559 research outputs found

    Two Price Regimes in Limit Order Books: Liquidity Cushion and Fragmented Distant Field

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    The distribution of liquidity within the limit order book is essential for the impact of market orders on the stock price and the emergence of price shocks. Hence it is of great interest to improve the understanding of the time-dependent dynamics of the limit order book. In our analysis we find a broad distribution of limit order lifetimes. Around the quotes we find a densely filled regime with mostly short living limit orders, far away from the quotes we find a sparse filling with mostly long living limit orders. We determine the characteristics of those two regimes and point out the main differences. Based on our research we propose a model for simulating the regime around the quotes

    Detektion neuroaktiver Substanzen durch Modifikation des AktivitÀtsmusters neokortikaler Netzwerke auf Multielektrodenarrays - Charakterisierung und Optimierung eines neuronalen Biosensors

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    In dieser Arbeit wurden kortikale neuronale Netzwerke auf Multielektrodenarrays auf ihre Tauglichkeit als zellbasiertes Biosensorsystem untersucht. Der Schwerpunkt der pharmakologischen Untersuchungen an den ausgereiften kortikalen Netzwerken lag auf dem Einsatz von Substanzen, welche auf den GABAA-Rezeptor einwirken. Die Modifikation des spontan generierten AktivitĂ€tsmusters ließ dabei RĂŒckschlĂŒsse auf die Wirksamkeit und den Wirkungsmechanismus der Testsubstanzen zu. Ferner war in den meisten FĂ€llen eine Diskriminierung der auf den gleichen Rezeptor einwirkenden Substanzen möglich. Die Analyse der Spikerate und verschiedener auf Bursts beruhender Messparameter machte deutlich, dass die Burstrate bei den extrazellulĂ€ren Ableitungen auf Netzwerkebene den sensitivsten und verlĂ€sslichsten Parameter zum Nachweis der Substanzeffekte darstellte. Durch die Verwendung kortikaler Netzwerke unter optimierten Kulturbedingungen und einer auf das System abgestimmten Analysesoftware konnte die Reproduzierbarkeit und SensitivitĂ€t im Vergleich zu anderen Studien deutlich verbessert werden. Um die extrazellulĂ€re Signalableitung von einer möglichst geringen Zellanzahl und damit einem ĂŒberschaubaren zellulĂ€ren Netzwerk auf Multielektrodenarrays zu ermöglichen, wurden die OberflĂ€cheneigenschaften der Substrate so modifiziert, dass die Lokalisation der Zellsomata und das Auswachsen der Neurite einer geometrischen Kontrolle unterlag. Die kontrollierte Substratbeschichtung des AdhĂ€sionspromotors Poly-D-Lysin in einem triangulĂ€ren Muster konnte dabei durch die Methode des Mikrokontaktstempelns realisiert werden. Durch das kontrollierte Zellwachstum konnte die extrazellulĂ€re Ableitung von Netzwerken einer geringen Zelldichte ĂŒber einen Zeitraum von mehreren Wochen ermöglicht werden. Die Untersuchung struktureller und morphogenetischer Eigenschaften, sowie elektrophysiologische Untersuchungen der strukturierten Netzwerke bewiesen, dass die kontrollierte Substratbeschichtung sich nicht negativ auf das Wachstum, die Synaptogenese und die FunktionalitĂ€t auswirkte.Neocortical networks cultured on microelectrode arrays (MEAs) offer a robust system for biosensor application by using extracellular multi-unit recording of action potentials and analyzing the electrophysiological effects of neuroactive substances. Electrical activity was quantified by a set of parameters extracted from the network activity profile. A neuroactive agent characteristically modifies these parameters, allowing for analytical as well as functional conclusions, i.e. information about the presence, dose, and mode of action of the test substance. Several parameters were analyzed and it was shown that the burstrate is the most sensitive and reliable. By analyzing the spontaneous activity of the cortical cultures with an optimized software set, reproducibility and sensitivity of the system were significantly enhanced in comparison to other investigations. For further characterization of neuronal activity, networks of limited density and complexity are required. But in low density cultures, the cellular arrangement often performs a poor fit to the electrode positions, which results in the recording of merely a small fraction of cells. To overcome this shortcoming, surface characteristics of the MEAs were modified to promote cell adhesion and growth. The microcontact printing method was used to apply the adhesion promoter poly-D-lysine in a two-dimensional, triangular pattern on the MEA surface. Controlled cell growth, allowed the successful extracellular signal recording of low density networks for several weeks. Morphological and physiological properties of these patterned networks kept up with those of unpatterned cultures, thus offering a promising means to characterize neuronal activity in networks of limited complexity via a combination of surface structuring and multi-unit recording

    Electrochemical treatment of a graphitic forging lubricant effluent: The effect of chloride concentration and current density

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    The graphite removal and the chemical oxygen demand (COD) reduction by the electrochemical treatment of an effluent containing a lubricant (oil in water emulsion with graphite) was investigated. The electrochemical cell used a pair of aluminum plates. Since the effluent conductivity was very low, NaCl was used as supporting electrolyte and different current densities as well as different distance between the electrodes were applied. In lower current densities, higher chloride concentrations implied in smaller COD values. The same behavior was observed when electrode distance was decreased. All the tested conditions presented significant graphite removal and COD reductions larger than 94%GKN Driveline Brazil is gratefully acknowledged for all the financial support and material given to the execution of this paper. Also, Capes, FAPERGS, CNPq, and Cyted are thanked for their financial support.Borsa, MB.; Jungblut, R.; PĂ©rez-Herranz, V.; MĂŒller, L.; Moura Bernardes, A.; Bergmann, C. (2016). Electrochemical treatment of a graphitic forging lubricant effluent: The effect of chloride concentration and current density. Separation Science and Technology. 51(1):126-134. doi:10.1080/01496395.2015.1086799S12613451

    Depletion-induced percolation in networks of nanorods

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    Above a certain density threshold, suspensions of rod-like colloidal particles form system-spanning networks. Using Monte Carlo simulations, we investigate how the depletion forces caused by spherical particles affect these networks in isotropic suspensions of rods. Although the depletion forces are strongly anisotropic and favor alignment of the rods, the percolation threshold of the rods decreases significantly. The relative size of the effect increases with the aspect ratio of the rods. The structural changes induced in the suspension by the depletant are characterized in detail and the system is compared to an ideal fluid of freely interpenetrable rods.Comment: 4 pages, 3 figure

    Cell Microbiol.

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    Helicobacter pylori is one of the most common bacterial pathogens, infecting about 50% of the world population. The presence of a pathogenicity island (PAl) in H. pylori has been associated with gastric disease. We present evidence that the H. pylori protein encoded by the cytotoxin- associated gene A (cagA) is translocated and phosphorylated in infected epithelial cells. Two-dimensional gel electrophoresis (2-DE) of proteins isolated from infected AGS cells revealed H. pylori strain-specific and time- dependent tyrosine phosphorylation and dephosphorylation of several 125-135 kDa and 75-80 kDa proteins. Immunoblotting studies, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), cell fractionation and confocal microscopy demonstrated that one of the 125-135 kDa proteins represents the H. pylori CagA protein, which is translocated into the host cell membrane and the cytoplasm. Translocation of CagA was dependent on functional cagA gene and virulence (vir) genes of a type IV secretion apparatus composed of virB4, virB7, virB10, virB11 and virD4 encoded in the cag PAl of H. pylori. Our findings support the view that H. pylori actively translocates virulence determinants, including CagA, which could be involved in the development of a variety of gastric disease.SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

    Mediat. Inflamm.

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    There is increasing evidence that proteasomes have a biological role in the extracellular alveolar space, but inflammation could change their composition. We tested whether immunoproteasome protein-containing subpopulations are present in the alveolar space of patients with lung inflammation evoking the acute respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) supernatants and cell pellet lysate from ARDS patients (n = 28) and healthy subjects (n = 10) were analyzed for the presence of immunoproteasome proteins (LMP2 and LMP7) and proteasome subtypes by western blot, chromatographic purification, and 2D-dimensional gelelectrophoresis. In all ARDS patients but not in healthy subjects LMP7 and LMP2 were observed in BAL supernatants. Proteasomes purified from pooled ARDS BAL supernatant showed an altered enzyme activity ratio. Chromatography revealed a distinct pattern with 7 proteasome subtype peaks in BAL supernatant of ARDS patients that differed from healthy subjects. Total proteasome concentration in BAL supernatant was increased in ARDS (971 ng/mL perpendicular to 1116 versus 59 perpendicular to 25; P < 0.001), and all fluorogenic substrates were hydrolyzed, albeit to a lesser extent, with inhibition by epoxomicin (P = 0.0001). Thus, we identified for the first time immunoproteasome proteins and a distinct proteasomal subtype pattern in the alveolar space of ARDS patients, presumably in response to inflammation

    Reorientation of Spin Density Waves in Cr(001) Films induced by Fe(001) Cap Layers

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    Proximity effects of 20 \AA thin Fe layers on the spin density waves (SDWs) in epitaxial Cr(001) films are revealed by neutron scattering. Unlike in bulk Cr we observe a SDW with its wave vector Q pointing along only one {100} direction which depends dramatically on the film thickness t_{Cr}. For t_{Cr} < 250 \AA the SDW propagates out-of-plane with the spins in the film plane. For t_{Cr} > 1000 \AA the SDW propagates in the film plane with the spins out-of-plane perpendicular to the in-plane Fe moments. This reorientation transition is explained by frustration effects in the antiferromagnetic interaction between Fe and Cr across the Fe/Cr interface due to steps at the interface.Comment: 4 pages (RevTeX), 3 figures (EPS

    A multimodal imaging workflow for monitoring CAR T cell therapy against solid tumor from whole-body to single-cell level

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    CAR T cell research in solid tumors often lacks spatiotemporal information and therefore, there is a need for a molecular tomography to facilitate high-throughput preclinical monitoring of CAR T cells. Furthermore, a gap exists between macro- and microlevel imaging data to better assess intratumor infiltration of therapeutic cells. We addressed this challenge by combining 3D ”Computer tomography bioluminescence tomography (”CT/BLT), light-sheet fluorescence microscopy (LSFM) and cyclic immunofluorescence (IF) staining. Methods: NSG mice with subcutaneous AsPC1 xenograft tumors were treated with EGFR CAR T cell (± IL-2) or control BDCA-2 CAR T cell (± IL-2) (n = 7 each). Therapeutic T cells were genetically modified to co-express the CAR of interest and the luciferase CBR2opt. IL-2 was administered s.c. under the xenograft tumor on days 1, 3, 5 and 7 post-therapy-initiation at a dose of 25,000 IU/mouse. CAR T cell distribution was measured in 2D BLI and 3D ”CT/BLT every 3-4 days. On day 6, 4 tumors were excised for cyclic IF where tumor sections were stained with a panel of 25 antibodies. On day 6 and 13, 8 tumors were excised from rhodamine lectin-preinjected mice, permeabilized, stained for CD3 and imaged by LSFM. Results: 3D ”CT/BLT revealed that CAR T cells pharmacokinetics is affected by antigen recognition, where CAR T cell tumor accumulation based on target-dependent infiltration was significantly increased in comparison to target-independent infiltration, and spleen accumulation was delayed. LSFM supported these findings and revealed higher T cell accumulation in target-positive groups at day 6, which also infiltrated the tumor deeper. Interestingly, LSFM showed that most CAR T cells accumulate at the tumor periphery and around vessels. Surprisingly, LSFM and cyclic IF revealed that local IL-2 application resulted in early-phase increased proliferation, but long-term overstimulation of CAR T cells, which halted the early added therapeutic effect. Conclusion: Overall, we demonstrated that 3D ”CT/BLT is a valuable non-isotope-based technology for whole-body cell therapy monitoring and investigating CAR T cell pharmacokinetics. We also presented combining LSFM and MICS for ex vivo 3D- and 2D-microscopy tissue analysis to assess intratumoral therapeutic cell distribution and status
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