Communicating Java Threads

The incorporation of multithreading in Java may be considered a significant part of the Java language, because it provides udimentary facilities for concurrent programming. However, we belief that the use of channels is a fundamental concept for concurrent programming. The channel approach as described in this paper is a realization of a systematic design method for concurrent programming in Java based on the CSP paradigm. CSP requires the availability of a Channel class and the addition of composition constructs for sequential, parallel and alternative processes. The Channel class and the constructs have been implemented in Java in compliance with the definitions in CSP. As a result, implementing communication between processes is facilitated, enabling the programmer to avoid deadlock more easily, and freeing the programmer from synchronization and scheduling constructs. The use of the Channel class and the additional constructs is illustrated in a simple application

Dimensions of professional competences for interventions towards sustainability

This paper investigates sustainability competences through the eyes of professional practitioners in the field of sustainability and presents empirical data that have been created using an action research approach. The design of the study consists of two workshops, in which professional practitioners in interaction with each other and the facilitators are invited to explore and reflect on the specific knowledge, skills, attitudes and behaviours necessary to conduct change processes successfully towards sustainability in a variety of business and professional contexts. The research focuses on the competences associated with these change processes to devise, propose and conduct appropriate interventions that address sustainability issues. Labelled ‘intervention competence’, this ability comprises an interlocking set of knowledge, skills, attitudes and behaviours that include: appreciating the importance of (trying to) reaching decisions or interventions; being able to learn from lived experience of practice and to connect such learning to one’s own scientific knowledge; being able to engage in political-strategic thinking, deliberations and actions, related to different perspectives; the ability for showing goal-oriented, adequate action; adopting and communicating ethical practices during the intervention process; being able to cope with the degree of complexity, and finally being able to translate stakeholder diversity into collectively produced interventions (actions) towards sustainability. Moreover, this competence has to be practised in contexts of competing values, non-technical interests and power relations. The article concludes with recommendations for future research and practice

Utilizing international networks for accelerating research and learning in transformational sustainability science

A promising approach for addressing sustainability problems is to recognize the unique conditions of a particular place, such as problem features and solution capabilities, and adopt and adapt solutions developed at other places around the world. Therefore, research and teaching in international networks becomes critical, as it allows for accelerating learning by sharing problem understandings, successful solutions, and important contextual considerations. This article identifies eight distinct types of research and teaching collaborations in international networks that can support such accelerated learning. The four research types are, with increasing intensity of collaboration: (1) solution adoption; (2) solution consultation; (3) joint research on different problems; and (4) joint research on similar problems. The four teaching types are, with increasing intensity of collaboration: (1) adopted course; (2) course with visiting faculty; (3) joint course with traveling faculty; and (4) joint course with traveling students. The typology is illustrated by extending existing research and teaching projects on urban sustainability in the International Network of Programs in Sustainability, with partner universities from Europe, North America, Asia, and Africa. The article concludes with challenges and strategies for extending individual projects into collaborations in international networks.Postprint (author's final draft

Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure

<p>Abstract</p> <p>Background</p> <p>Progressive remodeling after myocardial infarction (MI) is a leading cause of morbidity and mortality. Recently, glucagon-like peptide (GLP)-1 was shown to have cardioprotective effects, but treatment with GLP-1 is limited by its short half-life. It is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4), an enzyme which inhibits GLP-1 activity. We hypothesized that the DPP-4 inhibitor vildagliptin will increase levels of GLP-1 and may exert protective effects on cardiac function after MI.</p> <p>Methods</p> <p>Sprague-Dawley rats were either subjected to coronary ligation to induce MI and left ventricular (LV) remodeling, or sham operation. Parts of the rats with an MI were pre-treated for 2 days with the DPP-4 inhibitor vildagliptin (MI-Vildagliptin immediate, MI-VI, 15 mg/kg/day). The remainder of the rats was, three weeks after coronary artery ligation, subjected to treatment with DPP-4 inhibitor vildagliptin (MI-Vildagliptin Late, MI-VL) or control (MI). At 12 weeks, echocardiography and invasive hemodynamics were measured and molecular analysis and immunohistochemistry were performed.</p> <p>Results</p> <p>Vildagliptin inhibited the DPP-4 enzymatic activity by almost 70% and increased active GLP-1 levels by about 3-fold in plasma in both treated groups (p < 0.05 vs. non-treated groups). Cardiac function (ejection fraction) was decreased in all 3 MI groups compared with Sham group (p < 0.05); treatment with vildagliptin, either early or late, did not reverse cardiac remodeling. ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide) mRNA levels were significantly increased in all 3 MI groups, but no significant reductions were observed in both vildagliptin groups. Vildagliptin also did not change cardiomyocyte size or capillary density after MI. No effects were detected on glucose level and body weight in the post-MI remodeling model.</p> <p>Conclusion</p> <p>Vildagliptin increases the active GLP-1 level via inhibition of DPP-4, but it has no substantial protective effects on cardiac function in this well established long-term post-MI cardiac remodeling model.</p

Regulation of the (pro)renin-renin receptor in cardiac remodelling

The (pro)reninrenin receptor [(P)RR] was discovered as an important novel component of the reninangiotensin system (RAS). The functional significance of (P)RR is widely studied in renal and vascular pathologies and has sparked interest for a potential role in cardiovascular disease. To investigate the role of (P)RR in cardiac pathophysiology, we aimed to assess (P)RR regulation in adverse cardiac remodelling of the failing heart. In particular, we evaluated the expression of (P)RR in different models of heart failure and across different species. Significantly increased levels of (P)RR mRNA were found in post-myocardial infarcted (MI) hearts of rats (1.6-fold, P <0.05) and mice (5-fold, P <0.01), as well as in transgenic rats with overexpression of the mouse renin gene (Ren2) (2.2-fold, P <0.01). Moreover, we observed a strong increase of (P)RR expression in hearts of dilated cardiomyopathy (DCM) patients (5.3-fold, P <0.001). Because none of the tested commercially available antibodies appeared to detect endogenous (P)RR, a (P)RR-specific polyclonal antibody was generated to study (P)RR protein levels. (P)RR protein levels were significantly increased in the post-MI rat heart (1.4-fold, P <0.05) as compared to controls. Most interestingly in DCM patients, a significant 8.7-fold (P <0.05) increase was observed. Thus, protein expression paralleled gene expression. These results demonstrate that (P)RR expression is strongly up-regulated both in rodent models of heart failure and in the failing human heart, hinting to a potential role for (P)RR in cardiac pathophysiology

Therapeutic potential of erythropoietin in cardiovascular disease:Erythropoiesis and beyond

Erythropoietin (EPO) is a glycoprotein hormone implicated in the regutation of red blood cell production. Anemia is common in chronic heart failure (CHF) patients and associated with an inappropriately low EPO-production, suggesting a role for its recombinant human form (rhEPO) in treatment. Although safety concerns have been raised regarding treatment with rhEPO in patients with chronic kidney disease, treatment with rhEPO in patients with CHF has so far been safe and well tolerated. The effect of rhEPO on outcome in anemic CHF patients is under investigation in a phase III clinical trial. In addition to its erythropoietic effects, EPO has been detected in the cardiovascular system, fueling intense research into possible non-hematopoietic effects. EPO has been shown to exert protective effects on the heart during acute myocardial ischemia and improve cardiac function in experimental CHF. Acute protection is mediated through reduction of apoptotic cell death. Improvement of cardiac function in CHF is related to myocardial neovascularization. EPO exhibits a vast array of beneficial effects in cardiovascular disease. In addition to the correction of anemia in CHF, rhEPO might benefit patients with cardiovascular disease

Hypertrophy induced KIF5B controls mitochondrial localization and function in neonatal rat cardiomyocytes

AbstractCardiac hypertrophy is associated with growth and functional changes of cardiomyocytes, including mitochondrial alterations, but the latter are still poorly understood. Here we investigated mitochondrial function and dynamic localization in neonatal rat ventricular cardiomyocytes (NRVCs) stimulated with insulin like growth factor 1 (IGF1) or phenylephrine (PE), mimicking physiological and pathological hypertrophic responses, respectively.A decreased activity of the mitochondrial electron transport chain (ETC) (state 3) was observed in permeabilized NRVCs stimulated with PE, whereas this was improved in IGF1 stimulated NRVCs. In contrast, in intact NRVCs, mitochondrial oxygen consumption rate (OCR) was increased in PE stimulated NRVCs, but remained constant in IGF1 stimulated NRVCs. After stimulation with PE, mitochondria were localized to the periphery of the cell. To study the differences in more detail, we performed gene array studies. IGF1 and PE stimulated NRVCs did not reveal major differences in gene expression of mitochondrial encoding proteins, but we identified a gene encoding a motor protein implicated in mitochondrial localization, kinesin family member 5b (Kif5b), which was clearly elevated in PE stimulated NRVCs but not in IGF1 stimulated NRVCs. We confirmed that Kif5b gene and protein expression were elevated in animal models with pathological cardiac hypertrophy. Silencing of Kif5b reverted the peripheral mitochondrial localization in PE stimulated NRVCs and diminished PE induced increases in mitochondrial OCR, indicating that KIF5B dependent localization affects cellular responses to PE stimulated NRVCs.These results indicate that KIF5B contributes to mitochondrial localization and function in cardiomyocytes and may play a role in pathological hypertrophic responses in vivo

Emerging role of liver X receptors in cardiac pathophysiology and heart failure

Liver X receptors (LXRs) are master regulators of metabolism and have been studied for their pharmacological potential in vascular and metabolic disease. Besides their established role in metabolic homeostasis and disease, there is mounting evidence to suggest that LXRs may exert direct beneficial effects in the heart. Here, we aim to provide a conceptual framework to explain the broad mode of action of LXRs and how LXR signaling may be an important local and systemic target for the treatment of heart failure. We discuss the potential role of LXRs in systemic conditions associated with heart failure, such as hypertension, diabetes, and renal and vascular disease. Further, we expound on recent data that implicate a direct role for LXR activation in the heart, for its impact on cardiomyocyte damage and loss due to ischemia, and effects on cardiac hypertrophy, fibrosis, and myocardial metabolism. Taken together, the accumulating evidence supports the notion that LXRs may represent a novel therapeutic target for the treatment of heart failure