Stationarity of multivariate particle systems

A particle system is a family of i.i.d. stochastic processes with values translated by Poisson points. We obtain conditions that ensure the stationarity in time of the particle system in RdRd and in some cases provide a full characterisation of the stationarity property. In particular, a full characterisation of stationary multivariate Brown–Resnick processes is given.

An optimized in vitro model of the respiratory tract wall to study particle cell interactions

As a part of the respiratory tissue barrier, lung epithelial cells play an important role against the penetration of the body by inhaled particulate foreign materials. In most cell culture models, which are designed to study particle-cell interactions, the cells are immersed in medium. This does not reflect the physiological condition of lung epithelial cells which are exposed to air, separated from it only by a very thin liquid lining layer with a surfactant film at the air-liquid interface. In this study, A549 epithelial cells were grown on microporous membranes in a two chamber system. After the formation of a confluent monolayer the cells were exposed to air. The morphology of the cells and the expression of tight junction proteins were studied with confocal laser scanning and transmission electron microscopy. Air-exposed cells maintained monolayer structure for 2 days, expressed tight junctions and developed transepithelial electrical resistance. Surfactant was produced and released at the apical side of the air-exposed epithelial cells. In order to study particle-cell interactions fluorescent 1 microm polystyrene particles were sprayed over the epithelial surface. After 4 h, 8.8% of particles were found inside the epithelium. This fraction increased to 38% after 24 h. During all observations, particles were always found in the cells but never between them. In this study, we present an in vitro model of the respiratory tract wall consisting of air-exposed lung epithelial cells covered by a liquid lining layer with a surfactant film to study particle-cell interactions.

A novel exposure system for the efficient and controlled deposition of aerosol particles onto cell cultures

Epidemiologic studies have shown correlations between morbidity and particles < or = 2.5 microm generated from pollution processes and manufactured nanoparticles. Thereby nanoparticles seem to play a specific role. The interaction of particles with the lung, the main pathway of undesired particle uptake, is poorly understood. In most studies investigating these interactions in vitro, particle deposition differs greatly from the in vivo situation, causing controversial results. We present a nanoparticle deposition chamber to expose lung cells mimicking closely the particle deposition conditions in the lung. In this new deposition chamber, particles are deposited very efficiently, reproducibly, and uniformly onto the cell culture, a key aspect if cell responses are quantified in respect to the deposited particle number. In situ analyses of the lung cells, e.g., the ciliary beat frequency, indicative of the defense capability of the cells, are complemented by off-line biochemical, physiological, and morphological cell analyses.

A dose-controlled system for air-liquid interface cell exposure and application to zinc oxide nanoparticles

BACKGROUND: Engineered nanoparticles are becoming increasingly ubiquitous and their toxicological effects on human health, as well as on the ecosystem, have become a concern. Since initial contact with nanoparticles occurs at the epithelium in the lungs (or skin, or eyes), in vitro cell studies with nanoparticles require dose-controlled systems for delivery of nanoparticles to epithelial cells cultured at the air-liquid interface. RESULTS: A novel air-liquid interface cell exposure system (ALICE) for nanoparticles in liquids is presented and validated. The ALICE generates a dense cloud of droplets with a vibrating membrane nebulizer and utilizes combined cloud settling and single particle sedimentation for fast (~10 min; entire exposure), repeatable (<12%), low-stress and efficient delivery of nanoparticles, or dissolved substances, to cells cultured at the air-liquid interface. Validation with various types of nanoparticles (Au, ZnO and carbon black nanoparticles) and solutes (such as NaCl) showed that the ALICE provided spatially uniform deposition (<1.6% variability) and had no adverse effect on the viability of a widely used alveolar human epithelial-like cell line (A549). The cell deposited dose can be controlled with a quartz crystal microbalance (QCM) over a dynamic range of at least 0.02-200 mug/cm(2). The cell-specific deposition efficiency is currently limited to 0.072 (7.2% for two commercially available 6-er transwell plates), but a deposition efficiency of up to 0.57 (57%) is possible for better cell coverage of the exposure chamber. Dose-response measurements with ZnO nanoparticles (0.3-8.5 mug/cm(2)) showed significant differences in mRNA expression of pro-inflammatory (IL-8) and oxidative stress (HO-1) markers when comparing submerged and air-liquid interface exposures. Both exposure methods showed no cellular response below 1 mug/cm(2 )ZnO, which indicates that ZnO nanoparticles are not toxic at occupationally allowed exposure levels. CONCLUSION: The ALICE is a useful tool for dose-controlled nanoparticle (or solute) exposure of cells at the air-liquid interface. Significant differences between cellular response after ZnO nanoparticle exposure under submerged and air-liquid interface conditions suggest that pharmaceutical and toxicological studies with inhaled (nano-)particles should be performed under the more realistic air-liquid interface, rather than submerged cell conditions.

Expression, purification, and projection structure by single particle electron microscopy of functional human TRPM4 heterologously expressed in Xenopus laevis oocytes

Despite efforts implicating the cationic channel transient receptor potential melastatin member 4 (TRPM4) to cardiac, nervous, and immunological pathologies, little is known about its structure and function. In this study, we optimized the requirements for purification and extraction of functional human TRPM4 protein and investigated its supra-molecular assembly. We selected the Xenopus laevis oocyte expression system because it lacks endogenous TRPM4 expression, it is known to overexpress functional human membrane channels, can be used for structure-function analysis within the same system, and is easily scaled to improve yield and develop moderate throughput capabilities through the use of robotics. Negative-stain electron microscopy (EM) revealed various sized low-resolution particles. Single particle analysis identified the majority of the projections represented the monomeric form with additional oligomeric structures potentially characterized as tetramers. Two-electrode voltage clamp electrophysiology demonstrated that human TRPM4 is functionally expressed at the oocyte plasma membrane. This study opens the door for medium-throughput screening and structure-function determination of this important therapeutically relevant target.

An adjustable focusing system for a 2 MeV H- ion beam line based on permanent magnet quadrupoles

A compact adjustable focusing system for a 2 MeV H- RFQ Linac is designed, constructed and tested based on four permanent magnet quadrupoles (PMQ). A PMQ model is realised using finite element simulations, providing an integrated field gradient of 2.35 T with a maximal field gradient of 57 T/m. A prototype is constructed and the magnetic field is measured, demonstrating good agreement with the simulation. Particle track simulations provide initial values for the quadrupole positions. Accordingly, four PMQs are constructed and assembled on the beam line, their positions are then tuned to obtain a minimal beam spot size of (1.2 x 2.2) mm^2 on target. This paper describes an adjustable PMQ beam line for an external ion beam. The novel compact design based on commercially available NdFeB magnets allows high flexibility for ion beam applications.

Measurement with the ATLAS detector of multi-particle azimuthal correlations in p+Pb collisions at sqrtsNN=5.02 TeV

In order to study further the long-range correlations ("ridge") observed recently in p+Pb collisions at sqrt(s_NN) =5.02 TeV, the second-order azimuthal anisotropy parameter of charged particles, v_2, has been measured with the cumulant method using the ATLAS detector at the LHC. In a data sample corresponding to an integrated luminosity of approximately 1 microb^(-1), the parameter v_2 has been obtained using two- and four-particle cumulants over the pseudorapidity range |eta|<2.5. The results are presented as a function of transverse momentum and the event activity, defined in terms of the transverse energy summed over 3.1particle correlation methods, and to predictions from hydrodynamic models of p+Pb collisions. Despite the small transverse spatial extent of the p+Pb collision system, the large magnitude of v_2 and its similarity to hydrodynamic predictions provide additional evidence for the importance of final-state effects in p+Pb reactions.

Expression, purification, and structural insights for the human uric acid transporter, GLUT9, using the Xenopus laevis oocytes system.

The urate transporter, GLUT9, is responsible for the basolateral transport of urate in the proximal tubule of human kidneys and in the placenta, playing a central role in uric acid homeostasis. GLUT9 shares the least homology with other members of the glucose transporter family, especially with the glucose transporting members GLUT1-4 and is the only member of the GLUT family to transport urate. The recently published high-resolution structure of XylE, a bacterial D-xylose transporting homologue, yields new insights into the structural foundation of this GLUT family of proteins. While this represents a huge milestone, it is unclear if human GLUT9 can benefit from this advancement through subsequent structural based targeting and mutagenesis. Little progress has been made toward understanding the mechanism of GLUT9 since its discovery in 2000. Before work can begin on resolving the mechanisms of urate transport we must determine methods to express, purify and analyze hGLUT9 using a model system adept in expressing human membrane proteins. Here, we describe the surface expression, purification and isolation of monomeric protein, and functional analysis of recombinant hGLUT9 using the Xenopus laevis oocyte system. In addition, we generated a new homology-based high-resolution model of hGLUT9 from the XylE crystal structure and utilized our purified protein to generate a low-resolution single particle reconstruction. Interestingly, we demonstrate that the functional protein extracted from the Xenopus system fits well with the homology-based model allowing us to generate the predicted urate-binding pocket and pave a path for subsequent mutagenesis and structure-function studies.

Range-based Weighted-likelihood Particle Filter for RSS-based Indoor Tracking

Attractive business cases in various application fields contribute to the sustained long-term interest in indoor localization and tracking by the research community. Location tracking is generally treated as a dynamic state estimation problem, consisting of two steps: (i) location estimation through measurement, and (ii) location prediction. For the estimation step, one of the most efficient and low-cost solutions is Received Signal Strength (RSS)-based ranging. However, various challenges - unrealistic propagation model, non-line of sight (NLOS), and multipath propagation - are yet to be addressed. Particle filters are a popular choice for dealing with the inherent non-linearities in both location measurements and motion dynamics. While such filters have been successfully applied to accurate, time-based ranging measurements, dealing with the more error-prone RSS based ranging is still challenging. In this work, we address the above issues with a novel, weighted likelihood, bootstrap particle filter for tracking via RSS-based ranging. Our filter weights the individual likelihoods from different anchor nodes exponentially, according to the ranging estimation. We also employ an improved propagation model for more accurate RSS-based ranging, which we suggested in recent work. We implemented and tested our algorithm in a passive localization system with IEEE 802.15.4 signals, showing that our proposed solution largely outperforms a traditional bootstrap particle filter.

Passively Track WiFi Users with an Enhanced Particle Filter using Power-based Ranging

Passive positioning systems produce user location information for third-party providers of positioning services. Since the tracked wireless devices do not participate in the positioning process, passive positioning can only rely on simple, measurable radio signal parameters, such as timing or power information. In this work, we provide a passive tracking system for WiFi signals with an enhanced particle filter using fine-grained power-based ranging. Our proposed particle filter provides an improved likelihood function on observation parameters and is equipped with a modified coordinated turn model to address the challenges in a passive positioning system. The anchor nodes for WiFi signal sniffing and target positioning use software defined radio techniques to extract channel state information to mitigate multipath effects. By combining the enhanced particle filter and a set of enhanced ranging methods, our system can track mobile targets with an accuracy of 1.5m for 50% and 2.3m for 90% in a complex indoor environment. Our proposed particle filter significantly outperforms the typical bootstrap particle filter, extended Kalman filter and trilateration algorithms.

Transmission of Mycobacterium chimaera from Heater-Cooler Units during Cardiac Surgery despite an Ultraclean Air Ventilation System.

Heater-cooler units (HCUs) were recently identified as a source of Mycobacterium chimaera causing surgical site infections. We investigated transmission of this bacterium from HCUs to the surgical field by using a thermic anemometer and particle counter, videotape of an operating room equipped with an ultraclean laminar airflow ventilation system, and bacterial culture sedimentation plates in a nonventilated room. Smoke from the HCU reached the surgical field in 23 s by merging with ultraclean air. The HCU produced on average 5.2, 139, and 14.8 particles/min in the surgical field at positions Off, On/oriented toward, and On/oriented away, respectively. Culture plates were positive for M. chimaera <5 m from the HCU in the test room. These experiments confirm airborne transmission of M. chimaera aerosols from a contaminated HCU to an open surgical field despite ultraclean air ventilation. Efforts to mitigate infectious risks during surgery should consider contamination from water sources and airflow-generating devices.

Particle tracking at cryogenic temperatures: the Fast Annihilation Cryogenic Tracking (FACT) detector for the AEgIS antimatter gravity experiment

The AEgIS experiment is an interdisciplinary collaboration between atomic, plasma and particle physicists, with the scientific goal of performing the first precision measurement of the Earth's gravitational acceleration on antimatter. The principle of the experiment is as follows: cold antihydrogen atoms are synthesized in a Penning-Malmberg trap and are Stark accelerated towards a moiré deflectometer, the classical counterpart of an atom interferometer, and annihilate on a position sensitive detector. Crucial to the success of the experiment is an antihydrogen detector that will be used to demonstrate the production of antihydrogen and also to measure the temperature of the anti-atoms and the creation of a beam. The operating requirements for the detector are very challenging: it must operate at close to 4 K inside a 1 T solenoid magnetic field and identify the annihilation of the antihydrogen atoms that are produced during the 1 μs period of antihydrogen production. Our solution—called the FACT detector—is based on a novel multi-layer scintillating fiber tracker with SiPM readout and off the shelf FPGA based readout system. This talk will present the design of the FACT detector and detail the operation of the detector in the context of the AEgIS experiment.