Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'.

Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required

Advances in Understanding Environmental Risks of Red Mud After the Ajka Spill, Hungary

In the 5 years since the 2010 Ajka red mud spill (Hungary), there have been 46 scientific studies assessing the key risks and impacts associated with the largest single release of bauxite-processing residue (red mud) to the environment. These studies have provided insight into the main environmental concerns, as well as the effectiveness of remedial efforts that can inform future management of red mud elsewhere. The key immediate risks after the spill were associated with the highly caustic nature of the red mud slurry and fine particle size, which once desiccated, could generate fugitive dust. Studies on affected populations showed no major hazards identified beyond caustic exposure, while red mud dust risks were considered equal to or lesser than those provided by urban dusts of similar particle size distribution. The longer-term environmental risks were related to the saline nature of the spill material (salinization of inundated soils) and the release and the potential cycling of oxyanion-forming metals and metalloids (e.g., Al, As, Cr, Mo, and V) in the soil–water environment. Of these, those that are soluble at high pH, inefficiently removed from solution during dilution and likely to be exchangeable at ambient pH are of chief concern (e.g., Mo and V). Various ecotoxicological studies have identified negative impacts of red mud-amended soils and sediments at high volumes (typically [5 %) on different test organisms, with some evidence of molecularlevel impacts at high dose (e.g., genotoxic effects on plants and mice). These data provide a valuable database to inform future toxicological studies for red mud. However, extensive management efforts in the aftermath of the spill greatly limited these exposure risks through leachate neutralization and red mud recovery from the affected land. Monitoring of affected soils, stream sediments, waters and aquatic biota (fungi, invertebrates and fish) have all shown a very rapid recovery toward prespill conditions. The accident also prompted research that has also highlighted potential benefits of red mud use for critical raw material recovery (e.g., Ga, Co, V, rare earths, inform), carbon sequestration, biofuel crop production, and use as a soil ameliorant

Candida soluble cell wall β-glucan facilitates ovalbumin-induced allergic airway inflammation in mice: Possible role of antigen-presenting cells

<p>Abstract</p> <p>Background</p> <p>Although fungi have been implicated as initiating/deteriorating factors for allergic asthma, their contributing components have not been fully elucidated. We previously isolated soluble β-glucan from <it>Candida albicans </it>(CSBG) (Ohno et al., 2007). In the present study, the effects of CSBG exposure on airway immunopathology in the presence or absence of other immunogenic allergen was investigated <it>in vivo</it>, and their cellular mechanisms were analyzed both <it>in vivo </it>and <it>in vitro</it>.</p> <p>Methods</p> <p><it>In vivo</it>, ICR mice were divided into 4 experimental groups: vehicle, CSBG (25 μg/animal), ovalbumin (OVA: 2 μg/animal), and CSBG + OVA were repeatedly administered intratracheally. The bronchoalveolar lavage cellular profile, lung histology, levels of cytokines and chemokines in the lung homogenates, the expression pattern of antigen-presenting cell (APC)-related molecules in the lung digests, and serum immunoglobulin values were studied. <it>In vitro</it>, the impacts of CSBG (0–12.5 μg/ml) on the phenotype and function of immune cells such as splenocytes and bone marrow-derived dendritic cells (BMDCs) were evaluated in terms of cell proliferation, the surface expression of APC-related molecules, and OVA-mediated T-cell proliferating activity.</p> <p>Results</p> <p><it>In vivo</it>, repeated pulmonary exposure to CSBG induced neutrophilic airway inflammation in the absence of OVA, and markedly exacerbated OVA-related eosinophilic airway inflammation with mucus metaplasia in mice, which was concomitant with the amplified lung expression of Th2 cytokines and IL-17A and chemokines related to allergic response. Exposure to CSBG plus OVA increased the number of cells bearing MHC class II with or without CD80 in the lung compared to that of others. <it>In vitro</it>, CSBG significantly augmented splenocyte proliferation in the presence or absence of OVA. Further, CSBG increased the expression of APC-related molecules such as CD80, CD86, and DEC205 on BMDCs and amplified OVA-mediated T-cell proliferation through BMDCs.</p> <p>Conclusion</p> <p>CSBG potentiates allergic airway inflammation with maladaptive Th immunity, and this potentiation was associated with the enhanced activation of APCs including DC.</p

Assessing the role of bed sediments in the persistence of red mud pollution in a shallow lake (Kinghorn Loch, UK)

Red mud is a by-product of alumina production. Little is known about the long-term fate of red mud constituents in fresh waters or of the processes regulating recovery of fresh waters following pollution control. In 1983, red mud leachate was diverted away from Kinghorn Loch, UK, after many years of polluting this shallow and monomictic lake. We hypothesised that the redox-sensitive constituents of red mud leachate, phosphorus (P), arsenic (As) and vanadium (V), would persist in the Kinghorn Loch for many years following pollution control as a result of cycling between the lake bed sediment and the overlying water column. To test this hypothesis, we conducted a 12-month field campaign in Kinghorn Loch between May 2012 and April 2013 to quantify the seasonal cycling of P, As, and V in relation to environmental conditions (e.g., dissolved oxygen (DO) concentration, pH, redox chemistry and temperature) in the lake surface and bottom waters. To confirm the mechanisms for P, As and V release, a sediment core incubation experiment was conducted using lake sediment sampled in July 2012, in which DO concentrations were manipulated to create either oxic or anoxic conditions similar to the bed conditions found in the lake. The effects on P, As, and V concentrations and species in the water column were measured daily over an eight-day incubation period. Phosphate (PO4-P) and dissolved As concentrations were significantly higher in the bottom waters (75.9 ± 30.2 μg L−1 and 23.5 ± 1.83 μg L−1, respectively) than in the surface waters (12.9 ± 1.50 μg L−1 and 14.1 ± 2.20 μg L−1, respectively) in Kinghorn Loch. Sediment release of As and P under anoxic conditions was confirmed by the incubation experiment and by the significant negative correlations between DO and P and As concentrations in the bottom waters of the lake. In contrast, the highest dissolved V concentrations occurred in the bottom waters of Kinghorn Loch under oxic conditions (15.0 ± 3.35 μg L−1), with the release from the bed sediment apparently being controlled by a combination of competitive ion concentrations, pH and redox conditions

Metallic modified (bismuth, antimony, tin and combinations thereof) film carbon electrodes.

In this paper in situ bismuth, antimony, tin modified electrodes and combinations thereof are explored towards the model target analytes cadmium(II) and lead(II), chosen since they are the most widely studied, to explore the role of the underlying electrode substrate with respect to boron-doped diamond, glassy carbon, and screen-printed graphite electrodes. It is found that differing electrochemical responses are observed, dependent upon the underlying electrode substrate. The electrochemical response using the available range of metallic modifications is only ever observed when the underlying electrode substrate exhibits relatively slow electron transfer properties; in the case of fast electron transfer properties, no significant advantages are evident. Furthermore these bismuth modified systems which commonly employ a pH 4 acetate buffer, reported to ensure the bismuth(III) stability upon the electrode surface can create create a problem when sensing at low concentrations of heavy metals due to its high background current. It is demonstrated that a simple change of pH can allow the detection of the target analytes (cadmium(II) and lead(II)) at levels below that set by the World Health Organisation (WHO) using bare graphite screen-printed electrodes

Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors

Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is an important human bacterial pathogen that can cause invasive infections. Once it colonizes its exclusively human host, GAS needs to surmount numerous innate immune defense mechanisms, including opsonization by complement and consequent phagocytosis. Several strains of GAS bind to human-specific complement inhibitors, C4b-binding protein (C4BP) and/or Factor H (FH), to curtail complement C3 (a critical opsonin) deposition. This results in diminished activation of phagocytes and clearance of GAS that may lead to the host being unable to limit the infection. Herein we describe the course of GAS infection in three human complement inhibitor transgenic (tg) mouse models that examined each inhibitor (human C4BP or FH) alone, or the two inhibitors together (C4BPxFH or 'double' tg). GAS infection with strains that bound C4BP and FH resulted in enhanced mortality in each of the three transgenic mouse models compared to infection in wild type mice. In addition, GAS manifested increased virulence in C4BPxFH mice: higher organism burdens and greater elevations of pro-inflammatory cytokines and they died earlier than single transgenic or wt controls. The effects of hu-C4BP and hu-FH were specific for GAS strains that bound these inhibitors because strains that did not bind the inhibitors showed reduced virulence in the 'double' tg mice compared to strains that did bind; mortality was also similar in wild-type and C4BPxFH mice infected by non-binding GAS. Our findings emphasize the importance of binding of complement inhibitors to GAS that results in impaired opsonization and phagocytic killing, which translates to enhanced virulence in a humanized whole animal model. This novel hu-C4BPxFH tg model may prove invaluable in studies of GAS pathogenesis and for developing vaccines and therapeutics that rely on human complement activation for efficacy

Demonstracja podejścia "grey-box" do diagnostyki wymiennika wody zasilającej (Część II) - strojenie modelu na podstawie danych operacyjnych

Work related to the first-principle modeling of a boiler feedwater heater operating in a power unit is presented, along with theoretical discussion concerning its structural simplifications, parameter estimation, and dynamical validation. The objectives of this work are as follows: (i) formulate a moderately complex first-principle model of a feedwater heater to reproduce operational measurements in real-time simulations, (ii) develop a tuning method for this model, (iii) propose key indicators of heater performance using a model-based approach, and finally (iv) automate the calculation process of the indicators. The first objective has been addressed in the first paper while the remaining objectives are dealt with in this paper. The paper discusses a nonlinear least-square optimization technique used to adjust the phenomenological parameters of the feedwater heater model, i.e. heat transfer coefficients. The model variables (e.g. variability of the power rate of energy exchange) and estimated parameter values were used to formulate key performance indicators intended for a model-driven diagnostics approach. The computational process was organized in an iterative process of updating model parameters and indicators. The validation was successfully performed using operational data from a 225MW coal-fired power unit.Artykuł przedstawia proces modelowania podgrzewacza regeneracyjnego pracującego w systemie bloku energetycznego z wykorzystaniem równań fizycznych. Artykuł zawiera dyskusje dotycząca uproszczeń struktury modelu, estymacji jego parametrów oraz walidacji. Celami pracy jest: (i) sformułowanie umiarkowanie złożonego modelu wymiennika odtwarzającego dane pomiarowe w rzeczywistej skali czasu, (ii) przedstawienie metody strojenia modelu, (iii) zaproponowanie wskaźników użyteczności podgrzewacza na podstawie podejścia wspartego modelem, oraz (iv) automatyzacja procesu wyznaczania tych wskaźników. Pierwszy z celów zawiera się w pierwszej części pracy, a pozostałe w części drugiej. Artykuł zawiera dyskusję wyników zastosowania nieliniowej metod najmniejszych kwadratów w celu dostrojenia parametrów fenomenologicznych modelu podgrzewacza wody zasilającej, tj. współczynników wymiany ciepła. Zmienne modelu (np. chwilowy transfer energii) oraz wartości estymowanych parametrów zostały użyte w celu sformułowania wskaźników odpowiednich dla diagnostyki bloku energetycznego wspartej modelem. Proces obliczeniowy został zorganizowany w sposób iteracyjnego uaktualniania parametrów modelu oraz wskaźników, na podstawie danych operacyjnych pochodzących z 225 MW bloku opalanego węglem kamiennym

Parametryczne podejście do diagnostyki maszyn wirnikowych w przejściowych warunkach działania

The aim of the paper is to recognize diagnostic symptoms based on parametric modeling with the use of system identification methods in the scope of monitoring techniques intended for rotating machinery. The diagnostic symptoms may prove to be a powerful tool for the decision support systems based on easier interpretable parameters of a parametric model.Celem artykułu jest rozpoznanie symptomów diagnostycznych na podstawie modelowania parametrycznego z wykorzystaniem identyfikacji systemów w zakresie technik monitorowania przeznaczonych dla maszyn wirnikowych. Symptomy diagnostyczne mogą okazać się użyteczne dla systemów wspomagania decyzji opartych na łatwo interpretowalnych parametrach modeli parametrycznych

Application of an inverse data-driven model for reconstructing wheel movement signals

This paper considers a method for indirect measuring the vertical displacement of wheels resulting from the road profile, using an inverse parametric data-driven model. Wheel movement is required in variable damping suspension systems, which use an onboard electronic control system that improves ride quality and vehicle handling in typical maneuvres. This paper presents a feasibility study of such an approach which was performed in laboratory conditions. Experimental validation tests were conducted on a setup consisting of a servo-hydraulic test rig equipped with displacement, force and acceleration transducers and a data-acquisition system. The fidelity and adequacy of various parametric SISO model structures were evaluated in the time domain based on correlation coefficient, FPE and AIC criteria. The experimental test results showed that inverse models provide accuracy of inversion, ranging from more than 70% for the ARX model structure to over 90% for the OE model structure