Improving the reuse possibilities of the behavioral aspects of object-oriented domain models.

Reuse of domain models is often limited to the reuse of the structural aspects of the domain (e.g. by means of generic data models). In object-oriented models, reuse of dynamic aspects is achieved by reusing the methods of domain classes. Because in the object-oriented approach any behavior is attached to a class, it is impossible to reuse behavior without at the same time reusing the class. In addition, because of the message passing paradigm, object interaction must be specified as a method attached to one class which is invoked by another class. In this way object interaction is hidden in the behavioral aspects of classes. This makes object interaction schemas difficult to reuse and customize. The focus of this paper is on improving the reuse of object-oriented domain models. This is achieved by centering the behavioral aspects around the concept of business events.Model; Models;

E3 Ubiquitin Ligases as Immunotherapeutic Target in Atherosclerotic Cardiovascular Disease

Chronic low-grade inflammation drives atherosclerosis and despite optimal pharmacological treatment of classical cardiovascular risk factors, one third of the patients with atherosclerotic cardiovascular disease has elevated inflammatory biomarkers. Additional anti-inflammatory strategies to target this residual inflammatory cardiovascular risk are therefore required. T-cells are a dominant cell type in human atherosclerotic lesions. Modulation of T-cell activation is therefore a potential strategy to target inflammation in atherosclerosis. Ubiquitination is an important regulatory mechanism of T-cell activation and several E3 ubiquitin ligases, including casitas B-lineage lymphoma proto-oncogene B (Cbl-B), itchy homolog (Itch), and gene related to anergy in lymphocytes (GRAIL), function as a natural brake on T-cell activation. In this review we discuss recent insights on the role of Cbl-B, Itch, and GRAIL in atherosclerosis and explore the therapeutic potential of these E3 ubiquitin ligases in cardiovascular medicine

Like or dislike? Adolescents’ responses to personalized social network site advertising

Increasingly, personal data posted by users of social network sites (SNSs) can be used to personalize advertising. The present study investigates how adolescents respond to personalized ads in terms of attitude toward the ad, brand engagement and intention to forward, and whether privacy concerns moderate their responses. According to pretest results, a medium level of personalization was expected to be optimal in terms of advertising effectiveness. A within-subjects experiment involving 40 participants aged 14–18 years was performed. Three conditions of personalized advertising were designed with, respectively, low, medium, and high levels of personalization. The study found that the highest personalization condition generated the most positive response and that privacy concerns did not moderate the effects of personalization. The privacy paradox is discussed as an alternative explanation, along with other implications of the results

Photometric monitoring of the doubly imaged quasar UM673: possible evidence for chromatic microlensing

We present the results of two-band CCD photometric monitoring of the gravitationally lensed quasar Q 0142-100 (UM 673).The data, obtained at ESO-La Silla with the 1.54 m Danish telescope in the Gunn i-band (October 1998 - September 1999) and in the Johnson V-band (October 1998 to December 2001), were analyzed using three different photometric methods. The light-curves obtained with all methods show variations, with a peak-to-peak amplitude of 0.14 magnitude in $V$. Although it was not possible to measure the time delay between the two lensed QSO images, the brighter component displays possible evidence for microlensing: it becomes bluer as it gets brighter, as expected under the assumption of differential magnification of a quasar accretion diskComment: Accepted for publication in Astronomy & Astrophysics; 8 pages, 7 figure

I. Flux and color variations of the quadruply imaged quasar HE 0435-1223

aims: We present VRi photometric observations of the quadruply imaged quasar HE 0435-1223, carried out with the Danish 1.54m telescope at the La Silla Observatory. Our aim was to monitor and study the magnitudes and colors of each lensed component as a function of time. methods: We monitored the object during two seasons (2008 and 2009) in the VRi spectral bands, and reduced the data with two independent techniques: difference imaging and PSF (Point Spread Function) fitting.results: Between these two seasons, our results show an evident decrease in flux by ~0.2-0.4 magnitudes of the four lensed components in the three filters. We also found a significant increase (~0.05-0.015) in their V-R and R-i color indices. conclusions: These flux and color variations are very likely caused by intrinsic variations of the quasar between the observed epochs. Microlensing effects probably also affect the brightest "A" lensed component.Comment: 10 pages, 8 figure

Inhibition of PFKFB3 Hampers the Progression of Atherosclerosis and Promotes Plaque Stability

Aims: 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)3-mediated glycolysis is pivotal in driving macrophage- and endothelial cell activation and thereby inflammation. Once activated, these cells play a crucial role in the progression of atherosclerosis. Here, we analyzed the expression of PFKFB3 in human atherosclerotic lesions and investigated the therapeutic potential of pharmacological inhibition of PFKFB3 in experimental atherosclerosis by using the glycolytic inhibitor PFK158. Methods and Results: PFKFB3 expression was higher in vulnerable human atheromatous carotid plaques when compared to stable fibrous plaques and predominantly expressed in plaque macrophages and endothelial cells. Analysis of advanced plaques of human coronary arteries revealed a positive correlation of PFKFB3 expression with necrotic core area. To further investigate the role of PFKFB3 in atherosclerotic disease progression, we treated 6–8 weeks old male Ldlr–/– mice. These mice were fed a high cholesterol diet for 13 weeks, of which they were treated for 5 weeks with the glycolytic inhibitor PFK158 to block PFKFB3 activity. The incidence of fibrous cap atheroma (advanced plaques) was reduced in PFK158-treated mice. Plaque phenotype altered markedly as both necrotic core area and intraplaque apoptosis decreased. This coincided with thickening of the fibrous cap and increased plaque stability after PFK158 treatment. Concomitantly, we observed a decrease in glycolysis in peripheral blood mononuclear cells compared to the untreated group, which alludes that changes in the intracellular metabolism of monocyte and macrophages is advantageous for plaque stabilization. Conclusion: High PFKFB3 expression is associated with vulnerable atheromatous human carotid and coronary plaques. In mice, high PFKFB3 expression is also associated with a vulnerable plaque phenotype, whereas inhibition of PFKFB3 activity leads to plaque stabilization. This data implies that inhibition of inducible glycolysis may reduce inflammation, which has the ability to subsequently attenuate atherogenesis

Mycotic pseudoaneurysms complicating renal transplantation: a case series and review of literature

<p>Abstract</p> <p>Introduction</p> <p>Kidney transplantation can be complicated by infection and subsequent development of mycotic aneurysm, endangering the survival of the graft and the patient. Management of this condition in five cases is discussed, accompanied by a review of the relevant literature.</p> <p>Case presentations</p> <p>Five patients, three men 42-, 67- and 57-years-old and two women 55- and 21-years-old (mean age of 48 years), all Caucasians, developed a mycotic aneurysm in the region of the anastomosis between renal graft artery and iliac axes. Four patients presented with systemic fever and iliac fossa pain and one presented with hemorrhagic shock. Morphologic investigation by color doppler ultrasonography revealed a pseudoaneurysm at the anastomotic site. A combination of antibiotic therapy, surgery and interventional procedures was required as all kidney transplants had to be removed. No recurrence was recorded during the follow-up period.</p> <p>Conclusions</p> <p>A high index of suspicion is required for the timely diagnosis of a mycotic aneurysm; aggressive treatment with cover stents and/or surgical excision is necessary in order to prevent potentially fatal complications.</p