Cheap Talk: Basic Models and New Developments

In this paper a software implementation is proposed of integrated flight mechanics / aeroelastic aircraft models, using object-oriented modeling techniques. Model development involves integrating a rigid aircraft simulation model with aeroelastic flutter analysis models. The main application is primary flight control law design, in which most of the criteria are of flight mechanical nature. For this reason, the rigid aircraft model is taken as the basis, while the fidelity of the aeroelastic part may depend on the accuracy required. Object-oriented modeling allows physical objects and phenomena to be implemented one-to-one into software objects, since interconnections can be defined freely (e.g. according to physical interactions like energy flow). This feature facilitates integration of model components from different engineering disciplines. A model compiler generates simulation code by symbolic manipulation of the model equations. The code can be exported to several (simulation) la..

Daily Work Contexts and Resistance to Organisational Change: The Role of Leader-Member Exchange, Development Climate, and Change Process Characteristics

In the last decade, researchers have started to investigate the psychological processes that are involved in employees’ experiences of organisational change. The present study examined how characteristics of the daily work context related to employees’ resistance to change through aspects of the change process. The results supported the research model, showing that the relationships of leader–member exchange and perceived development climate with employees’ resistance to a merger were fully mediated by three change process characteristics (i.e. information, participation, and trust in management). In addition, two individual-level characteristics (i.e. openness to job changes, and organisational tenure) showed significant relationships with resistance to change. Employees’ role breadth self-efficacy was not related to resistance. Together, the results suggest a number of ways in which organisations can increase the effectiveness of their change efforts. Au cours de la dernière décennie, les chercheurs ont commencéàétudier les processus psychologiques à l’œvre dans les expériences des employés lors d’un changement organisationnel. La présente étude examine la façon dont les caractéristiques d’un contexte de travail quotidien sont en lien avec la résistance au changement des salariés à travers certains aspects du processus de changement. Les résultats confirment le modèle de recherche en montrant que les relations de LMX (Leader–Member Exchange) et du climat de développement perçu avec la résistance des salariés à une fusion étaient totalement médiées par trois caractéristiques processuelles de changement (l’information, la participation et la confiance dans la direction). De plus, les caractéristiques individuelles (ouverture aux changements de travail et titularisation au sein de l’organisation) sont significativement liées à la résistance au changement. L’efficacité de l’ampleur du rôle des salariés n’est pas liée à la résistance. Ensemble, ces résultats ouvrent quelques voies que les organisations peuvent utiliser pour augmenter l’efficacité de leurs efforts de changement

Pathogenic abnormal splicing due to intronic deletions that induce biophysical space constraint for spliceosome assembly

A precise genetic diagnosis is the single most important step for families with genetic disorders to enable personalized and preventative medicine. In addition to genetic variants in coding regions (exons) that can change a protein sequence, abnormal pre-mRNA splicing can be devastating for the encoded protein, inducing a frameshift or in-frame deletion/insertion of multiple residues. Non-coding variants that disrupt splicing are extremely challenging to identify. Stemming from an initial clinical discovery in two index Australian families, we define 25 families with genetic disorders caused by a class of pathogenic non-coding splice variant due to intronic deletions. These pathogenic intronic deletions spare all consensus splice motifs, though they critically shorten the minimal distance between the 5' splice-site (5'SS) and branchpoint. The mechanistic basis for abnormal splicing is due to biophysical constraint precluding U1/U2 spliceosome assembly, which stalls in A-complexes (that bridge the 5'SS and branchpoint). Substitution of deleted nucleotides with non-specific sequences restores spliceosome assembly and normal splicing, arguing against loss of an intronic element as the primary causal basis. Incremental lengthening of 5'SS-branchpoint length in our index EMD case subject defines 45-47 nt as the critical elongation enabling (inefficient) spliceosome assembly for EMD intron 5. The 5'SS-branchpoint space constraint mechanism, not currently factored by genomic informatics pipelines, is relevant to diagnosis and precision medicine across the breadth of Mendelian disorders and cancer genomics.Samantha J.Bryen, Himanshu Joshi, Frances J.Evesson, Cyrille Girard, Roula Ghaoui, Leigh B.Waddell ... et al