CARD8 and NLRP1 Undergo Autoproteolytic Processing through a ZU5-Like Domain

The “Function to Find Domain” (FIIND)-containing proteins CARD8 (Cardinal; Tucan) and NLRP1 (NALP1; NAC) are well known components of inflammasomes, multiprotein complexes responsible for activation of caspase-1, a regulator of inflammation and innate immunity. Although identified many years ago, the role of the FIIND is unknown. Here, we report that CARD8 and NLRP1 undergo autoproteolytic cleavage at a conserved SF/S motif within the FIIND. Using bioinformatics and computational modeling approaches, we detected striking structural similarity between the FIIND and the ZU5-UPA domain present in the autoproteolytic protein PIDD. This allowed us to generate a three-dimensional model and to gain insights in the molecular mechanism of the cleavage. Site-directed mutagenesis experiments revealed that the second serine of the SF/S motif is required for CARD8 and NLRP1 autoproteolysis. Furthermore, we discovered an important function for conserved glutamic acid and histidine residues, located in proximity of the cleavage site in regulating the autoprocessing efficiency. Altogether, these results identify a function for the FIIND and show that CARD8 and NLRP1 are ZU5-UPA domain-containing autoproteolytic proteins, thus suggesting a novel mechanism for regulating innate immune responses

Modeling nuclei of radio galaxies from VLBI radio observations. Application to the BL Lac Object S5 1803+784

We present a new method to fit the variations of both coordinates of a VLBI component as a function of time, assuming that the nucleus of the radio source contains a binary black hole system (BBH system). The presence of a BBH system produces 2 perturbations of the trajectory of the ejected VLBI components. By using only the VLBI coordinates, the problem we have to solve reduces to an astrometric problem. Knowledge of the variations of the VLBI coordinates as a function of time contains the kinematical information, thus we are able to deduce the inclination angle of the source and the bulk Lorentz factor of the ejected component. Generally, there is a family of the BBH system producing the same fit to our data. To illustrate this method, we apply it to the source 1807+784. We find that the inclination of the source is i = 5.8+-1.8 degrees and the VLBI component is ejected with a bulk Lorentz factor of 3.7+-0.3. We determine the family of the BBH system which provides the best fit, assuming at first that the masses of the 2 black holes are equal and then that the masses are different. Each family of BBH systems is characterized by Tp/Tb~1.967, where Tp and Tb are the precession period of the accretion disk of the black hole ejecting the VLBI component and the orbiting period of the BBH system.Comment: 15 pages, 12 figure

Optimization of Convex Risk Functions

We consider optimization problems involving convex risk functions. By employing techniques of convex analysis and optimization theory in vector spaces of measurable functions we develop new representation theorems for risk models, and optimality and duality theory for problems involving risk functions

The kinematics in the pc-scale jets of AGN The case of S5 1803+784

We present a kinematic analysis of jet component motion in the VLBI jet of the BL Lac object S5 1803+784, which does not reveal long-term outward motion for most of the components. Understanding the complex kinematic phenomena can possibly provide insights into the differences between quasars and BL Lac objects. The blazar S5 1803+784 has been studied with VLBI at $\nu$ =1.6, 2.3, 5, 8.4, and 15 GHz between 1993.88 and 2005.68 in 26 observing runs. We (re)analyzed the data and present Gaussian model-fits. We collected the already published kinematic information for this source from the literature and re-identified the components according to the new scenario presented in this paper. Altogether, 94 epochs of observations have been investigated. A careful study of the long-term kinematics reveals a new picture for component motion in S5 1803+784. In contrast to previously discussed motion scenarios, we find that the jet structure within 12 mas of the core can most easily be described by the coexistence of several bright jet features that remain on the long-term at roughly constant core separations (in addition to the already known {\it stationary} jet component $\sim$ 1.4 mas) and one faint component moving with an apparent superluminal speed ($\sim$ 19c, based on 3 epochs). While most of the components maintain long-term roughly constant distances from the core, we observe significant, smooth changes in their position angles. We report on an evolution of the whole jet ridge line with time over the almost 12 years of observations. The width of the jet changes periodically with a period of $\sim$ 8 to 9 years. We find a correlation between changes in the position angle and maxima in the total flux-density. We present evidence for a geometric origin of the phenomena and discuss possible models.Comment: The manuscript will be published by A&