Alteration of early dendritic cell activation by cancer cell lines predisposes immunosuppression, which cannot be reversed by TLR4 stimulation

Dendritic cells (DCs) have shown promise for use in cancer vaccine and cancer immunotherapy studies. However, we demonstrate that cancer cell lines can negatively interfere with DC generation in granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived cultures, although cancer cells are able to enhance CD80 cell surface activation marker and cytokine secretion. Furthermore, in the presence of cancer cells, GM-CSF-derived DCs are unable to stimulate T-cells. Additional stimulation with toll-like receptor 4 cannot fully reverse the suppressive effect of cancer cells or supernatant. Hence, it is imperative to understand the immunosuppressive effects of cancer on DCs in order for DC-based cancer immunotherapy to be successful

Distributed Diagnosis of Actuator and Sensor Faults in HVAC Systems

This paper presents a model-based methodology for diagnosing actuator and sensor faults affecting the temperature dynamics of a multi-zone heating, ventilating and air-conditioning (HVAC) system. By considering the temperature dynamics of the HVAC system as a network of interconnected subsystems, a distributed fault diagnosis architecture is proposed. For every subsystem, we design a monitoring agent that combines local and transmitted information from its neighboring agents in order to provide a decision on the type, number and location of the faults. The diagnosis process of each agent is realized in three steps. Firstly, the agent performs fault detection using a distributed nonlinear estimator. After the detection, the local fault identification is activated to infer the type of the fault using two distributed adaptive estimation schemes and a combinatorial decision logic. In order to distinguish between multiple local faults and propagated sensor faults, a distributed fault isolation is applied using the decisions of the neighboring agents. Simulation results of a 5-zone HVAC system are used to illustrate the effectiveness of the proposed methodology

Prognostic implications of myocardial perfusion imaging and coronary calcium score in a Macedonian cohort of asymptomatic patients with type 2 diabetes

Aim: Type 2 diabetes is a risk factor for coronary artery disease; however, a number of studies have shown that patients are asymptomatic for coronary artery disease. The presence of coronary artery disease in asymptomatic patients with type 2 diabetes was evaluated to determine its impact on management decision and prognosis. Methods: A total of 75 patients underwent single-photon emission computed tomography myocardial perfusion imaging for detection of suspected coronary artery disease. We used 17-segment model for perfusion and function analysis. Multislice computed tomography was performed in 45 patients to assess coronary artery calcium. Complete laboratory analyses with lipid values and standard risk factors were analysed. Forward logistic regression analysis was used to assess predictive parameters for myocardial ischaemia during the follow-up period of 20 ± 4 months. Results and Conclusion: Silent myocardial ischaemia and subclinical coronary artery disease can be detected in a significant proportion of asymptomatic patients with type 2 diabetes. Diabetic patients with normal myocardial perfusion imaging had an excellent 2-year prognosis with optimal medical therapy and intensive risk factor control. In comparison, an abnormal myocardial perfusion imaging led to an increased risk of cardiovascular events. Myocardial perfusion imaging and coronary artery calcium are valuable tools for risk stratification and optimal treatment decision in this asymptomatic diabetic cohort of Macedonian patients. </jats:sec

Diversity of human skeletal muscle in health and disease: contribution of proteomics

Muscle represents a large fraction of the human body mass. It is an extremely heterogeneous tissue featuring in its contractile structure various proportions of heavy- and light-chain slow type 1 and fast types 2A and 2X myosins, actins, tropomyosins, and troponin complexes as well as metabolic proteins (enzymes and most of the players of the so-called excitation-transcription coupling). Muscle is characterized by wide plasticity, i.e. capacity to adjust size and functional properties in response to endogenous and exogenous influences. Over the last decade, proteomics has become a crucial technique for the assessment of muscle at the molecular level and the investigation of its functional changes. Advantages and shortcomings of recent techniques for muscle proteome analysis are discussed. Data from differential proteomics applied to healthy individuals in normal and unusual environments (hypoxia and cold), in exercise, immobilization, aging and to patients with neuromuscular hereditary disorders (NMDs), inclusion body myositis and insulin resistance are summarized, critically discussed and, when required, compared with homologous data from pertinent animal models. The advantages as well as the limits of proteomics in view of the identification of new biomarkers are evaluate