Declarative Models for Business Processes and UI Generation using OCL

This paper presents an approach to model business processes and associated user interfaces in a declarative way, relying on constraints. An UML-based meta-model to define processes, activities and user-interface objects is proposed. Connecting activities and user interface objects in an integrated model allows expressing interdependencies and mutual effects. Flexible execution logic for workflows and UI control flows are specified by OCL invariants. The model is constructed for the UML tool USE. Using object snapshots, USE can animate and validate business scenarios. Snapshots represent states of a process and a UI at specific times. Such animation enables business process and UI designers to discuss sensible scenarios on basis of the flexible declarative models. The intention is to create validated concrete process models in connection with UI elements that will provide a basis for the system implementation

Extending ASSL: Making UML Metamodel-based Workflows executable

ASSL is a language that enables UML developers to test and certify UML and OCL models [5]. Snapshots of system states are semi-automatically created and main parts of the UML action semantics is implemented by the language. Its interpreter is the well-known UML modeling tool USE. The article proposes a number of language extensions to ASSL. These include (sub ) procedure calls and pre- and postcondition checks on entering and exiting of operations using OCL. The paper motivates the need for these extensions as well as their usage and development along the problem of metamodel-based execution of workflow models. Executable workflow models, driven by ASSL procedures, are introduced in detail to present the usage of ASSL and our extensions

Novel roles for JNK1 in metabolism

Activation of stress-kinase signaling has recently been recognized as an important pathophysiological mechanism in the development of diet-induced obesity, type 2 diabetes mellitus and other aging-related pathologies. Here, c-Jun N-terminal Kinase (JNK) 1 knockout mice have been shown to exhibit protection from diet-induced obesity, glucose intolerance, and insulin resistance. Nonetheless, the tissue-specific role of JNK1-activation in the development of the metabolic syndrome has been poorly defined so far. Recently, it was demonstrated that JNK1 signaling plays a crucial role in the central nervous system (CNS) and in the pituitary to control systemic glucose and lipid metabolism partially through regulation of hormones involved in growth and energy expenditure

Metamodellbasierte und hierarchieorientierte Workflowmodellierung

In dieser Arbeit werden Metamodelle eingesetzt, um Workflow- bzw. Geschäftsprozessmodellierungssprachen und ihre operationale Semantik zu definieren. Mit einer deklarativen und einer hierarchischen Sprache werden zwei Modellierungsweisen verfolgt, die im Bereich der Geschäftsprozessmodellierung nicht weit verbreitet sind. Der Hauptvorteil beim deklarativen Ansatz liegt in einer höheren Flexiblität und bei der hierarchischen Sprache in einer besseren Verständlichkeit der Modelle

Myeloid Cell-Restricted Insulin Receptor Deficiency Protects Against Obesity-Induced Inflammation and Systemic Insulin Resistance

A major component of obesity-related insulin resistance is the establishment of a chronic inflammatory state with invasion of white adipose tissue by mononuclear cells. This results in the release of pro-inflammatory cytokines, which in turn leads to insulin resistance in target tissues such as skeletal muscle and liver. To determine the role of insulin action in macrophages and monocytes in obesity-associated insulin resistance, we conditionally inactivated the insulin receptor (IR) gene in myeloid lineage cells in mice (IRΔmyel-mice). While these animals exhibit unaltered glucose metabolism on a normal diet, they are protected from the development of obesity-associated insulin resistance upon high fat feeding. Euglycemic, hyperinsulinemic clamp studies demonstrate that this results from decreased basal hepatic glucose production and from increased insulin-stimulated glucose disposal in skeletal muscle. Furthermore, IRΔmyel-mice exhibit decreased concentrations of circulating tumor necrosis factor (TNF) α and thus reduced c-Jun N-terminal kinase (JNK) activity in skeletal muscle upon high fat feeding, reflecting a dramatic reduction of the chronic and systemic low-grade inflammatory state associated with obesity. This is paralleled by a reduced accumulation of macrophages in white adipose tissue due to a pronounced impairment of matrix metalloproteinase (MMP) 9 expression and activity in these cells. These data indicate that insulin action in myeloid cells plays an unexpected, critical role in the regulation of macrophage invasion into white adipose tissue and in the development of obesity-associated insulin resistance

Liraglutide restores impaired associative learning in individuals with obesity

Survival under selective pressure is driven by the ability of our brain to use sensory information to our advantage to control physiological needs. To that end, neural circuits receive and integrate external environmental cues and internal metabolic signals to form learned sensory associations, consequently motivating and adapting our behaviour. The dopaminergic midbrain plays a crucial role in learning adaptive behaviour and is particularly sensitive to peripheral metabolic signals, including intestinal peptides, such as glucagon-like peptide 1 (GLP-1). In a single-blinded, randomized, controlled, crossover basic human functional magnetic resonance imaging study relying on a computational model of the adaptive learning process underlying behavioural responses, we show that adaptive learning is reduced when metabolic sensing is impaired in obesity, as indexed by reduced insulin sensitivity (participants: N = 30 with normal insulin sensitivity; N = 24 with impaired insulin sensitivity). Treatment with the GLP-1 receptor agonist liraglutide normalizes impaired learning of sensory associations in men and women with obesity. Collectively, our findings reveal that GLP-1 receptor activation modulates associative learning in people with obesity via its central effects within the mesoaccumbens pathway. These findings provide evidence for how metabolic signals can act as neuromodulators to adapt our behaviour to our body’s internal state and how GLP-1 receptor agonists work in clinics

Exposure to Inhalable, Respirable, and Ultrafine Particles in Welding Fume

This investigation aims to explore determinants of exposure to particle size-specific welding fume. Area sampling of ultrafine particles (UFP) was performed at 33 worksites in parallel with the collection of respirable particles. Personal sampling of respirable and inhalable particles was carried out in the breathing zone of 241 welders. Median mass concentrations were 2.48 mg m−3 for inhalable and 1.29 mg m−3 for respirable particles when excluding 26 users of powered air-purifying respirators (PAPRs). Mass concentrations were highest when flux-cored arc welding (FCAW) with gas was applied (median of inhalable particles: 11.6 mg m−3). Measurements of particles were frequently below the limit of detection (LOD), especially inside PAPRs or during tungsten inert gas welding (TIG). However, TIG generated a high number of small particles, including UFP. We imputed measurements <LOD from the regression equation with manganese to estimate determinants of the exposure to welding fume. Concentrations were mainly predicted by the welding process and were significantly higher when local exhaust ventilation (LEV) was inefficient or when welding was performed in confined spaces. Substitution of high-emission techniques like FCAW, efficient LEV, and using PAPRs where applicable can reduce exposure to welding fume. However, harmonizing the different exposure metrics for UFP (as particle counts) and for the respirable or inhalable fraction of the welding fume (expressed as their mass) remains challenging

Regulation of B cell homeostasis and activation by the tumor suppressor gene CYLD

B cell homeostasis is regulated by multiple signaling processes, including nuclear factor-κB (NF-κB), BAFF-, and B cell receptor signaling. Conditional disruption of genes involved in these pathways has shed light on the mechanisms governing signaling from the cell surface to the nucleus. We describe a novel mouse strain that expresses solely and excessively a naturally occurring splice variant of CYLD (CYLDex7/8 mice), which is a deubiquitinating enzyme that is integral to NF-κB signaling. This shorter CYLD protein lacks the TRAF2 and NEMO binding sites present in full-length CYLD. A dramatic expansion of mature B lymphocyte populations in all peripheral lymphoid organs occurs in this strain. The B lymphocytes themselves exhibit prolonged survival and manifest a variety of signaling disarrangements that do not occur in mice with a complete deletion of CYLD. Although both the full-length and the mutant CYLD are able to interact with Bcl-3, a predominant nuclear accumulation of Bcl-3 occurs in the CYLD mutant B cells. More dramatic, however, is the accumulation of the NF-κB proteins p100 and RelB in CYLDex7/8 B cells, which, presumably in combination with nuclear Bcl-3, results in increased levels of Bcl-2 expression. These findings suggest that CYLD can both positively and negatively regulate signal transduction and homeostasis of B cells in vivo, depending on the expression of CYLD splice variants

Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue

Previous work indicated that lysine-specific demethylase 1 (Lsd1) can positively regulate the oxidative and thermogenic capacities of white and beige adipocytes. Here we investigate the role of Lsd1 in brown adipose tissue (BAT) and find that BAT- selective Lsd1 ablation induces a shift from oxidative to glycolytic metabolism. This shift is associated with downregulation of BAT-specific and upregulation of white adipose tissue (WAT)-selective gene expression. This results in the accumulation of di- and triacylglycerides and culminates in a profound whitening of BAT in aged Lsd1- deficient mice. Further studies show that Lsd1 maintains BAT properties via a dual role. It activates BAT-selective gene expression in concert with the transcription factor Nrf1 and represses WAT-selective genes through recruitment of the CoREST complex. In conclusion, our data uncover Lsd1 as a key regulator of gene expression and metabolic function in BAT