The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis

Although necrosis and necroinflammation are central features of many liver diseases, the role of programmed necrosis in the context of inflammation-dependent hepatocellular death remains to be fully determined. Here, we have demonstrated that the pseudokinase mixed lineage kinase domain-like protein (MLKL), which plays a key role in the execution of receptor interacting protein (RIP) lcinase-dependent necroptosis, is upregulated and activated in human autoimmune hepatitis and in a murine model of inflammation-dependent hepatitis. Using genetic and pharmacologic approaches, we determined that hepatocellular necrosis in experimental hepatitis is driven by an MLKL-dependent pathway that occurs independently of RIPK3. Moreover, we have provided evidence that the cytotoxic activity of the proinflammatory cytokine IFN-gamma in hepatic inflammation is strongly connected to induction of MLKL expression via activation of the transcription factor STAT1. In summary, our results reveal a pathway for MLKL-dependent programmed necrosis that is executed in the absence of RIPK3 and potentially drives the pathogenesis of severe liver diseases

Novel Electroweak Symmetry Breaking Conditions From Quantum Effects In The MSSM

We present, in the context of the Minimal Supersymmetric Standard Model, a detailed one-loop analytic study of the minimization conditions of the effective potential in the Higgs sector. Special emphasis is put on the role played by $Str M^4$ in the determination of the electroweak symmetry breaking conditions, where first and second order derivatives of the effective potential are systematically taken into account. Novel, necessary (and sufficient in the Higgs sector) model-independent constraints, are thus obtained analytically, leading to new theoretical lower and upper bounds on $\tan \beta$. Although fully model-independent, these bounds are found to be much more restrictive than the existing model-dependent ones! A first illustration is given in the context of a SUGRA-GUT motivated scenario.Comment: Latex, 45 pages, 5 figure

Transformation of context-dependent sensory dynamics into motor behavior

Latorre R, Levi R, Varona P (2013) Transformation of Context-dependent Sensory Dynamics into Motor Behavior. PLoS Comput Biol 9(2): e1002908. doi:10.1371/journal.pcbi.1002908The intrinsic dynamics of sensory networks play an important role in the sensory-motor transformation. In this paper we use conductance based models and electrophysiological recordings to address the study of the dual role of a sensory network to organize two behavioral context-dependent motor programs in the mollusk Clione limacina. We show that: (i) a winner take-all dynamics in the gravimetric sensory network model drives the typical repetitive rhythm in the wing central pattern generator (CPG) during routine swimming; (ii) the winnerless competition dynamics of the same sensory network organizes the irregular pattern observed in the wing CPG during hunting behavior. Our model also shows that although the timing of the activity is irregular, the sequence of the switching among the sensory cells is preserved whenever the same set of neurons are activated in a given time window. These activation phase locks in the sensory signals are transformed into specific events in the motor activity. The activation phase locks can play an important role in motor coordination driven by the intrinsic dynamics of a multifunctional sensory organThis work was supported by MINECO TIN2012-30883 and IPT-2011-0727-020000

Planck Scale Symmetry Breaking and Majoron Physics

Majoron models provide neutrino masses via the spontaneous breaking of a global $U(1)$ symmetry. However, it may be argued that all global symmetries will be explicitly violated by gravitational effects. We show that it is possible to preserve most of the usual features of majoron models by invoking $U(1)_{B-L}$ to be a gauge symmetry and adding a second singlet scalar field. The majoron gets a small model dependent mass. The couplings of majorons to neutrinos may be of ordinary strength or may be made arbitrarily weak. We discuss the cosmological and astrophysical consequences of majoron models in the context of a model dependent majoron mass and neutrino coupling. For an appropriate choice of parameters majorons can play the role of dark matter.Comment: 30 pages, UM-TH-92-3

The Renormalization Group, Systems of Units and the Hierarchy Problem

In the context of the Renormalization Group (RG) for gravity I discuss the role of field rescalings and their relation to choices of units. I concentrate on a simple Higgs model coupled to gravity, where natural choices of units can be based on Newton's constant or on the Higgs mass. These quantities are not invariant under the RG, and the ratio between the units is scale-dependent. In the toy model, strong RG running occurs in the intermediate regime between the Higgs and the Planck scale, reproducing the results of the Randall-Sundrum I model. Possible connections with the problem of the mass hierarchy are pointed out.Comment: Plain TEX, 16 pages. Some revisions, some references adde

BRST symmetry for Regge-Teitelboim based minisuperspace models

The Einstein-Hilbert action in the context of Higher derivative theories is considered for finding out their BRST symmetries. Being a constraint system, the model is transformed in the minisuperspace language with the FRLW background and the gauge symmetries are explored. Exploiting the first order formalism developed by Banerjee et. al. the diffeomorphism symmetry is extracted. From the general form of the gauge transformations of the field, the analogous BRST transformations are calculated. The effective Lagrangian is constructed by considering two gauge fixing conditions. Further, the BRST (conserved) charge is computed which plays an important role in defining the physical states from the total Hilbert space of states. The finite field dependent BRST (FFBRST) formulation is also studied in this context where the Jacobian for functional measure is illustrated specifically.Comment: 16 pages, title changed, revised version, to appear in EPJ

Bell violation in the Sky

In this work, we have studied the possibility of setting up Bell's inequality violating experiment in the context of cosmology, based on the basic principles of quantum mechanics. First we start with the physical motivation of implementing the Bell's inequality violation in the context of cosmology. Then to set up the cosmological Bell violating test experiment we introduce a model independent theoretical framework using which we have studied the creation of new massive particles by implementing the WKB approximation method for the scalar fluctuations in presence of additional time dependent mass contribution. Next using the background scalar fluctuation in presence of new time dependent mass contribution, we explicitly compute the expression for the one point and two point correlation functions. Furthermore, using the results for one point function we introduce a new theoretical cosmological parameter which can be expressed in terms of the other known inflationary observables and can also be treated as a future theoretical probe to break the degeneracy amongst various models of inflation. Additionally, we also fix the scale of inflation in a model independent way without any prior knowledge of primordial gravitational waves. Next, we also comment on the technicalities of measurements from isospin breaking interactions and the future prospects of newly introduced massive particles in cosmological Bell violating test experiment. Further, we cite a precise example of this set up applicable in the context of string theory motivated axion monodromy model. Then we comment on the explicit role of decoherence effect and high spin on cosmological Bell violating test experiment. In fine, we provide a theoretical bound on the heavy particle mass parameter for scalar fields, graviton and other high spin fields from our proposed setup.Comment: 202 pages, 16 figures, 1 table, Accepted for publication in European Physical Journal

Speaker-normalized sound representations in the human auditory cortex

The acoustic dimensions that distinguish speech sounds (like the vowel differences in “boot” and “boat”) also differentiate speakers’ voices. Therefore, listeners must normalize across speakers without losing linguistic information. Past behavioral work suggests an important role for auditory contrast enhancement in normalization: preceding context affects listeners’ perception of subsequent speech sounds. Here, using intracranial electrocorticography in humans, we investigate whether and how such context effects arise in auditory cortex. Participants identified speech sounds that were preceded by phrases from two different speakers whose voices differed along the same acoustic dimension as target words (the lowest resonance of the vocal tract). In every participant, target vowels evoke a speaker-dependent neural response that is consistent with the listener’s perception, and which follows from a contrast enhancement model. Auditory cortex processing thus displays a critical feature of normalization, allowing listeners to extract meaningful content from the voices of diverse speakers

Designing role-based view for object-relational databases

In a federated database system, a view mechanism is crucial since it is used to define exportable subsets of data ; to perform a virtual restructuring d ataset; and to construct the integrated schema. The view service in federated databa se systems must be capable of retaining as much semantic information as possible. The object-oriented ( 0 - 0 ) model was considered the suitable canonical data model since it meets the original criteria for canonical model selection. However, with the emergence of stronger object-relational (0 -R ) model, the re is a clear argument for using an 0 - R canonical model in the federation. Hence, research should now focus on th e development of semantically powerful view mechanism for th e newer model. Meanwhile, the availability of real 0 -R technologies offers researchers the opportunity to develop different forms of view mechanisms. The concept of roles has been widely studied in 0 - 0 modelling and development. The role model represents some characteristics that the traditional 0-0 model lacked, such as object migration, multiple occurrences and context-dependent access. While many forms of 0-0 views were designed for the 0-0 canonical model, one option was to extend the 0-0 model to incorporate a role model. In a role model, the real entity is modelled in the form of a role rather than an object. An object represents the permanent properties of an entity is a root object; and an object represents the temporary properties of an entity is a role object. The contribution of this research is to design a view system that employees the concept of roles for the 0 -R canonical model in a federated database system. In this thesis, an examination of the current 0 -R metamodel is provided first in order to provide an environment for recognising the roleview metadata and measuring the view performance; then a Roleview Definition Language (RDL) is introduced, along with the semantics for defining virtual classes and generating virtua l extents; finally, a working prototype is provided to prove th e role-based view system is implementable and the syntax is semantically correct