Development of an online-coupled MARGA upgrade for the 2 h interval quantification of low-molecular-weight organic acids in the gas and particle phases

A method is presented to quantify the lowmolecular- weight organic acids such as formic, acetic, propionic, butyric, pyruvic, glycolic, oxalic, malonic, succinic, malic, glutaric, and methanesulfonic acid in the atmospheric gas and particle phases, based on a combination of the Monitor for AeRosols and Gases in ambient Air (MARGA) and an additional ion chromatography (Compact IC) instrument. Therefore, every second hourly integrated MARGA gas and particle samples were collected and analyzed by the Compact IC, resulting in 12 values per day for each phase. A proper separation of the organic target acids was initially tackled by a laboratory IC optimization study, testing different separation columns, eluent compositions and eluent flow rates for both isocratic and gradient elution. Satisfactory resolution of all compounds was achieved using a gradient system with two coupled anion-exchange separation columns. Online pre-concentration with an enrichment factor of approximately 400 was achieved by solid-phase extraction consisting of a methacrylate-polymer-based sorbent with quaternary ammonium groups. The limits of detection of the method range between 0.5 ngm3 for malonate and 17.4 ngm3 for glutarate. Precisions are below 1.0 %, except for glycolate (2.9 %) and succinate (1.0 %). Comparisons of inorganic anions measured at the TROPOS research site in Melpitz, Germany, by the original MARGA and the additional Compact IC are in agreement with each other (R2 D0.95-0.99). Organic acid concentrations from May 2017 as an example period are presented. Monocarboxylic acids were dominant in the gas phase with mean concentrations of 306 ngm3 for acetic acid, followed by formic (199 ngm3), propionic (83 ngm3), pyruvic (76 ngm3), butyric (34 ngm3) and glycolic acid (32 ngm3). Particulate glycolate, oxalate and methanesulfonate were quantified with mean concentrations of 26, 31 and 30 ngm3, respectively. Elevated concentrations of gas-phase formic acid and particulate oxalate in the late afternoon indicate photochemical formation as a source

Measurements of PM10 ions and trace gases with the online system MARGA at the research station Melpitz in Germany – A five-year study

An hourly quantification of inorganic water-soluble PM10 ions and corresponding trace gases was performed using the Monitor for AeRosols and Gases in ambient Air (MARGA) at the TROPOS research site in Melpitz, Germany. The data availability amounts to over 80% for the five-year measurement period from 2010 to 2014. Comparisons were performed for the evaluation of the MARGA, resulting in coefficients of determinations (slopes) of 0.91 (0.90) for the measurements against the SO2 gas monitor, 0.84 (0.88), 0.79 (1.39), 0.85 (1.20) for the ACSM NO3 −, SO4 2− and NH4 + measurements, respectively, and 0.85 (0.65), 0.88 (0.68), 0.91 (0.83), 0.86 (0.82) for the filter measurements of Cl−, NO3 −, SO4 2− and NH4 +, respectively. A HONO comparison with a batch denuder shows large scatter (R2 = 0.41). The MARGA HNO3 is underestimated compared to a batch and coated denuder with shorter inlets (slopes of 0.16 and 0.08, respectively). Less NH3 was observed in coated denuders for high ambient concentrations. Long-time measurements show clear daily and seasonal variabilities. Potential Source Contribution Function (PSCF) analysis indicates the emission area of particulate ions Cl−, NO3 −, SO4 2−, NH4 +, K+ and gaseous SO2 to lie in eastern European countries, predominantly in wintertime. Coarse mode sea salt particles are transported from the North Sea to Melpitz. The particles at Melpitz are nearly neutralised with a mean molar ratio of 0.90 for the five-year study. A slight increase of the neutralization ratio over the last three years indicates a stronger decrease of the anthropogenically emitted NO3 − and SO4 2− compared to NH4 +

Entwicklung eines zwangläufigen Schneid- und Fixiersystems für den Einsatz in einem Tapelegekopf

Im Rahmen des Bundesxzellenzclusters MERGE EXC 1075 an der TU Chemnitz erfolgte die Entwicklung einer neuartigen großserientauglichen Technologie zur Herstellung faserverstärkter Thermoplastbauteile. Für die Demonstration der Technologie wurde eine Pilotanlage realisiert, die zum Ablegen des Thermoplasttapes über eine Verlegeeinheit – einen sog. Tapelegekopf – verfügt. Mit Abschluss des Legeprozesses wird das Halbzeug, das aus einer angebremsten Spule abgezogen wird, abgeschnitten und der Prozess wird von neuem begonnen. Für das Schneiden des Materials haben Voruntersuchungen gezeigt, dass konturierte Klingen erforderlich sind, um ein Verlaufen des Bandes zu vermeiden. Darüber hinaus hat sich als zweckmäßig erwiesen eine zusätzliche Fixierung vorzunehmen. Dies verbessert die Schnittqualität und Zuverlässigkeit des Systems. Aufgrund enger Bauraumrestriktionen wurde entschieden die Schneidbewegung und das Fixieren zwangläufig synchronisiert auf einen Antrieb zurück zu führen. Hierfür wurden zwei ungleichmäßige Rastgetriebe synthetisiert, ausgelegt sowie in weiteren Entwicklungsstufen auskonstruiert, gefertigt und getestet. Mit der Inbetriebnahme des Gesamtanlagensystems erfolgte ebenfalls der Funktionsnachweis dieses mechanisch zwangläufigen Schneidsystems, das im Rahmen des Vortrags vorgestellt wird. Diese Arbeiten entstanden im Rahmen des Bundesexzellenzclusters EXC 1075 „Technologiefusion für multifunktionale Leichtbaustrukturen“ und wurde von der Deutschen Forschungsgemeinschaft gefördert. Die Autoren danken für die finanzielle Unterstützung

Development of an online-coupled MARGA upgrade for the 2 h interval quantification of low-molecular-weight organic acids in the gas and particle phases

A method is presented to quantify the low-molecular-weight organic acids such as formic, acetic, propionic, butyric, pyruvic, glycolic, oxalic, malonic, succinic, malic, glutaric, and methanesulfonic acid in the atmospheric gas and particle phases, based on a combination of the Monitor for AeRosols and Gases in ambient Air (MARGA) and an additional ion chromatography (Compact IC) instrument. Therefore, every second hourly integrated MARGA gas and particle samples were collected and analyzed by the Compact IC, resulting in 12 values per day for each phase. A proper separation of the organic target acids was initially tackled by a laboratory IC optimization study, testing different separation columns, eluent compositions and eluent flow rates for both isocratic and gradient elution. Satisfactory resolution of all compounds was achieved using a gradient system with two coupled anion-exchange separation columns. Online pre-concentration with an enrichment factor of approximately 400 was achieved by solid-phase extraction consisting of a methacrylate-polymer-based sorbent with quaternary ammonium groups. The limits of detection of the method range between 0.5&thinsp;ng&thinsp;m−3 for malonate and 17.4&thinsp;ng&thinsp;m−3 for glutarate. Precisions are below 1.0&thinsp;%, except for glycolate (2.9&thinsp;%) and succinate (1.0&thinsp;%). Comparisons of inorganic anions measured at the TROPOS research site in Melpitz, Germany, by the original MARGA and the additional Compact IC are in agreement with each other (R2&thinsp;=&thinsp;0.95–0.99). Organic acid concentrations from May 2017 as an example period are presented. Monocarboxylic acids were dominant in the gas phase with mean concentrations of 306&thinsp;ng&thinsp;m−3 for acetic acid, followed by formic (199&thinsp;ng&thinsp;m−3), propionic (83&thinsp;ng&thinsp;m−3), pyruvic (76&thinsp;ng&thinsp;m−3), butyric (34&thinsp;ng&thinsp;m−3) and glycolic acid (32&thinsp;ng&thinsp;m−3). Particulate glycolate, oxalate and methanesulfonate were quantified with mean concentrations of 26, 31 and 30&thinsp;ng&thinsp;m−3, respectively. Elevated concentrations of gas-phase formic acid and particulate oxalate in the late afternoon indicate photochemical formation as a source.</p

Integrated North Sea grids: The costs, the benefits and their distribution between countries

A large number of offshore wind farms and interconnectors are expected to be constructed in the North Sea region over the coming decades, creating substantial opportunities for the deployment of integrated network solutions. Creating interconnected offshore grids that combine cross-border links and connections of offshore plants to shore offers multiple economic and environmental advantages for Europe's energy system. However, despite evidence that integrated solutions can be more beneficial than traditional radial connection practices, no such projects have been deployed yet. In this paper we quantify costs and benefits of integrated projects and investigate to which extent the cost-benefit sharing mechanism between participating countries can impede or encourage the development of integrated projects. Three concrete interconnection case studies in the North Sea area are analysed in detail using a national-level power system model. Model outputs are used to compute the net benefit of all involved stakeholders under different allocation schemes. Given the asymmetric distribution of costs and benefits, we recommend to consistently apply the Positive Net Benefit Differential mechanism as a starting point for negotiations on the financial closure of investments in integrated offshore infrastructure

Treatment of Human Epidermal Growth Factor Receptor 2-Overexpressing Breast Cancer Xenografts With Multiagent HER-Targeted Therapy

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Transphosphorylation of kinase-dead HER3 and breast cancer progression: a new standpoint or an old concept revisited?

Although neither kinase-dead human epidermal growth factor receptor (HER)3 nor orphan HER2 can be activated by HER-related ligands on their own, the formation of HER2/HER3 heterodimers creates the most mitogenic and transforming receptor complex within the HER (erbB) family of transmembrane receptor tyrosine kinases. The incorporation of markers such as HER3 transactivation, HER2/HER3 dimer, or others that may provide information regarding the level of HER pathway engagement has been demonstrated to allow identification of patients who respond to or escape HER-targeted therapies. Pioneering studies showed that high expression of kinase-dead HER3 can predict early escape from the anti-HER2 monoclonal antibody trastuzumab. Also, the growth-inhibitory effects of HER1/2 tyrosine kinase inhibitors (TKIs) were previously found to be attenuated in the presence of heregulin, which is a high-affinity combinatorial ligand for HER3. All of these concepts are being revisited with respect to the efficacy of HER family TKI therapies; in particular, HER3 signalling buffered against incomplete inhibition of HER2 kinase activity has been suggested to be the mechanism that allows HER2 over-expressing breast cancer cells to escape HER TKIs. It remains to be elucidated whether reactivation of HER3 signalling can also account for the poor efficacy of HER TKIs in treating breast carcinomas that contain low overall levels of HER2 receptors. However, it appears that regardless of the mechanism that triggers the formation of oncogenic HER2/HER3 heterodimers (HER2 over-expression or overall low HER2 but high levels of the HER3 ligand heregulin), HER3 transphosphorylation is a common response of breast cancer cells upon treatment with current inhibitors of the HER receptor tyrosine kinase network. Because kinase-inactive HER3 is not presently an amenable target for forthcoming HER TKIs, molecular approaches that can efficiently block heregulin-triggered HER3 transactivation or nucleocytoplasmic trafficking of heregulin might offer novel strategies with which to manage HER-driven breast cancer disease

Mechanism of resistance to trastuzumab and molecular sensitization via ADCC activation by exogenous expression of HER2-extracellular domain in human cancer cells

Trastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic efficacy against HER2-positive breast and gastric cancers; however, acquired resistance presents a formidable obstacle to long-term tumor responses in the majority of patients. Here, we show the mechanism of resistance to trastuzumab in HER2-positive human cancer cells and explore the molecular sensitization by exogenous expression of HER2-extracellular domain (ECD) in HER2-negative or trastuzumab-resistant human cancer cells. We found that long-term exposure to trastuzumab induced resistance in HER2-positive cancer cells; HER2 expression was downregulated, and antibody-dependent cellular cytotoxicity (ADCC) activity was impaired. We next examined the hypothesis that trastuzumab-resistant cells could be re-sensitized by the transfer of non-functional HER2-ECD. Exogenous HER2-ECD expression induced by the stable transfection of a plasmid vector or infection with a replication-deficient adenovirus vector had no apparent effect on the signaling pathway, but strongly enhanced ADCC activity in low HER2-expressing or trastuzumab-resistant human cancer cells. Our data indicate that restoration of HER2-ECD expression sensitizes HER2-negative or HER2-downregulated human cancer cells to trastuzumab-mediated ADCC, an outcome that has important implications for the treatment of human cancers

A double-blind, randomized, multicenter, Italian study of frovatriptan versus almotriptan for the acute treatment of migraine

The objective of this study was to evaluate patients’ satisfaction with acute treatment of migraine with frovatriptan or almotriptan by preference questionnaire. One hundred and thirty three subjects with a history of migraine with or without aura (IHS 2004 criteria), with at least one migraine attack in the preceding 6 months, were enrolled and randomized to frovatriptan 2.5 mg or almotriptan 12.5 mg, treating 1–3 attacks. The study had a multicenter, randomized, double blind, cross-over design, with treatment periods lasting <3 months. At study end patients assigned preference to one of the treatments using a questionnaire with a score from 0 to 5 (primary endpoint). Secondary endpoints were pain free and pain relief episodes at 2 and 4 h, and recurrent and sustained pain free episodes within 48 h. Of the 133 patients (86%, intention-to-treat population) 114 of them expressed a preference for a triptan. The average preference score was not significantly different between frovatriptan (3.1 ± 1.3) and almotriptan (3.4 ± 1.3). The rates of pain free (30% frovatriptan vs. 32% almotriptan) and pain relief (54% vs. 56%) episodes at 2 h did not significantly differ between treatments. This was the case also at 4 h (pain free: 56% vs. 59%; pain relief: 75% vs. 72%). Recurrent episodes were significantly (P < 0.05) less frequent under frovatriptan (30% vs. 44%), also for the attacks treated within 30 min. No significant differences were observed in sustained pain free episodes (21% vs. 18%). The tolerability profile was similar between the two drugs. In conclusion, our study suggests that frovatriptan has a similar efficacy of almotriptan in the short-term, while some advantages are observed during long-term treatment