A Numerical Investigation of Potential Ion Current Sensor Applications in Premixed Charge Compression Ignition Engine

Simultaneous reduction of engine pollutants (e.g., CO, THC, NOx, and soot) is one of the main challenges in the development of new combustion systems. Low-temperature combustion (LTC) concepts in compression ignition (CI) engines like premixed charged compression ignition (PCCI) make use of pre-injections to create a partly homogenous mixture. In the PCCI combustion regime, a direct correlation between injection and pollutant formation is no longer present because of long ignition delay times. In LTC combustion systems, the in-cylinder pressure sensor is normally used to help the combustion control. However, to allow the control of PCCI engines, new sensor concepts are investigated to obtain additional information about the PCCI combustion for advanced controller structures. In LTC combustion systems like gasoline-controlled autoignition (GCAI) concepts, the application of ion current sensors enables additional monitoring of the combustion process with real-time capability. In analogy to GCAI, the use of an ion current sensor for the control of PCCI combustion in diesel engines could allow effective pollutant and combustion control. To investigate the potential of the application of an ion current sensor for controlling a PCCI engine, numerical engine investigations have been performed and are presented in this work. Experimental data of a single cylinder engine (SCE) are used to validate a RANS 3D-CFD simulation framework focusing on the prediction of engine-out emissions. The assembled chemical kinetic model accounts for ion and NOx formation inside the combustion chamber. After model validation, operating conditions with varying pre-injection patterns were analyzed to find correlations between pollutant and ion formation. The simulation results show a correlation between NOx and ion formation, suggesting that engine controls relying on ion current measurements potentially allow for a reduction of NOx emissions. Applying ion current sensors to control PCCI combustion seems promising to reduce pollutant emissions and improve the engine's overall performance through real-time in-cycle control strategies.</p

Management of synchronous operations on domain names of the ccTLD .it

This document details the operations needed for registering and maintaining domain names in accordance with synchronous registration. The synchronous system for registering and maintaining a domain name is provided by organizations (henceforth Registrars) that have an active contract with the Registry (henceforth .it Registry or Registry of the ccTLD.it), which is subordinate to an accreditation procedure. The Registrar will always be an intermediary with the Registry for all domain name registering and maintenance and also for correctly updating the Database of Assigned Names (DBNA) by using the synchronous registration system. The synchronous registration system allows Registrars to register and maintain domain names in realtime within the limits set out in the "Rules for assigning and managing domain names in the ccTLD.it" (hereafter, "Rules"). The synchronous system for registering and maintaining domain names of the .it Registry uses the protocol EPP (Extensible Provisioning Protocol) to comply with internationally accepted standards and to comply with decisions already made by other ccTLDs and gTLDs. EPP is a synchronous client-server protocol based on XML

Cytokine dysregulation despite immunoglobulin replacement therapy in common variable immunodeficiency (CVID)

IntroductionCommon variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency. CVID is a heterogeneous disorder with a presumed multifactorial etiology. Intravenous or subcutaneous immunoglobulin replacement therapy (IgRT) can prevent severe infections but not underlying immune dysregulation.MethodsIn this study, we evaluated the serum concentrations of proinflammatory (TNF-α, IL-1β, IL-6) and immunoregulatory cytokines (IL-10), as well as lipopolysaccharide (LPS) and soluble CD14 (sCD14) in CVID individuals with infectious only (INF-CVID), and those with additional systemic autoimmune and inflammatory disorders (NIC-CVID), and healthy donors (HD).ResultsOur results showed increased serum concentrations of TNF-α, IL-1β, IL-6, and IL-10 in both INF-CVID and NIC-CVID subjects compared to HD. However, elevations of TNF-α, IL-1β, IL-6, and IL-10 were significantly more marked in NIC-CVID than INF-CVID. Additionally, LPS concentrations were increased only in NIC-CVID but not in INF-CVID compared to HD. Circulating levels of sCD14 were significantly increased in NIC-CVID compared to both INF-CVID and HD.DiscussionThese findings indicate persistent cytokine dysregulation despite IgRT in individuals with CVID. Moreover, the circulating cytokine profile reveals the heterogeneity of immune dysregulation in different subgroups of CVID subjects

Neurologic and Psychiatric Manifestations of Bradykinin-Mediated Angioedema: Old and New Challenges

Neurologic manifestations have been occasionally described in patients with bradykinin-mediated angioedema. The existing literature is currently limited to case series and case reports mainly described in the hereditary forms (HAE) concerning central nervous system (CNS) involvement. On the contrary, very little is known about peripheral and autonomic nervous system manifestations. CNS involvement in HAE may present with symptoms including severe headaches, visual disturbance, seizures, and various focal and generalized deficits. In addition, a stroke-like clinical picture may present in HAE patients. In turn, some drugs used in patients with cardiovascular and neurologic disorders, such as recombinant tissue plasminogen activator (r-tPA) and angiotensin-converting enzyme inhibitors (ACEI), may produce medication-induced angioedema, resulting in a diagnostic challenge. Finally, most patients with HAE have higher levels of psychological distress, anxiety, and depression. With this review, we aimed to provide an organized and detailed analysis of the existing literature on neurologic and psychiatric manifestations of HAE to shed light on these potentially invalidating symptoms and lay the foundation for further personalized diagnostic pathways for patients affected by this protean disease

Size-Based Effects of Anthropogenic Ultrafine Particles on Lysosomal TRPML1 Channel and Autophagy in Motoneuron-like Cells

An emerging body of evidence indicates an association between anthropogenic particulate matter (PM) and neurodegeneration. Although the historical focus of PM toxicity has been on the cardiopulmonary system, ultrafine PM particles can also exert detrimental effects in the brain. However, only a few studies are available on the harmful interaction between PM and CNS and on the putative pathomechanisms

Group V Secreted Phospholipase A2 Induces the Release of Proangiogenic and Antiangiogenic Factors by Human Neutrophils

Secreted phospholipases A2 (sPLA2s) are extracellular enzymes that catalyze the release of free fatty acids and lysophospholipids from membrane phospholipids and also bind to different receptors (e.g., PLA2R1 or integrins). To date, 12 mammalian sPLA2s have been identified, which play a critical role in pathophysiological processes including inflammation and cancer. sPLA2s activate immune cells such as human neutrophils (PMNs) by enzymatic activity- or receptor-mediated mechanisms. In addition, human PMNs synthesize and store human group V (hGV) and human group X (hGX) sPLA2s in their granules, but only the former is released upon cellular activation. We investigated the effects of sPLA2s on the release of proangiogenic and antiangiogenic factors by PMNs. We found that exogenous hGV and hGX sPLA2s induce the release of vascular endothelial growth factor (VEGF)-A, angiopoietin 1 (Ang1), and CXCL8/IL-8. Only hGV induces the secretion of the antiangiogenic isoform of VEGF-A, namely, VEGF-A165b. While the release of VEGF-A, Ang1, and CXCL8/IL-8 was likely mediated by hGV enzymatic activity and/or binding to PLA2R1 and heparan sulfate proteoglycans, the release of VEGF-A165b requires the interaction with αVβ3 and α4β1 integrins. We also provide evidence that endogenous hGV released by N-formyl-met-leu-phe (fMLF)-activated PMNs is involved in the release of angiogenic factors. The translational relevance of these data is supported by our findings that hGV expression is increased in human samples of lung cancer which are infiltrated by PMNs. Overall, our results suggest that the hGV-neutrophil axis may play a relevant role in the modulation of cancer-related inflammation and angiogenesis

hereditary angioedema attack what happens to vasoactive mediators

Abstract Hereditary angioedema is a disabling, life-threatening condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein (C1-INH-HAE) leading to bradykinin accumulation and recurrent episodes of edema attack. Vascular leakage is a complex process sustained by the coordinated production of several permeabilizing factors including vascular endothelial growth factors (VEGFs), angiopoietins (ANGPTs) and phospholipase A2 enzymes (PLA2). We previously reported that patients with C1-INH-HAE in remission have increased plasma levels of VEGFs, ANGPTs and secreted PLA2. In this study, we sought to analyze plasma levels of these mediators in 15 patients with C1-INH-HAE during the acute attack compared to remission. Plasma concentrations of VEGF-A, VEGF-C and VEGF-D were not altered during attack compared to remission. Moreover, VEGF-D concentrations were not altered also in remission phase compared to controls. Concentrations of ANGPT1, a vascular stabilizer, were increased during attacks compared to symptoms-free periods, whereas ANGPT2 levels were not altered. The ANGPT2/ANGPT1 ratio was decreased during angioedema attacks. Platelet activating factor acetylhydrolase activity was increased in patients with C1-INH-HAE in remission compared to controls and was decreased during angioedema attacks. Our results emphasize the complexity by which several vasoactive mediators are involved not only in the pathophysiology of C1-INH-HAE, but also during angioedema attacks and its resolution