Receptor-like protein tyrosine phosphatases: alike and yet so different

Reversible phosphorylation on tyrosine residues is an extremely rapid and powerful posttranslational modification that is used in signalling pathways for the regulation of cell growth and differentiation. Over the past several years an impressive number of receptor-like protein tyrosine phosphatase (RPTPase) family members have been identified by molecular cloning, and undoubtedly many more will follow. This review provides an overview of the molecular data that are available for the currently identified RPTPases and discusses their possible biological implications.     

Relationships between driving simulator performance and driving test results

This article is considered relevant because: 1) car driving is an everyday and safety-critical task; 2) simulators are used to an increasing extent for driver training (related topics: training, virtual reality, human-machine interaction); 3) the article addresses relationships between performance in the simulator and driving test results--a relevant topic for those involved in driver training and the virtual reality industries; 4) this article provides new insights about individual differences in young drivers' behaviour. Simulators are being used to an increasing extent for driver training, allowing for the possibility of collecting objective data on driver proficiency under standardised conditions. However, relatively little is known about how learner drivers' simulator measures relate to on-road driving. This study proposes a theoretical framework that quantifies driver proficiency in terms of speed of task execution, violations and errors. This study investigated the relationships between these three measures of learner drivers' (n=804) proficiency during initial simulation-based training and the result of the driving test on the road, occurring an average of 6 months later. A higher chance of passing the driving test the first time was associated with making fewer steering errors on the simulator and could be predicted in regression analysis with a correlation of 0.18. Additionally, in accordance with the theoretical framework, a shorter duration of on-road training corresponded with faster task execution, fewer violations and fewer steering errors (predictive correlation 0.45). It is recommended that researchers conduct more large-scale studies into the reliability and validity of simulator measures and on-road driving tests.     

Tool support for verifying UML activity diagrams

We describe a tool that supports verification of workflow models specified in UML activity diagrams. The tool translates an activity diagram into an input format for a model checker according to a mathematical semantics. With the model checker, arbitrary propositional requirements can be checked against the input model. If a requirement fails to hold, an error trace is returned by the model checker, which our tool presents by highlighting a corresponding path in the activity diagram. We summarize our formal semantics, discuss the techniques used to reduce an infinite state space to a finite one, and motivate the need for strong fairness constraints to obtain realistic results. We define requirement-preserving rules for state space reduction. Finally, we illustrate the whole approach with a few example verifications.     

Generalised Procrustes Analysis with optimal scaling: Exploring data from a power supplier

Generalised Procrustes Analysis (GPA) is a method for matching several, possibly large, data sets by fitting them to each other using transformations, typically rotations. The linear version of GPA has been applied in a wide range of contexts. A non-linear extension of GPA is developed which uses Optimal Scaling (OS). The approach is suited to match data sets that contain nominal variables. A database of a Dutch power supplier that contains many categorical variables unfit for the usual linear GPA methodology is used to illustrate the approach.     

Expanding complexity in myotonic dystrophy

Myotonic dystrophy (DM) is a highly variable multisystemic disease belonging to the rather special class of trinucleotide expansion disorders. DM results from dynamic expansion of a perfect (CTG)n repeat situated in a gene-dense region on chromosome 19q. Based on findings in patient materials or cellular and animal models, many mechanisms for the causes and consequences of repeat expansion have been proposed; however, none of them has enjoyed prolonged support. There is now circumstantial evidence that long (CTG)n repeats may affect the expression of any of at least three genes, myotonic dystrophy protein kinase (DMPK), DMR-N9 (gene 59), and a DM-associated homeodomain protein (DMAHP). Furthermore, the new findings suggest that DM is not a simple gene-dosage or gain-or-loss-of-function disorder but that entirely new pathological pathways at the DNA, RNA, or protein level may play a role in its manifestation.     

Combined myofibrillar and mitochondrial creatine kinase deficiency impairs mouse diaphragm isotonic function

Creatine kinase (CK) is an enzyme central to cellular high-energy phosphate metabolism in muscle. To characterize the physiological role of CK in respiratory muscle during dynamic contractions, we compared the force-velocity relationships, power, and work output characteristics of the diaphragm (Dia) from mice with combined myofibrillar and sarcomeric mitochondrial CK deficiency (CK[-/-]) with CK-sufficient controls (Ctl). Maximum velocity of shortening was significantly lower in CK[-/-] Dia (14.1 +/- 0.9 Lo/s, where Lo is optimal fiber length) compared with Ctl Dia (17.5 +/- 1.1 Lo/s) (P < 0.01). Maximum power was obtained at 0.4-0.5 tetanic force in both groups; absolute maximum power (2,293 +/- 138 W/m2) and work (201 +/- 9 J/m2) were lower in CK[-/-] Dia compared with Ctl Dia (2,744 +/- 146 W/m2 and 284 +/- 26 J/m2, respectively) (P < 0.05). The ability of CK[-/-] Dia to sustain shortening during repetitive isotonic activation (75 Hz, 330-ms duration repeated each second at 0.4 tetanic force load) was markedly impaired, with CK[-/-] Dia power and work declining to zero by 37 +/- 4 s, compared with 61 +/- 5 s in Ctl Dia. We conclude that combined myofibrillar and sarcomeric mitochondrial CK deficiency profoundly impairs Dia power and work output, underscoring the functional importance of CK during dynamic contractions in skeletal muscle.     

Steps towards a method for the formal modeling of dynamic objects

Fragments of a method to formally specify object-oriented models of a universe of discourse are presented. The task of finding such models is divided into three subtasks, object classification, event specification, and the specification of the life cycle of an object. Each of these subtasks is further subdivided, and for each of the subtasks heuristics are given that can aid the analyst in deciding how to represent a particular aspect of the real world. The main sources of inspiration are Jackson System Development, algebraic specification of data- and object types, and algebraic specification of processes.