclusions The management of paediatric hyperthyroidism with ATDs in the UK is not consistent with all international recommendations because a block and replace ATD regimen remains widely used. TRAbs are utilized at presentation, but underused for detecting disease remission. National consensus guidelines and written patient information may refine the management of paediatric patients on ATDs

Non-chiral current algebras for deformed supergroup WZW models

We study deformed WZW models on supergroups with vanishing Killing form. The deformation is generated by the isotropic current-current perturbation which is exactly marginal under these assumptions. It breaks half of the global isometries of the original supergroup. The current corresponding to the remaining symmetry is conserved but its components are neither holomorphic nor anti-holomorphic. We obtain the exact two- and three-point functions of this current and a four-point function in the first two leading orders of a 1/k expansion but to all orders in the deformation parameter. We further study the operator product algebra of the currents, the equal time commutators and the quantum equations of motion. The form of the equations of motion suggests the existence of non-local charges which generate a Yangian. Possible applications to string theory on Anti-de Sitter spaces and to condensed matter problems are briefly discussed.Comment: 43 pages, Latex, one eps figure; v.2: minor corrections, a reference adde

First-principles derivation of the AdS/CFT Y-systems

We provide a first-principles, perturbative derivation of the AdS5/CFT4 Y-system that has been proposed to solve the spectrum problem of N=4 SYM. The proof relies on the computation of quantum effects in the fusion of some loop operators, namely the transfer matrices. More precisely we show that the leading quantum corrections in the fusion of transfer matrices induce the correct shifts of the spectral parameter in the T-system. As intermediate steps we study UV divergences in line operators up to first order and compute the fusion of line operators up to second order for the pure spinor string in AdS5xS5. We also argue that the derivation can be easily extended to other integrable models, some of which describe string theory on AdS4, AdS3 and AdS2 spacetimes.Comment: 45 pages, 5 figures; v2: minor additions, JHEP versio

The conformal current algebra on supergroups with applications to the spectrum and integrability

We compute the algebra of left and right currents for a principal chiral model with arbitrary Wess-Zumino term on supergroups with zero Killing form. We define primary fields for the current algebra that match the affine primaries at the Wess-Zumino-Witten points. The Maurer-Cartan equation together with current conservation tightly constrain the current-current and current-primary operator product expansions. The Hilbert space of the theory is generated by acting with the currents on primary fields. We compute the conformal dimensions of a subset of these states in the large radius limit. The current algebra is shown to be consistent with the quantum integrability of these models to several orders in perturbation theory.Comment: 45 pages. Minor correction