Genetics of Tinnitus: Time to Biobank Phantom Sounds

Tinnitus is a common phantom sensation resulting most often from sensory deprivation, and for which little knowledge on the molecular mechanisms exists. While the existing evidence for a genetic influence on the condition has been until now sparse and underpowered, recent data suggest that specific forms of tinnitus have a strong genetic component revealing that not all tinnitus percepts are alike, at least in how they are genetically driven. These new findings pave the way for a better understanding on how phantom sensations are molecularly driven and call for international biobanking efforts

A condensed matter interpretation of SM fermions and gauge fields

We present the bundle Aff(3) x C x /(R^3), with a geometric Dirac equation on it, as a three-dimensional geometric interpretation of the SM fermions. Each C x /(R^3) describes an electroweak doublet. The Dirac equation has a doubler-free staggered spatial discretization on the lattice space Aff(3) x C (Z^3). This space allows a simple physical interpretation as a phase space of a lattice of cells in R^3. We find the SM SU(3)_c x SU(2)_L x U(1)_Y action on Aff(3) x C x /(R^3) to be a maximal anomaly-free special gauge action preserving E(3) symmetry and symplectic structure, which can be constructed using two simple types of gauge-like lattice fields: Wilson gauge fields and correction terms for lattice deformations. The lattice fermion fields we propose to quantize as low energy states of a canonical quantum theory with Z_2-degenerated vacuum state. We construct anticommuting fermion operators for the resulting Z_2-valued (spin) field theory. A metric theory of gravity compatible with this model is presented too.Comment: Minimal modifications in comparison with the published versio

Positivity and conservation of superenergy tensors

Two essential properties of energy-momentum tensors T_{\mu\nu} are their positivity and conservation. This is mathematically formalized by, respectively, an energy condition, as the dominant energy condition, and the vanishing of their divergence \nabla^\mu T_{\mu\nu}=0. The classical Bel and Bel-Robinson superenergy tensors, generated from the Riemann and Weyl tensors, respectively, are rank-4 tensors. But they share these two properties with energy momentum tensors: the Dominant Property (DP) and the divergence-free property in the absence of sources (vacuum). Senovilla defined a universal algebraic construction which generates a basic superenergy tensor T{A} from any arbitrary tensor A. In this construction the seed tensor A is structured as an r-fold multivector, which can always be done. The most important feature of the basic superenergy tensors is that they satisfy automatically the DP, independently of the generating tensor A. In a previous paper we presented a more compact definition of T{A} using the r-fold Clifford algebra. This form for the superenergy tensors allowed to obtain an easy proof of the DP valid for any dimension. In this paper we include this proof. We explain which new elements appear when we consider the tensor T{A} generated by a non-degree-defined r-fold multivector A and how orthogonal Lorentz transformations and bilinear observables of spinor fields are included as particular cases of superenergy tensors. We find some sufficient conditions for the seed tensor A, which guarantee that the generated tensor T{A} is divergence-free. These sufficient conditions are satisfied by some physical fields, which are presented as examples.Comment: 19 pages, no figures. Language and minor changes. Published versio

A convenient coordinatization of Siegel-Jacobi domains

We determine the homogeneous K\"ahler diffeomorphism $FC$ which expresses the K\"ahler two-form on the Siegel-Jacobi ball \mc{D}^J_n=\C^n\times \mc{D}_n as the sum of the K\"ahler two-form on \C^n and the one on the Siegel ball \mc{D}_n. The classical motion and quantum evolution on \mc{D}^J_n determined by a hermitian linear Hamiltonian in the generators of the Jacobi group G^J_n=H_n\rtimes\text{Sp}(n,\R)_{\C} are described by a matrix Riccati equation on \mc{D}_n and a linear first order differential equation in z\in\C^n, with coefficients depending also on W\in\mc{D}_n. $H_n$ denotes the $(2n+1)$-dimensional Heisenberg group. The system of linear differential equations attached to the matrix Riccati equation is a linear Hamiltonian system on \mc{D}_n. When the transform $FC:(\eta,W)\rightarrow (z,W)$ is applied, the first order differential equation in the variable \eta=(\un-W\bar{W})^{-1}(z+W\bar{z})\in\C^n becomes decoupled from the motion on the Siegel ball. Similar considerations are presented for the Siegel-Jacobi upper half plane \mc{X}^J_n=\C^n\times\mc{X}_n, where \mc{X}_n denotes the Siegel upper half plane.Comment: 32 pages, corrected typos, Latex, amsart, AMS font

Algebraic conformal quantum field theory in perspective

Conformal quantum field theory is reviewed in the perspective of Axiomatic, notably Algebraic QFT. This theory is particularly developped in two spacetime dimensions, where many rigorous constructions are possible, as well as some complete classifications. The structural insights, analytical methods and constructive tools are expected to be useful also for four-dimensional QFT.Comment: Review paper, 40 pages. v2: minor changes and references added, so as to match published versio

Analysis of BRAF and NRAS Mutation Status in Advanced Melanoma Patients Treated with Anti-CTLA-4 Antibodies: Association with Overall Survival?

Ipilimumab and tremelimumab are human monoclonal antibodies (Abs) against cytotoxic T-lymphocyte antigen-4 (CTLA-4). Ipilimumab was the first agent to show a statistically significant benefit in overall survival in advanced melanoma patients. Currently, there is no proven association between the BRAFV600 mutation and the disease control rate in response to ipilimumab. This analysis was carried out to assess if BRAFV600 and NRAS mutation status affects the clinical outcome of anti-CTLA-4-treated melanoma patients. This is a retrospective multi-center analysis of 101 patients, with confirmed BRAF and NRAS mutation status, treated with anti-CTLA-4 antibodies from December 2006 until August 2012. The median overall survival, defined from the treatment start date with the anti-CTLA-4. Abs-treatment to death or till last follow up, of BRAFV600 or NRAS mutant patients (n = 62) was 10.12 months (95% CI 6.78-13.2) compared to 8.26 months (95% CI 6.02-19.9) in BRAFV600/NRASwt subpopulation (n = 39) (p = 0.67). The median OS of NRAS mutated patients (n = 24) was 12.1 months and although was prolonged compared to the median OS of BRAF mutated patients (n = 38, mOS = 8.03 months) or BRAFV600/NRASwt patients (n = 39, mOS = 8.26 months) the difference didn't reach statistical significance (p = 0.56). 69 patients were able to complete 4 cycles of anti-CTLA-4 treatment. Of the 24 patients treated with selected BRAF- or MEK-inhibitors, 16 patients received anti-CTLA 4 Abs following either a BRAF or MEK inhibitor with only 8 of them being able to finish 4 cycles of treatment. Based on our results, there is no difference in the median OS in patients treated with anti-CTLA-4 Abs implying that the BRAF/NRAS mutation status alone is not sufficient to predict the outcome of patients treated with anti-CTLA-4 Abs

Surveying Standard Model Flux Vacua on T6/Z2×Z2T^6/Z_2\times Z_2

We consider the SU(2)LxSU(2)R Standard Model brane embedding in an orientifold of T6/Z2xZ2. Within defined limits, we construct all such Standard Model brane embeddings and determine the relative number of flux vacua for each construction. Supersymmetry preserving brane recombination in the hidden sector enables us to identify many solutions with high flux. We discuss in detail the phenomenology of one model which is likely to dominate the counting of vacua. While Kahler moduli stabilization remains to be fully understood, we define the criteria necessary for generic constructions to have fixed moduli.Comment: 30 pages, LaTeX, v2: added reference

Differential influence of vemurafenib and dabrafenib on patients' lymphocytes despite similar clinical efficacy in melanoma

In this study, we demonstrate that vemurafenib but not dabrafenib reduces peripheral lymphocyte counts in melanoma patients while both agents show similar clinical efficacy. Within the lymphocyte compartment, vemurafenib selectively decreases circulating CD4+ T cells and changes their phenotype and function. This indicates that selective BRAFi need to be assessed individually for immunomodulatory effects, especially, when planning combinations with immunotherapie

Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach

Therapeutic treatments for schizophrenia do not alleviate symptoms for all patients and efficacy is limited by common, often severe, side-effects. Genetic studies of disease can identify novel drug targets, and drugs for which the mechanism has direct genetic support have increased likelihood of clinical success. Large-scale genetic studies of schizophrenia have increased the number of genes and gene sets associated with risk. We aimed to examine the overlap between schizophrenia risk loci and gene targets of a comprehensive set of medications to potentially inform and improve treatment of schizophrenia