Cerebral Biomarkers and Blood-Brain Barrier Integrity in Preeclampsia

Cerebral complications in preeclampsia contribute substantially to maternal mortality and morbidity. There is a lack of reliable and accessible predictors for preeclampsia-related cerebral complications. In this study, plasma from women with preeclampsia (n = 28), women with normal pregnancies (n = 28) and non-pregnant women (n = 16) was analyzed for concentrations of the cerebral biomarkers neurofilament light (NfL), tau, neuron-specific enolase (NSE) and S100B. Then, an in vitro blood–brain barrier (BBB) model, based on the human cerebral microvascular endothelial cell line (hCMEC/D3), was employed to assess the effect of plasma from the three study groups. Transendothelial electrical resistance (TEER) was used as an estimation of BBB integrity. NfL and tau are proteins expressed in axons, NSE in neurons and S100B in glial cells and are used as biomarkers for neurological injury in other diseases such as dementia, traumatic brain injury and hypoxic brain injury. Plasma concentrations of NfL, tau, NSE and S100B were all higher in women with preeclampsia compared with women with normal pregnancies (8.85 vs. 5.25 ng/L, p < 0.001; 2.90 vs. 2.40 ng/L, p < 0.05; 3.50 vs. 2.37 µg/L, p < 0.001 and 0.08 vs. 0.05 µg/L, p < 0.01, respectively). Plasma concentrations of NfL were also higher in women with preeclampsia compared with non-pregnant women (p < 0.001). Higher plasma concentrations of the cerebral biomarker NfL were associated with decreased TEER (p = 0.002) in an in vitro model of the BBB, a finding which indicates that NfL could be a promising biomarker for BBB alterations in preeclampsia

Calibration and Characterization of the IceCube Photomultiplier Tube

Over 5,000 PMTs are being deployed at the South Pole to compose the IceCube neutrino observatory. Many are placed deep in the ice to detect Cherenkov light emitted by the products of high-energy neutrino interactions, and others are frozen into tanks on the surface to detect particles from atmospheric cosmic ray showers. IceCube is using the 10-inch diameter R7081-02 made by Hamamatsu Photonics. This paper describes the laboratory characterization and calibration of these PMTs before deployment. PMTs were illuminated with pulses ranging from single photons to saturation level. Parameterizations are given for the single photoelectron charge spectrum and the saturation behavior. Time resolution, late pulses and afterpulses are characterized. Because the PMTs are relatively large, the cathode sensitivity uniformity was measured. The absolute photon detection efficiency was calibrated using Rayleigh-scattered photons from a nitrogen laser. Measured characteristics are discussed in the context of their relevance to IceCube event reconstruction and simulation efforts.Comment: 40 pages, 12 figure

Repetitive use of levosimendan for treatment of chronic advanced heart failure: Clinical evidence, practical considerations, and perspectives: An expert panel consensus

Background The intravenous inodilator levosimendan was developed for the treatment of patients with acutely decompensated heart failure. In the last decade scientific and clinical interest has arisen for its repetitive or intermittent use in patients with advanced chronic, but not necessarily acutely decompensated, heart failure. Recent studies have suggested long-lasting favourable effects of levosimendan when administered repetitively, in terms of haemodynamic parameters, neurohormonal and inflammatory markers, and clinical outcomes. The existing data, however, requires further exploration to allow for definitive conclusions on the safety and clinical efficacy of repetitive use of levosimendan. Methods and results A panel of 30 experts from 15 countries convened to review and discuss the existing data, and agreed on the patient groups that can be considered to potentially benefit from intermittent treatment with levosimendan. The panel gave recommendations regarding patient dosing and monitoring, derived from the available evidence and from clinical experience. Conclusions The current data suggest that in selected patients and support out-of-hospital care, intermittent/repetitive levosimendan can be used in advanced heart failure to maintain patient stability. Further studies are needed to focus on morbidity and mortality outcomes, dosing intervals, and patient monitoring. Recommendations for the design of further clinical studies are made

Detection of Atmospheric Muon Neutrinos with the IceCube 9-String Detector

The IceCube neutrino detector is a cubic kilometer TeV to PeV neutrino detector under construction at the geographic South Pole. The dominant population of neutrinos detected in IceCube is due to meson decay in cosmic-ray air showers. These atmospheric neutrinos are relatively well-understood and serve as a calibration and verification tool for the new detector. In 2006, the detector was approximately 10% completed, and we report on data acquired from the detector in this configuration. We observe an atmospheric neutrino signal consistent with expectations, demonstrating that the IceCube detector is capable of identifying neutrino events. In the first 137.4 days of livetime, 234 neutrino candidates were selected with an expectation of 211 +/- 76.1(syst.) +/- 14.5(stat.) events from atmospheric neutrinos

Lattice-based proof of a shuffle

In this paper we present the first fully post-quantum proof of a shuffle for RLWE encryption schemes. Shuffles are commonly used to construct mixing networks (mix-nets), a key element to ensure anonymity in many applications such as electronic voting systems. They should preserve anonymity even against an attack using quantum computers in order to guarantee long-term privacy. The proof presented in this paper is built over RLWE commitments which are perfectly binding and computationally hiding under the RLWE assumption, thus achieving security in a post-quantum scenario. Furthermore we provide a new definition for a secure mixing node (mix-node) and prove that our construction satisfies this definition

Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla

<p>Abstract</p> <p>Background</p> <p>Omptins are a family of outer membrane proteases that have spread by horizontal gene transfer in Gram-negative bacteria that infect vertebrates or plants. Despite structural similarity, the molecular functions of omptins differ in a manner that reflects the life style of their host bacteria. To simulate the molecular adaptation of omptins, we applied site-specific mutagenesis to make Epo of the plant pathogenic <it>Erwinia pyrifoliae </it>exhibit virulence-associated functions of its close homolog, the plasminogen activator Pla of <it>Yersinia pestis</it>. We addressed three virulence-associated functions exhibited by Pla, i.e., proteolytic activation of plasminogen, proteolytic degradation of serine protease inhibitors, and invasion into human cells.</p> <p>Results</p> <p>Pla and Epo expressed in <it>Escherichia coli </it>are both functional endopeptidases and cleave human serine protease inhibitors, but Epo failed to activate plasminogen and to mediate invasion into a human endothelial-like cell line. Swapping of ten amino acid residues at two surface loops of Pla and Epo introduced plasminogen activation capacity in Epo and inactivated the function in Pla. We also compared the structure of Pla and the modeled structure of Epo to analyze the structural variations that could rationalize the different proteolytic activities. Epo-expressing bacteria managed to invade human cells only after all extramembranous residues that differ between Pla and Epo and the first transmembrane β-strand had been changed.</p> <p>Conclusions</p> <p>We describe molecular adaptation of a protease from an environmental setting towards a virulence factor detrimental for humans. Our results stress the evolvability of bacterial β-barrel surface structures and the environment as a source of progenitor virulence molecules of human pathogens.</p

On the selection of AGN neutrino source candidates for a source stacking analysis with neutrino telescopes

The sensitivity of a search for sources of TeV neutrinos can be improved by grouping potential sources together into generic classes in a procedure that is known as source stacking. In this paper, we define catalogs of Active Galactic Nuclei (AGN) and use them to perform a source stacking analysis. The grouping of AGN into classes is done in two steps: first, AGN classes are defined, then, sources to be stacked are selected assuming that a potential neutrino flux is linearly correlated with the photon luminosity in a certain energy band (radio, IR, optical, keV, GeV, TeV). Lacking any secure detailed knowledge on neutrino production in AGN, this correlation is motivated by hadronic AGN models, as briefly reviewed in this paper. The source stacking search for neutrinos from generic AGN classes is illustrated using the data collected by the AMANDA-II high energy neutrino detector during the year 2000. No significant excess for any of the suggested groups was found.Comment: 43 pages, 12 figures, accepted by Astroparticle Physic

An Evaluation Model For Web-based 3D Mass Customization Toolkit Design

The development of geometric modelling technologies and web technologies provides the ability to present a virtual 3D product in a mass customization (MC) toolkit. Compared with 2D graphic toolkits, 3D toolkit design requires better consideration of individual customer needs, consumer and toolkit interaction, and also a means of integrating with the underlying technical infrastructure. However, there is currently no widely accepted model or criteria to regulate and evaluate 3D MC toolkit design. Given these considerations, in this paper we provide an evaluation model for web-based 3D toolkits and a heuristic evaluation of two representative commercial web-based 3D toolkits. The evaluation results indicate the usefulness and effectiveness of the model as a scale for evaluating 3D toolkits. It also reveals that despite a fair amount of effort that has been devoted to theoretical research, current 3D toolkits are still at an early development stage. We therefore conclude this paper by identifying and encouraging further topics and questions as directions for future research

Seniors' experiences of living in special housing accommodation

This article presents a hermeneutic phenomenological analysis of interview material in which 12 seniors living in Special Housing Accommodation (SHA) facilities reflect on the experience of living in such facilities. Of particular interest in the analysis is living in a SHA as a phenomenon. The finding shows that the phenomenon of lived experience in a SHA seems to be a state of ambiguity regarding one's existence, which is made up of several constituents (elements of meaning). The analysis contributes to the understanding of how the phenomenon of SHA living is coming into existence as a need, due to an individual's failing health; however, the SHA is not considered to be a true home. Accordingly, this has consequences to the subject position for the seniors in that they have to navigate between existing and not existing. The seniors learn to cope with living in the SHA by lowering their expectations of life and existence while the SHA provides the prerequisites for their existence. An implication for promoting care is to support the seniors to enable a full existence of life within SHA living

Time projection chambers for the T2K near detectors

The T2K experiment is designed to study neutrino oscillation properties by directing a high intensity neutrino beam produced at J-PARC in Tokai, Japan, towards the large Super-Kamiokande detector located 295 km away, in Kamioka, Japan. The experiment includes a sophisticated near detector complex, 280 m downstream of the neutrino production target in order to measure the properties of the neutrino beam and to better understand neutrino interactions at the energy scale below a few GeV. A key element of the near detectors is the ND280 tracker, consisting of two active scintillator-bar target systems surrounded by three large time projection chambers (TPCs) for charged particle tracking. The data collected with the tracker is used to study charged current neutrino interaction rates and kinematics prior to oscillation, in order to reduce uncertainties in the oscillation measurements by the far detector. The tracker is surrounded by the former UA1/Nomad dipole magnet and the TPCs measure the charges, momenta, and particle types of charged particles passing through them. Novel features of the TPC design include its rectangular box layout constructed from composite panels, the use of bulk micromegas detectors for gas amplification, electronics readout based on a new ASIC, and a photoelectron calibration system. This paper describes the design and construction of the TPCs, the micromegas modules, the readout electronics, the gas handling system, and shows the performance of the TPCs as deduced from measurements with particle beams, cosmic rays, and the calibration system