A C3(H20) recycling pathway is a component of the intracellular complement system

An intracellular complement system (ICS) has recently been described in immune and nonimmune human cells. This system can be activated in a convertase-independent manner from intracellular stores of the complement component C3. The source of these stores has not been rigorously investigated. In the present study, Western blotting identified a band corresponding to C3 in freshly isolated human peripheral blood cells that was absent in corresponding cell lines. One difference between native cells and cell lines was the time absent from a fluid-phase complement source; therefore, we hypothesized that loading C3 from plasma was a route of establishing intracellular C3 stores. We found that many types of human cells specifically internalized C3(H(2)O), the hydrolytic product of C3, and not native C3, from the extracellular milieu. Uptake was rapid, saturable, and sensitive to competition with unlabeled C3(H(2)O), indicating a specific mechanism of loading. Under steady-state conditions, approximately 80% of incorporated C3(H(2)O) was returned to the extracellular space. These studies identify an ICS recycling pathway for C3(H(2)O). The loaded C3(H(2)O) represents a source of C3a, and its uptake altered the cytokine profile of activated CD4(+) T cells. Importantly, these results indicate that the impact of soluble plasma factors should be considered when performing in vitro studies assessing cellular immune function

C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation

Complement C1q is the activator of the classical pathway. However, it is now recognized that C1q can exert functions unrelated to complement activation. Here we show that C1q, but not C4, is expressed in the stroma and vascular endothelium of several human malignant tumours. Compared with wild-type (WT) or C3- or C5-deficient mice, C1q-deficient (C1qa(-/-)) mice bearing a syngeneic B16 melanoma exhibit a slower tumour growth and prolonged survival. This effect is not attributable to differences in the tumour-infiltrating immune cells. Tumours developing in WT mice display early deposition of C1q, higher vascular density and an increase in the number of lung metastases compared with C1qa(-/-) mice. Bone marrow (BM) chimeras between C1qa(-/-) and WT mice identify non-BM-derived cells as the main local source of C1q that can promote cancer cell adhesion, migration and proliferation. Together these findings support a role for locally synthesized C1q in promoting tumour growth

Nonlinear dynamic analysis of gas turbine combustor leaf seal

The leaf seals are one of the typical sealing systems in gas turbine and jet engines. In Baker Hughes LT family gas turbines, they are used to create sealing between the combustion chamber and the first stage nozzle. The leaf seals are thin metallic plates and subjected to dynamic loads and high temperatures. They have curved contacts, and depending on the inclination, they can experience partial contact. Furthermore, when excited by dynamic loads, the leaf seal can be subject to intermittent contact, possibly triggering wear out or vibratory phenomena. Due to its flexibility and its partial seating, it exhibits a complex nonlinear dynamic behaviour, strongly variable with the operating conditions. This study presents a numerical investigation using coupled static/dynamic harmonic balance method (HBM) frequency-based solution technique. The reported solutions include nonlinear forced response and contact studies for various operating and kinematic conditions along with brief insights

Comparison of contact parameters measured with two different friction rigs for nonlinear dynamic analysis

The accurate measurement of contact interface parameters is of great importance for nonlinear dynamic response computations since there is a lack of predictive capabilities for such input parameters. Several test rigs have been developed at different institutions, and a series of measurements published, but their reliability remains unknown due to a lack of direct comparisons. To somehow address this issue, a Round-Robin test campaign was performed including the high frequency friction rigs of Imperial College London and Politecnico di Torino. Comparable hysteresis loops were recorded on specimen pairs manufactured from the same batch of raw stainless steel, for a wide range of test conditions, including varying normal loads, sliding distances and nominal areas of contact. Measurements from the two rigs were compared to quantify the level of agreement between the two very different experimental setup, showing a reasonably good matching in the results, but also highlighting some differences. Results also demonstrated that loading conditions can strongly affect the contact parameters, and consequently their effect must be included in future nonlinear dynamic simulations for more reliable predictions

Liquid drops attract or repel by the inverted Cheerios effect

European Union Grant CIG 618335. S.K. acknowledges financial support from NWO through VIDI Grant 11304. A.P. and J.H.S. acknowledge financial support from European Research Council Consolidator Grant 616918

Fault management in an i.c. engine piezoelectric fuel injection system

A piezoelectric injection system 15, eg for a diesel engine, comprises a VDCpower supply 24 for supplying a power circuit 17 provided with a DC-DC converter having high-side and low-side drivers 20, 21 connected at a switching node 22, the drivers being electrically connected to at least a piezoelectric injector 16. The value of an electric parameter representative of the operation the injection system is monitored and compared with a predetermined reference parameter value, and emergency means 32 are activated when the monitored parameter value exceeds the respective reference value. The electric parameter may be the current flowing through the piezoelectric actuator 19 and/or the low-side driver 21, sensed by current sensor 30, or the voltage across the piezoelectric actuator. The emergency means 32 may interrupt the operation of the drivers 20, 21, discharge the piezoelectric injector or disconnect the injector form the power circuit 1

Model and Design of a Power Driver for Piezoelectric Stack Actuators

A power driver has been developed to control piezoelectric stack actuators used in automotive application. An FEM model of the actuator has been implemented starting from experimental characterization of the stack and mechanical and piezoelectric parameters. Experimental results are reported to show a correct piezoelectric actuator driving method and the possibility to obtain a sensorless positioning control

Serum Amyloid P Aids Complement-Mediated Immunity to Streptococcus pneumoniae

The physiological functions of the acute phase protein serum amyloid P (SAP) component are not well defined, although they are likely to be important, as no natural state of SAP deficiency has been reported. We have investigated the role of SAP for innate immunity to the important human pathogen Streptococcus pneumoniae. Using flow cytometry assays, we show that SAP binds to S. pneumoniae, increases classical pathway–dependent deposition of complement on the bacteria, and improves the efficiency of phagocytosis. As a consequence, in mouse models of infection, mice genetically engineered to be SAP-deficient had an impaired early inflammatory response to S. pneumoniae pneumonia and were unable to control bacterial replication, leading to the rapid development of fatal infection. Complement deposition, phagocytosis, and control of S. pneumoniae pneumonia were all improved by complementation with human SAP. These results demonstrate a novel and physiologically significant role for SAP for complement-mediated immunity against an important bacterial pathogen, and provide further evidence for the importance of the classical complement pathway for innate immunity

Quantitative MRI Measurement of Binder Distributions in Green-State Ceramics

Development of reliable and improved structural ceramics for advanced heat engines and other applications requires process diagnostics and materials evaluation from powder preparation to green-body forming to final sintering. Injection molding is a promising processing method being developed for mass production of complex-shaped heat engine components such as turbochargers (rotors and stator vanes) and engine valves. Major processing steps in injection-molded ceramic manufacturing include preparation of ceramic powders and organic binders, mixing, molding, binder removal, sintering, and finishing [1]. While materials evaluation and diagnostics are needed throughout the process, it is particularly important to evaluate the distributions of binders/plasticizers in as-molded green bodies [2]. Poor distribution of these organics in a green body can lead to a final part that is defective or that has poor mechanical properties after it is sintered