Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci

Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis-associated haplotypes at 11 loci. Two ankylosing spondylitis-associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.

Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's Esophagus

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P combined = 4.09 × 10-9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P combined = 2.74 × 10-10; OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus. © 2012 Nature America, Inc. All rights reserved.

Passivity-based Trajectory-tracking for Marine Craft with Disturbance Rejection

This paper presents a Hamiltonian model of marine vehicle dynamics in six degrees of freedom in both body-fixed and inertial momentum coordinates. The model in body-fixed coordinates presents a particular structure of the mass matrix that allows the adaptation and application of passivity-based control interconnection and damping assignment design methodologies developed for robust stabilisation of mechanical systems in terms of generalised coordinates. As an example of application, we follow this methodology to design a passivity-based tracking controller with integral action for fully actuated vehicles in six degrees of freedom. We also describe a momentum transformation that allows an alternative model representation that resembles general port-Hamiltonian mechanical systems with a coordinate dependent mass matrix. This can be seen as an enabling step towards the adaptation of the theory of control of port-Hamiltonian systems developed in robotic manipulators and multi-body mechanical systems to the case of marine craft dynamics.

Smooth stabilisation of nonholonomic robots subject to disturbances

In this paper, we address the problem of stabilisation of robots subject to nonholonommic constraints and external disturbances using port-Hamiltonian theory and smooth time-invariant control laws. This should be contrasted with the commonly used switched or time-varying laws. We propose a control design that provides asymptotic stability of an manifold (also called relative equilibria)-due to the Brockett condition this is the only type of stabilisation possible using smooth time-invariant control laws. The equilibrium manifold can be shaped to certain extent to satisfy specific control objectives. The proposed control law also incorporates integral action, and thus the closed-loop system is robust to unknown constant disturbances. A key step in the proposed design is a change of coordinates not only in the momentum, but also in the position vector, which differs from coordinate transformations previously proposed in the literature for the control of nonholonomic systems. The theoretical properties of the control law are verified via numerical simulation based on a robotic ground vehicle model with differential traction wheels and non co-axial centre of mass and point of contact.

The Relationship Between University Culture and Climate and Research Scientists’ Spin-off Intentions

Over the past decades, universities have increasingly become involved in entrepreneurial activities. Despite efforts to embrace their 'third mission', universities still demonstrate great heterogeneity in terms of their involvement in academic entrepreneurship. This chapter adopts an institutional perspective to understand how organizational characteristics affect research scientists' entrepreneurial intentions. We study the impact of university culture and climate on entrepreneurial intentions, thereby specifically focusing on intentions to spin off a company. Using a sample of 437 research scientists from Swedish and German universities, our results reveal that the extent to which universities articulate entrepreneurship as a fundamental element of their mission fosters research scientists' spin-off intentions. Furthermore, the presence of university role models positively affects research scientists' propensity to engage in entrepreneurial activities, both directly and indirectly through entrepreneurial self-efficacy. Finally, research scientists working at universities which explicitly reward people for 'third mission' related output show higher levels of spin-off intentions. This study has implications for both academics and practitioners, including university managers and policy makers.