Measurement-Based Modal Beamforming Using Planar Circular Microphone Arrays

This paper describes how to use a planar circular pressure-zone table-top microphone array for modal beamforming. Its goals are similar as for spherical arrays: higher-order resolution and a more-or-less steering-invariant beampattern design in the three-dimensional half space. As conventional circular arrays lack control of the beampattern in the vertical array plane, the proposed arrangement tries to fix this shortcoming to allow both horizontal and vertical control of beamforming. To provide a fully calibrated decomposition into the directional modes, the proposed beamforming approach is based on measurement data. From a MIMO (multiple-input-multiple-output) system description of the measurement data in the spherical harmonics domain, an inverse MIMO system of filters is designed for decomposing the microphone array signals into those spherical components eligible for modal beamforming. For an efficient measurement and robust set of decomposition filters, a reduced set of measurement positions and a regularisation strategy is suggested

Damage Mechanisms and Anisotropy of an AA7010-T7452 Open-Die Forged Alloy: Fatigue Crack Propagation

The process–microstructure–property relationship of high-strength 7000 series aluminum alloys during fatigue crack propagation (FCP) is highly relevant for safety during the design and service of aircraft structural components. It is scientifically evident that many metallurgical factors affect FCP properties, but partly contradictory or inconclusive results show that the quantitative description of the relationships is still a major challenge among researchers and engineers. Most research focuses on sheet or plate products and investigations lack quantitative information on the process–property relationship between open-die forged thick products and FCP. The present study contributes to this field by investigating the fatigue crack growth behavior of an open-die forged AA7010-T7452 aluminum alloy. Four different forging conditions comprising different characteristic microstructures are comparatively analyzed. The influence of grain size, grain shape, specimen orientation, crystallographic texture, and primary phase particles is investigated. Fractographic analysis reveals different active damage mechanisms during fatigue crack growth. Based on that, the microstructure features relevant to fatigue damage areidentified in each regime of crack growth

The Alkamide trans-Pellitorine Targets PPARγ via TRPV1 and TRPA1 to Reduce Lipid Accumulation in Developing 3T3-L1 Adipocytes

Adipose tissue is an important endocrine organ in the human body. However, pathological overgrowth is associated with chronic illness. Regulation of adipogenesis and maturation of adipocytes via bioactive compounds in our daily diet has been in focus of research in the past years and showed promising results for agonists of the ion channels transient receptor potential channel (TRP) V1 and A1. Here, we investigated the anti-adipogenic potential and underlying mechanisms of the alkamide trans-pellitorine present in Piper nigrum via TRPV1 and TRPA1 in 3T3-L1 cells. trans-pellitorine was found to suppress mean lipid accumulation, when applied during differentiation and maturation, but also during maturation phase solely of 3T3-L1 cells in a concentration range between 1 nM and 1 μM by up to 8.84 ± 4.97 or 7.49 ± 5.08%, respectively. Blockage of TRPV1 using the specific inhibitor trans-tert-butyl-cyclohexanol demonstrated that the anti-adipogenic activity of trans-pellitorine depends on TRPV1. In addition, blockage of the TRPA1 channel using the antagonist AP-18 showed a TRPA1-dependent signaling in the early to intermediate stages of adipogenesis. On a mechanistic level, treatment with trans-pellitorine during adipogenesis led to reduced PPARγ expression on gene and protein level via activation of TRPV1 and TRPA1, and increased expression of the microRNA mmu-let-7b, which has been associated with reduced PPARγ levels. In addition, cells treated with trans-pellitorine showed decreased expression of the gene encoding for fatty acid synthase, increased expression of microRNA-103 and a decreased short-term fatty acid uptake on the functional level. In summary, these data point to an involvement of the TRPV1 and TRPA1 cation channels in the anti-adipogenic activity of trans-pellitorine via microRNA-let7b and PPARγ. Since trans-pellitorine does not directly activate TRPV1 or TRPA1, an indirect modulation of the channel activity is assumed and warrants further investigation

Synphilin-1 Enhances α-Synuclein Aggregation in Yeast and Contributes to Cellular Stress and Cell Death in a Sir2-Dependent Manner

© 2010 Büttner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Parkinson’s disease is characterized by the presence of cytoplasmic inclusions, known as Lewy bodies, containing both aggregated α-synuclein and its interaction partner, synphilin-1. While synphilin-1 is known to accelerate inclusion formation by α-synuclein in mammalian cells, its effect on cytotoxicity remains elusive. Methodology/Principal Findings: We expressed wild-type synphilin-1 or its R621C mutant either alone or in combination with α-synuclein in the yeast Saccharomyces cerevisiae and monitored the intracellular localization and inclusion formation of the proteins as well as the repercussions on growth, oxidative stress and cell death. We found that wild-type and mutant synphilin-1 formed inclusions and accelerated inclusion formation by α-synuclein in yeast cells, the latter being correlated to enhanced phosphorylation of serine-129. Synphilin-1 inclusions co-localized with lipid droplets and endomembranes. Consistently, we found that wild-type and mutant synphilin-1 interacts with detergent-resistant membrane domains, known as lipid rafts. The expression of synphilin-1 did not incite a marked growth defect in exponential cultures, which is likely due to the formation of aggresomes and the retrograde transport of inclusions from the daughter cells back to the mother cells. However, when the cultures approached stationary phase and during subsequent ageing of the yeast cells, both wild-type and mutant synphilin-1 reduced survival and triggered apoptotic and necrotic cell death, albeit to a different extent. Most interestingly, synphilin-1 did not trigger cytotoxicity in ageing cells lacking the sirtuin Sir2. This indicates that the expression of synphilin-1 in wild-type cells causes the deregulation of Sir2-dependent processes, such as the maintenance of the autophagic flux in response to nutrient starvation. Conclusions/Significance: Our findings demonstrate that wild-type and mutant synphilin-1 are lipid raft interacting proteins that form inclusions and accelerate inclusion formation of α-synuclein when expressed in yeast. Synphilin-1 thereby induces cytotoxicity, an effect most pronounced for the wild-type protein and mediated via Sir2-dependent processes.This work was supported by grants from IWT-Vlaanderen (SBO NEURO-TARGET), the K.U.Leuven Research Fund (K.U.Leuven BOF-IOF) and K.U.Leuven R&D to JW, a Tournesol grant from Egide (Partenariat Hubert Curien) in France in collaboration with the Flemish Ministry of Education and the Fund of Scientific Research of Flanders (FWO) in Belgium to JW, MCG and LB, a shared PhD fellowship of the EU-Marie Curie PhD Graduate School NEURAD to JW, MCG and LB, grants of the Austrian Science Fund FWF (Austria) to FM and DR (S-9304-B05), to FM and SB (LIPOTOX), and to SB (T-414-B09; Hertha-Firnberg Fellowship) and an EMBO Installation Grant, a Marie Curie IRG, and a grant of the Fundação para a Ciência e Tecnologia (PTDC/SAU-NEU/105215/2008) to TFO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study

Background: Sepsis and severe focal infections represent a substantial disease burden in children admitted to hospital. We aimed to understand the burden of disease and outcomes in children with life-threatening bacterial infections in Europe. Methods: The European Union Childhood Life-threatening Infectious Disease Study (EUCLIDS) was a prospective, multicentre, cohort study done in six countries in Europe. Patients aged 1 month to 18 years with sepsis (or suspected sepsis) or severe focal infections, admitted to 98 participating hospitals in the UK, Austria, Germany, Lithuania, Spain, and the Netherlands were prospectively recruited between July 1, 2012, and Dec 31, 2015. To assess disease burden and outcomes, we collected demographic and clinical data using a secured web-based platform and obtained microbiological data using locally available clinical diagnostic procedures. Findings: 2844 patients were recruited and included in the analysis. 1512 (53·2%) of 2841 patients were male and median age was 39·1 months (IQR 12·4–93·9). 1229 (43·2%) patients had sepsis and 1615 (56·8%) had severe focal infections. Patients diagnosed with sepsis had a median age of 27·6 months (IQR 9·0–80·2), whereas those diagnosed with severe focal infections had a median age of 46·5 months (15·8–100·4; p<0·0001). Of 2844 patients in the entire cohort, the main clinical syndromes were pneumonia (511 [18·0%] patients), CNS infection (469 [16·5%]), and skin and soft tissue infection (247 [8·7%]). The causal microorganism was identified in 1359 (47·8%) children, with the most prevalent ones being Neisseria meningitidis (in 259 [9·1%] patients), followed by Staphylococcus aureus (in 222 [7·8%]), Streptococcus pneumoniae (in 219 [7·7%]), and group A streptococcus (in 162 [5·7%]). 1070 (37·6%) patients required admission to a paediatric intensive care unit. Of 2469 patients with outcome data, 57 (2·2%) deaths occurred: seven were in patients with severe focal infections and 50 in those with sepsis. Interpretation: Mortality in children admitted to hospital for sepsis or severe focal infections is low in Europe. The disease burden is mainly in children younger than 5 years and is largely due to vaccine-preventable meningococcal and pneumococcal infections. Despite the availability and application of clinical procedures for microbiological diagnosis, the causative organism remained unidentified in approximately 50% of patients

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Einfluss von Alkamiden auf Mechanismen der Freisetzung von Serotonin und Dopamin in SH-SY5Y Zellen

Übergewicht stellt ein globales Problem dar und ist unter anderem auf eine zu hohe Energieaufnahme zurückzuführen. Capsaicin erhöht kalziumabhängig durch Aktivierung des TRPV1-Rezeptors die Ausschüttung der Neurotransmitter Serotonin und Dopamin. Eine Stimulierung dieser Neurotransmitter bewirkt eine Reduktion der Nahrungsaufnahme, was eine Gewichtsabnahme zur Folge hat. Im Rahmen dieser Arbeit wurden die neurotransmitterstimulierenden Effekte von Capsaicin in vitro in neuronalen SH-SY5Y Zellen bestätigt und eine weniger scharfe und strukturell ähnliche Substanz mit vergleichbaren Effekten gesucht. Alkamide wurden getestet, das potenteste Alkamid hinsichtlich der Neurotransmitterausschüttung mit Capsaicin verglichen und der Einfluss auf die Genregulation ausgewählter Serotonin- und Dopaminrezeptoren und möglicher Bindungsrezeptoren untersucht. 1 µM Capsaicin führte zu einer maximalen Erhöhung der Serotoninausschüttung um 73 ± 51 % und 10 µM zu einer maximalen Steigerung der Dopaminausschüttung um 1196 ± 535 %. 0,1 µM trans-Pellitorin, das potenteste Alkamid, führte zur größten Erhöhung der Serotoninfreisetzung um 40 ± 26 % und zur Erhöhung der Dopaminfreisetzung um 83 ± 55 %. Die Effekte von 0,1 µM trans-Pellitorin hinsichtlich der Ausschüttung von Serotonin (140 ± 26 %) und Dopamin (183 ± 55 %) waren vergleichbar mit denen von Capsaicin (112 ± 22 % bzw. 221 ± 35 %). 0,1 µM trans-Pellitorin führte zu einer zeitabhängigen Regulation der Serotoninrezeptoren 5-HT2A, 5-HT1A, 5-HT1B und der Dopaminrezeptoren D1 und D2. Außerdem führte 0,1 µM trans-Pellitorin zu einer Erhöhung der Expression des TRPA1-Rezeptors und zu einer Verminderung des CNR1-Rezeptors. Trans-Pellitorin führte, möglicherweise kalziumabhängig über Aktivierung des TRPA1-Rezeptors, zu einer vermehrten Freisetzung der Neurotransmitter Serotonin und Dopamin in neuronalen SH-SY5Y Zellen.Overweight is a worldwide problem, which is, among others, a result of an overconsumption of energy. Capsaicin increases, Ca2+-dependently via activation of the TRPV1-receptor, the release of the neurotransmitters serotonin and dopamine. A stimulation of these neurotransmitters is associated with reduced food intake, resulting in weight loss. This thesis aimed to confirm the neurotransmitter-stimulating effect of capsaicin in vitro in neuronal SH-SY5Y cells and to identify a less pungent structural related compound with comparable effects. Natural alkamides were screened and the most effective compound was compared to capsaicin. Also the effect on serotonin and dopamine receptor gene expression and the impact on possible target receptors were studied. 1 µM Capsaicin most potently increased the release of serotonin by 73 ± 51 % and 10 µM the release of dopamine by 1196 ± 535 %. 0.1 µM trans-pellitorine, the most effective alkamide, increased the release of serotonin by 40 ± 26 % and the release of dopamine by 83 ± 55 %. The effects of 0.1 µM trans-pellitorine on serotonin (140 ± 26 %) and dopamine (183 ± 55 %) release were comparable to capsaicin (112 ± 22 % or 221 ± 35 %). 0.1 µM trans-pellitorine led to a time-dependent regulation of the serotonin receptors 5-HT2A, 5-HT1A, 5-HT1B and dopamine receptors D1 und D2. 0.1 µM trans-pellitorine increased the expression of TRPA1 mRNA and reduced those of CNR1 mRNA. Trans-pellitorine increased, possibly via a TRPA1-mediated, Ca2+-dependent mechanism, the release of the neurotransmitter serotonin and dopamine in neuronal SH-SY5Y cells