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Sample records for localized bbb opening

  1. Neuronavigation-guided focused ultrasound-induced blood-brain barrier opening: A preliminary study in swine

    Science.gov (United States)

    Liu, Hao-Li; Tsai, Hong-Chieh; Lu, Yu-Jen; Wei, Kuo-Chen

    2012-11-01

    FUS-induced BBB opening is a promising technique for noninvasive and local delivery of drugs into the brain. Here we propose the novel use of a neuronavigation system to guide the FUS-induced BBB opening procedure, and investigate its feasibility in vivo in large animals. We developed an interface between the neuronavigator and FUS to allow guidance of the focal energy produced by the FUS transducer. The system was tested in 29 pigs by more than 40 sonication procedures and evaluated by MRI. Gd-DTPA concentration was quantitated in vivo by MRI R1 relaxometry and compared by ICP-OES assay. Brain histology after FUS exposure was investigated by HE and TUNEL staining. Neuronavigation could successfully guide the focal beam with comparable precision to neurosurgical stereotactic procedures (2.3 ± 0.9 mm). FUS pressure of 0.43 MPa resulted in consistent BBB-opening. Neuronavigation-guided BBB-opening increased Gd-DTPA deposition by up to 1.83 mM (140% increase). MR relaxometry demonstrated high correlation to ICP-OES measurements (r2 = 0.822), suggesting that Gd-DTPA deposition can be directly measured by imaging. Neuronavigation could provide sufficient precision for guiding FUS to temporally and locally open the BBB. Gd-DTPA deposition in the brain could be quantified by MR relaxometry, providing a potential tool for the in vivo quantification of therapeutic agents in CNS disease treatment.

  2. Focused ultrasound-induced blood-brain barrier opening to enhance temozolomide delivery for glioblastoma treatment: a preclinical study.

    Directory of Open Access Journals (Sweden)

    Kuo-Chen Wei

    Full Text Available The purpose of this study is to assess the preclinical therapeutic efficacy of magnetic resonance imaging (MRI-monitored focused ultrasound (FUS-induced blood-brain barrier (BBB disruption to enhance Temozolomide (TMZ delivery for improving Glioblastoma Multiforme (GBM treatment. MRI-monitored FUS with microbubbles was used to transcranially disrupt the BBB in brains of Fisher rats implanted with 9L glioma cells. FUS-BBB opening was spectrophotometrically determined by leakage of dyes into the brain, and TMZ was quantitated in cerebrospinal fluid (CSF and plasma by LC-MS\\MS. The effects of treatment on tumor progression (by MRI, animal survival and brain tissue histology were investigated. Results demonstrated that FUS-BBB opening increased the local accumulation of dyes in brain parenchyma by 3.8-/2.1-fold in normal/tumor tissues. Compared to TMZ alone, combined FUS treatment increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced the 7-day tumor progression ratio from 24.03 to 5.06, and extended the median survival from 20 to 23 days. In conclusion, this study provided preclinical evidence that FUS BBB-opening increased the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting its clinical potential for improving current brain tumor treatment.

  3. Molecules of various pharmacologically-relevant sizes can cross the ultrasound-induced blood-brain barrier opening in vivo.

    Science.gov (United States)

    Choi, James J; Wang, Shougang; Tung, Yao-Sheng; Morrison, Barclay; Konofagou, Elisa E

    2010-01-01

    Focused ultrasound (FUS) is hereby shown to noninvasively and selectively deliver compounds at pharmacologically relevant molecular weights through the opened blood-brain barrier (BBB). A complete examination on the size of the FUS-induced BBB opening, the spatial distribution of the delivered agents and its dependence on the agent's molecular weight were imaged and quantified using fluorescence microscopy. BBB opening in mice (n=13) was achieved in vivo after systemic administration of microbubbles and subsequent application of pulsed FUS (frequency: 1.525MHz, peak-rarefactional pressure in situ: 570 kPa) to the left murine hippocampus through the intact skin and skull. BBB-impermeant, fluorescent-tagged dextrans at three distinct molecular weights spanning over several orders of magnitude were systemically administered and acted as model therapeutic compounds. First, dextrans of 3 and 70 kDa were delivered trans-BBB while 2000 kDa dextran was not. Second, compared with 70 kDa dextran, a higher concentration of 3 kDa dextran was delivered through the opened BBB. Third, the 3 and 70 kDa dextrans were both diffusely distributed throughout the targeted brain region. However, high concentrations of 70 kDa dextran appeared more punctated throughout the targeted region. In conclusion, FUS combined with microbubbles opened the BBB sufficiently to allow passage of compounds of at least 70 kDa, but not greater than 2000 kDa into the brain parenchyma. This noninvasive and localized BBB opening technique could, thus, provide a unique means for the delivery of compounds of several magnitudes of kDa that include agents with shown therapeutic promise in vitro but whose in vivo translation has been hampered by their associated BBB impermeability. (E-mail: ek2191@columbia.edu).

  4. Noninvasive Blood-Brain Barrier Opening in Live Mice

    Science.gov (United States)

    Choi, James J.; Pernot, Mathieu; Small, Scott; Konofagou, Elisa E.

    2006-05-01

    Most therapeutic agents cannot be delivered to the brain because of brain's natural defense: the Blood-Brain Barrier (BBB). It has recently been shown that Focused Ultrasound (FUS) can produce reversible and localized BBB opening in the brain when applied in the presence of ultrasound contrast agents post-craniotomy in rabbits [1]. However, a major limitation of ultrasound in the brain is the strong phase aberration and attenuation of the skull bone, and, as a result, no study of trans-cranial ultrasound-targeted drug treatment in the brain in vivo has been reported as of yet. In this study, the feasibility of BBB opening in the hippocampus of wildtype mice using FUS through the intact skull and skin was investigated. In order to investigate the effect of the skull, simulations of ultrasound wave propagation (1.5 MHz) through the skull using μCT data, and needle hydrophone measurements through an ex-vivo skull were made. The pressure field showed minimal attenuation (18% of the pressure amplitude) and a well-focused pattern through the left and right halves of the parietal bone. In experiments in vivo, the brains of four mice were sonicated through intact skull and skin. Ultrasound sonications (burst length: 20 ms; duty cycle: 20%; acoustic pressure range: 2.0 to 2.7 MPa) was applied 5 times for 30 s per shot with a 30 s delay between shots. Prior to sonication, ultrasound contrast agents (Optison; 10 μL) were injected intravenously. Contrast material enhanced high resolution MR Imaging (9.4 Tesla) was able to distinguish opening of large vessels in the region of the hippocampus. These results demonstrate the feasibility of locally opening the BBB in the mouse hippocampus using focused ultrasound through intact skull and skin. Future investigations will deal with optimization and reproducibility of the technique as well as application on Alzheimer's-model mice.

  5. Real-time monitoring of focused ultrasound blood-brain barrier opening via subharmonic acoustic emission detection: implementation of confocal dual-frequency piezoelectric transducers

    Science.gov (United States)

    Tsai, Chih-Hung; Zhang, Jia-Wei; Liao, Yi-Yi; Liu, Hao-Li

    2016-04-01

    Burst-tone focused ultrasound exposure in the presence of microbubbles has been demonstrated to be effective at inducing temporal and local opening of the blood-brain barrier (BBB), which promises significant clinical potential to deliver therapeutic molecules into the central nervous system (CNS). Traditional contrast-enhanced imaging confirmation after focused ultrasound (FUS) exposure serves as a post-operative indicator of the effectiveness of FUS-BBB opening, however, an indicator that can concurrently report the BBB status and BBB-opening effectiveness is required to provide effective feedback to implement this treatment clinically. In this study, we demonstrate the use of subharmonic acoustic emission detection with implementation on a confocal dual-frequency piezoelectric ceramic structure to perform real-time monitoring of FUS-BBB opening. A confocal dual-frequency (0.55 MHz/1.1 MHz) focused ultrasound transducer was designed. The 1.1 MHz spherically-curved ceramic was employed to deliver FUS exposure to induce BBB-opening, whereas the outer-ring 0.55 MHz ceramic was employed to detect the subharmonic acoustic emissions originating from the target position. In stage-1 experiments, we employed spectral analysis and performed an energy spectrum density (ESD) calculation. An optimized 0.55 MHz ESD level change was shown to effectively discriminate the occurrence of BBB-opening. Wideband acoustic emissions received from 0.55 MHz ceramics were also analyzed to evaluate its correlations with erythrocyte extravasations. In stage-2 real-time monitoring experiments, we applied the predetermined ESD change as a detection threshold in PC-controlled algorithm to predict the FUS exposure intra-operatively. In stage-1 experiment, we showed that subharmonic ESD presents distinguishable dynamics between intact BBB and opened BBB, and therefore a threshold ESD change level (5.5 dB) can be identified for BBB-opening prediction. Using this ESD change threshold detection as a

  6. Real-time monitoring of focused ultrasound blood-brain barrier opening via subharmonic acoustic emission detection: implementation of confocal dual-frequency piezoelectric transducers

    International Nuclear Information System (INIS)

    Tsai, Chih-Hung; Zhang, Jia-Wei; Liao, Yi-Yi; Liu, Hao-Li

    2016-01-01

    Burst-tone focused ultrasound exposure in the presence of microbubbles has been demonstrated to be effective at inducing temporal and local opening of the blood-brain barrier (BBB), which promises significant clinical potential to deliver therapeutic molecules into the central nervous system (CNS). Traditional contrast-enhanced imaging confirmation after focused ultrasound (FUS) exposure serves as a post-operative indicator of the effectiveness of FUS-BBB opening, however, an indicator that can concurrently report the BBB status and BBB-opening effectiveness is required to provide effective feedback to implement this treatment clinically. In this study, we demonstrate the use of subharmonic acoustic emission detection with implementation on a confocal dual-frequency piezoelectric ceramic structure to perform real-time monitoring of FUS-BBB opening. A confocal dual-frequency (0.55 MHz/1.1 MHz) focused ultrasound transducer was designed. The 1.1 MHz spherically-curved ceramic was employed to deliver FUS exposure to induce BBB-opening, whereas the outer-ring 0.55 MHz ceramic was employed to detect the subharmonic acoustic emissions originating from the target position. In stage-1 experiments, we employed spectral analysis and performed an energy spectrum density (ESD) calculation. An optimized 0.55 MHz ESD level change was shown to effectively discriminate the occurrence of BBB-opening. Wideband acoustic emissions received from 0.55 MHz ceramics were also analyzed to evaluate its correlations with erythrocyte extravasations. In stage-2 real-time monitoring experiments, we applied the predetermined ESD change as a detection threshold in PC-controlled algorithm to predict the FUS exposure intra-operatively. In stage-1 experiment, we showed that subharmonic ESD presents distinguishable dynamics between intact BBB and opened BBB, and therefore a threshold ESD change level (5.5 dB) can be identified for BBB-opening prediction. Using this ESD change threshold detection as a

  7. Computing the blood brain barrier (BBB) diffusion coefficient: A molecular dynamics approach

    Energy Technology Data Exchange (ETDEWEB)

    Shamloo, Amir, E-mail: shamloo@sharif.edu; Pedram, Maysam Z.; Heidari, Hossein; Alasty, Aria, E-mail: aalasti@sharif.edu

    2016-07-15

    Various physical and biological aspects of the Blood Brain Barrier (BBB) structure still remain unfolded. Therefore, among the several mechanisms of drug delivery, only a few have succeeded in breaching this barrier, one of which is the use of Magnetic Nanoparticles (MNPs). However, a quantitative characterization of the BBB permeability is desirable to find an optimal magnetic force-field. In the present study, a molecular model of the BBB is introduced that precisely represents the interactions between MNPs and the membranes of Endothelial Cells (ECs) that form the BBB. Steered Molecular Dynamics (SMD) simulations of the BBB crossing phenomenon have been carried out. Mathematical modeling of the BBB as an input-output system has been considered from a system dynamics modeling viewpoint, enabling us to analyze the BBB behavior based on a robust model. From this model, the force profile required to overcome the barrier has been extracted for a single NP from the SMD simulations at a range of velocities. Using this data a transfer function model has been obtained and the diffusion coefficient is evaluated. This study is a novel approach to bridge the gap between nanoscale models and microscale models of the BBB. The characteristic diffusion coefficient has the nano-scale molecular effects inherent, furthermore reducing the computational costs of a nano-scale simulation model and enabling much more complex studies to be conducted. - Highlights: • Molecular dynamics simulation of crossing nano-particles through the BBB membrane at different velocities. • Recording the position of nano-particle and the membrane-NP interaction force profile. • Identification of a frequency domain model for the membrane. • Calculating the diffusion coefficient based on MD simulation and identified model. • Obtaining a relation between continuum medium and discrete medium.

  8. Application of in vitro BBB model to measure permeability of nanoparticles

    International Nuclear Information System (INIS)

    Hanada, S; Kanaya, F; Yamamoto, K; Fujoka, K; Manome, Y; Inoue, Y

    2013-01-01

    In both pharmaceutical and toxicological fields, one of major issues has been the possibility of nanoparticle uptake to central nerve system. For the safe use of nanoparticles, it is integral to evaluate the permeability of nanoparticles through BBB. In our collaborative research group reported that a few nanoparticles accumulated in brain in animal experiment, as an in vitro model, we applied commercially available cell-based BBB model for establishing evaluation method, which is quick, quantitative and equivalent to in vivo assay. We assayed 30–1500 nm silica and surface charge dependent Qdots. Our results showed the size-dependency and the surface modification dependency. We compared our assay to several animal experiments. There are both equivalence and discrepancy with animal experiments. Our BBB model can be useful tools for evaluating size-dependent permeability, but not for surface modification-dependent permeability. Our BBB assay is non-serum assay and we have not adequately reflected the serum-related interaction between nanoparticles and cell surfaces. To clear up the discrepancy of our BBB model, serum-based assay and low-concentration detection will be needed.

  9. Análise produtiva da utilização de touros BBB e Charoleses em vacadas comerciais Charolais and BBB bulls at suckling cow herds

    Directory of Open Access Journals (Sweden)

    A. Perdigão

    2007-01-01

    Full Text Available O Branco Azul Belga (BBB é uma raça bovina para cruzamentos terminais que, através de exposição em feiras, tem vindo a tentar convencer os criadores nacionais do seu interesse. Estamos como é lógico perante um efeito de marketing! Este trabalho pretende demonstrar, como contributo, o que realmente acontece quando utilizamos os touros BBB (via inseminação artificial, comparativamente com os touros de raça Charolesa, em termos de resposta reprodutiva e produtiva. Foi interessante o incremento de peso desmamado (+15%, assim como a quase inexistência de distócias (vacas todas multíparas. No entanto, a nível da inseminação artificial como instrumento zootécnico, temos de focar o incremento das dificuldades de maneio, que podem desencorajar os criadores, para a respectiva utilização.The Belgian Blue White (BBB, is a beef cattle breed for terminal crossings that have come, through exposition in fairs, trying to convince the national cattleman about its interest. We are as it is logical before a marketing effect! This work intends to demonstrate, as contribution, what really happens when we use BBB bulls (by artificial insemination, still compared with the bulls of Charolesa breed, in terms of reproductive and productive reply. The increment of weaned weight through BBB was interesting (+15%, as well as almost the inexistence of distocia (all mature cows. However, about the artificial insemination, as a livestock instrument, we have to point out the increment of the difficulties of management that can discourage the producers, for the use of the BBB breed.

  10. Acoustic cavitation-based monitoring of the reversibility and permeability of ultrasound-induced blood-brain barrier opening.

    Science.gov (United States)

    Sun, Tao; Samiotaki, Gesthimani; Wang, Shutao; Acosta, Camilo; Chen, Cherry C; Konofagou, Elisa E

    2015-12-07

    Cavitation events seeded by microbubbles have been previously reported to be associated with MR- or fluorescent-contrast enhancement after focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening. However, it is still unknown whether bubble activity can be correlated with the reversibility (the duration of opening and the likelihood of safe reinstatement) and the permeability of opened BBB, which is critical for the clinical translation of using passive cavitation detection to monitor, predict and control the opening. In this study, the dependence of acoustic cavitation on the BBB opening duration, permeability coefficient and histological damage occurrence were thus investigated. Transcranial pulsed FUS at 1.5 MHz in the presence of systemically circulating microbubbles was applied in the mouse hippocampi (n  =  60). The stable and inertial cavitation activities were monitored during sonication. Contrast-enhanced MRI was performed immediately after sonication and every 24 h up to 6 d thereafter, to assess BBB opening, brain tissue permeability and potential edema. Histological evaluations were used to assess the occurrence of neurovascular damages. It was found that stable cavitation was well correlated with: (1) the duration of the BBB opening (r(2)  =  0.77); (2) the permeability of the opened BBB (r(2)  =  0.82); (3) the likelihood of safe opening (P  cavitation dose was correlated with the resulting BBB permeability (r(2)  =  0.72). Stable cavitation was found to be more reliable than inertial cavitation at assessing the BBB opening within the pressure range used in this study. This study demonstrates that the stable cavitation response during BBB opening holds promise for predicting and controlling the restoration and pharmacokinetics of FUS-opened BBB. The stable cavitation response therefore showed great promise in predicting the BBB opening duration, enabling thus control of opening according to the drug

  11. aaBBB: The Strophic Form of Fernan Rodriguez de Calheiros 7

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    Rip Cohen

    2016-12-01

    Full Text Available The refrain of a cantiga d’amigo by Fernan Rodriguez Calheiros (B 632/V 233, heretofore misunderstood as consisting of five verses, should be taken as a 3-verse refrain with two internal rhymes in the middle verse, conforming to the strophic form aaBBB. This analysis is confirmed by two virtuoso features: the middle verse of the BBB refrain scans longer than the outer ones but corresponds to the verses of the distich; and the text constitutes an example of a BBB refrain where the third verse repeats the first.

  12. Acoustic cavitation-based monitoring of the reversibility and permeability of ultrasound-induced blood-brain barrier opening

    International Nuclear Information System (INIS)

    Sun, Tao; Samiotaki, Gesthimani; Wang, Shutao; Acosta, Camilo; Chen, Cherry C; Konofagou, Elisa E

    2015-01-01

    Cavitation events seeded by microbubbles have been previously reported to be associated with MR- or fluorescent-contrast enhancement after focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening. However, it is still unknown whether bubble activity can be correlated with the reversibility (the duration of opening and the likelihood of safe reinstatement) and the permeability of opened BBB, which is critical for the clinical translation of using passive cavitation detection to monitor, predict and control the opening. In this study, the dependence of acoustic cavitation on the BBB opening duration, permeability coefficient and histological damage occurrence were thus investigated. Transcranial pulsed FUS at 1.5 MHz in the presence of systemically circulating microbubbles was applied in the mouse hippocampi (n  =  60). The stable and inertial cavitation activities were monitored during sonication. Contrast-enhanced MRI was performed immediately after sonication and every 24 h up to 6 d thereafter, to assess BBB opening, brain tissue permeability and potential edema. Histological evaluations were used to assess the occurrence of neurovascular damages. It was found that stable cavitation was well correlated with: (1) the duration of the BBB opening (r 2   =  0.77); (2) the permeability of the opened BBB (r 2   =  0.82); (3) the likelihood of safe opening (P  <  0.05, safe opening compared to cases of damage; P  <  0.0001, no opening compared to safe opening). The inertial cavitation dose was correlated with the resulting BBB permeability (r 2   =  0.72). Stable cavitation was found to be more reliable than inertial cavitation at assessing the BBB opening within the pressure range used in this study. This study demonstrates that the stable cavitation response during BBB opening holds promise for predicting and controlling the restoration and pharmacokinetics of FUS-opened BBB. The stable cavitation response

  13. Acoustic cavitation-based monitoring of the reversibility and permeability of ultrasound-induced blood-brain barrier opening

    Science.gov (United States)

    Sun, Tao; Samiotaki, Gesthimani; Wang, Shutao; Acosta, Camilo; Chen, Cherry C.; Konofagou, Elisa E.

    2015-12-01

    Cavitation events seeded by microbubbles have been previously reported to be associated with MR- or fluorescent-contrast enhancement after focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening. However, it is still unknown whether bubble activity can be correlated with the reversibility (the duration of opening and the likelihood of safe reinstatement) and the permeability of opened BBB, which is critical for the clinical translation of using passive cavitation detection to monitor, predict and control the opening. In this study, the dependence of acoustic cavitation on the BBB opening duration, permeability coefficient and histological damage occurrence were thus investigated. Transcranial pulsed FUS at 1.5 MHz in the presence of systemically circulating microbubbles was applied in the mouse hippocampi (n  =  60). The stable and inertial cavitation activities were monitored during sonication. Contrast-enhanced MRI was performed immediately after sonication and every 24 h up to 6 d thereafter, to assess BBB opening, brain tissue permeability and potential edema. Histological evaluations were used to assess the occurrence of neurovascular damages. It was found that stable cavitation was well correlated with: (1) the duration of the BBB opening (r2  =  0.77) (2) the permeability of the opened BBB (r2  =  0.82) (3) the likelihood of safe opening (P  cases of damage; P  <  0.0001, no opening compared to safe opening). The inertial cavitation dose was correlated with the resulting BBB permeability (r2  =  0.72). Stable cavitation was found to be more reliable than inertial cavitation at assessing the BBB opening within the pressure range used in this study. This study demonstrates that the stable cavitation response during BBB opening holds promise for predicting and controlling the restoration and pharmacokinetics of FUS-opened BBB. The stable cavitation response therefore showed great promise in predicting the

  14. Genetics Home Reference: Opitz G/BBB syndrome

    Science.gov (United States)

    ... A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Rarely, Opitz G/BBB syndrome is inherited in an autosomal dominant pattern , which means one copy of the altered ...

  15. The bubble-dependent mechanism of FUS-induced blood-brain barrier opening in mice and in monkeys in vivo

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    Tung, Yao-Sheng; Marquet, Fabrice; Vlachos, Fotios; Feshitan, Jameel A.; Borden, Mark A.; Konofagou, Elisa E.

    2012-10-01

    The blood-brain barrier (BBB) prevents most neurological drugs from traversing from the cerebral microvasculature into the brain parenchyma. Previous studies have shown that the presence of bubbles in an acoustic field temporarily opens the BBB. The BBB opening pressure threshold was previously identified to lie between 0.30 and 0.46 MPa in the case of the smaller bubbles and between 0.15 and 0.30 MPa in the larger bubble case. However, the physical effects responsible for BBB opening remain unknown. In addition, the noninvasive in vivo cavitation detection with mono-dispersed microbubbles has not been studied as of yet. The purpose of this study is to unveil the physical mechanism of the FUS-induced BBB opening with monodispersed microbubbles. Lipid-shelled microbubbles with three different diameters (1-2, 4-5 and 6-8 μm) were manufactured in-house and size-isolated using differential centrifugation. Sixty-seven (n=67) mice were each injected intravenously with bubbles of either 1-2, 4-5 or 6-8 μm in diameter and the concentration of 107 numbers/mL. The right hippocampus of each mouse was then sonicated using focused ultrasound (1.5 MHz frequency; 100 cycles (67 μs) pulse length; 10 Hz pulse repetition frequency; 1 minute sonication duration) while the left hippocampus served as the control. A 10-MHz transducer was used as a passive cavitation detector (PCD) to determine the threshold of inertial cavitation (IC). Each mouse was sonicated at a specific acoustic peak-rarefactional pressure at 0.15, 0.30, 0.45 or 0.60 MPa in order to identify the threshold of BBB opening and IC. T1-weighted MRI was used to verify the BBB opening and spectrograms were generated in order to detect the IC onset and duration. Our results suggest that the BBB opens as a result of nonlinear (harmonic) bubble oscillation when the bubble diameter is similar to the capillary diameter and with inertial cavitation when it is not. The bubble may thus have to be in contact with the capillary

  16. An X-ray BBB Michelson interferometer.

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    Sutter, John P; Ishikawa, Tetsuya; Kuetgens, Ulrich; Materlik, Gerhard; Nishino, Yoshinori; Rostomyan, Armen; Tamasaku, Kenji; Yabashi, Makina

    2004-09-01

    A new X-ray Michelson interferometer based on the BBB interferometer of Bonse and Hart and designed for X-rays of wavelength approximately 1 A was described in a previous paper. Here, a further test carried out at the SPring-8 1 km beamline BL29XUL is reported. One of the BBB's mirrors was displaced by a piezo to introduce the required path-length difference. The resulting variation of intensity with piezo voltage as measured by an avalanche photodiode could be ascribed to the phase variation resulting from the path-length change, with a small additional contribution from the change of the position of the lattice planes of the front mirror relative to the rest of the crystal. This 'Michelson fringe' interpretation is supported by the observed steady movement across the output beam of the interference fringes produced by a refractive wedge when the piezo voltage was ramped. The front-mirror displacement required for one complete fringe at the given wavelength is only 0.675 A; therefore, a quiet environment is vital for operating this device, as previous experiments have shown.

  17. Power cavitation-guided blood-brain barrier opening with focused ultrasound and microbubbles

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    Burgess, M. T.; Apostolakis, I.; Konofagou, E. E.

    2018-03-01

    Image-guided monitoring of microbubble-based focused ultrasound (FUS) therapies relies on the accurate localization of FUS-stimulated microbubble activity (i.e. acoustic cavitation). Passive cavitation imaging with ultrasound arrays can achieve this, but with insufficient spatial resolution. In this study, we address this limitation and perform high-resolution monitoring of acoustic cavitation-mediated blood-brain barrier (BBB) opening with a new technique called power cavitation imaging. By synchronizing the FUS transmit and passive receive acquisition, high-resolution passive cavitation imaging was achieved by using delay and sum beamforming with absolute time delays. Since the axial image resolution is now dependent on the duration of the received acoustic cavitation emission, short pulses of FUS were used to limit its duration. Image sets were acquired at high-frame rates for calculation of power cavitation images analogous to power Doppler imaging. Power cavitation imaging displays the mean intensity of acoustic cavitation over time and was correlated with areas of acoustic cavitation-induced BBB opening. Power cavitation-guided BBB opening with FUS could constitute a standalone system that may not require MRI guidance during the procedure. The same technique can be used for other acoustic cavitation-based FUS therapies, for both safety and guidance.

  18. Targeted drug delivery with focused ultrasound-induced blood-brain barrier opening using acoustically-activated nanodroplets.

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    Chen, Cherry C; Sheeran, Paul S; Wu, Shih-Ying; Olumolade, Oluyemi O; Dayton, Paul A; Konofagou, Elisa E

    2013-12-28

    Focused ultrasound (FUS) in the presence of systemically administered microbubbles has been shown to locally, transiently and reversibly increase the permeability of the blood-brain barrier (BBB), thus allowing targeted delivery of therapeutic agents in the brain for the treatment of central nervous system diseases. Currently, microbubbles are the only agents that have been used to facilitate the FUS-induced BBB opening. However, they are constrained within the intravascular space due to their micron-size diameters, limiting the delivery effect at or near the microvessels. In the present study, acoustically-activated nanodroplets were used as a new class of contrast agents to mediate FUS-induced BBB opening in order to study the feasibility of utilizing these nanoscale phase-shift particles for targeted drug delivery in the brain. Significant dextran delivery was achieved in the mouse hippocampus using nanodroplets at clinically relevant pressures. Passive cavitation detection was used in the attempt to establish a correlation between the amount of dextran delivered in the brain and the acoustic emission recorded during sonication. Conventional microbubbles with the same lipid shell composition and perfluorobutane core as the nanodroplets were also used to compare the efficiency of an FUS-induced dextran delivery. It was found that nanodroplets had a higher BBB opening pressure threshold but a lower stable cavitation threshold than microbubbles, suggesting that contrast agent-dependent acoustic emission monitoring was needed. A more homogeneous dextran delivery within the targeted hippocampus was achieved using nanodroplets without inducing inertial cavitation or compromising safety. Our results offered a new means of developing the FUS-induced BBB opening technology for potential extravascular targeted drug delivery in the brain, extending the potential drug delivery region beyond the cerebral vasculature. © 2013.

  19. Examination of Blood-Brain Barrier (BBB) Integrity In A Mouse Brain Tumor Model

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    On, Ngoc; Mitchell, Ryan; Savant, Sanjot D.; Bachmeier, Corbin. J.; Hatch, Grant M.; Miller, Donald W.

    2013-01-01

    The present study evaluates, both functionally and biochemically, brain tumor-induced alterations in brain capillary endothelial cells. Brain tumors were induced in Balb/c mice via intracranial injection of Lewis Lung carcinoma (3LL) cells into the right hemisphere of the mouse brain using stereotaxic apparatus. Blood-brain barrier (BBB) permeability was assessed at various stages of tumor development, using both radiolabeled tracer permeability and magnetic resonance imaging (MRI) with gadolinium diethylene-triamine-pentaacetate contrast enhancement (Gad-DTPA). The expression of the drug efflux transporter, P-glycoprotein (P-gp), in the BBB at various stages of tumor development was also evaluated by Western blot and immunohistochemistry. Median mouse survival following tumor cell injection was 17 days. The permeability of the BBB to 3H-mannitol was similar in both brain hemispheres at 7 and 10 days post-injection. By day 15, there was a 2-fold increase in 3H-mannitol permeability in the tumor bearing hemispheres compared to the non-tumor hemispheres. Examination of BBB permeability with Gad-DTPA contrast enhanced MRI indicated cerebral vascular permeability changes were confined to the tumor area. The permeability increase observed at the later stages of tumor development correlated with an increase in cerebral vascular volume suggesting angiogenesis within the tumor bearing hemisphere. Furthermore, the Gad-DPTA enhancement observed within the tumor area was significantly less than Gad-DPTA enhancement within the circumventricular organs not protected by the BBB. Expression of P-gp in both the tumor bearing and non-tumor bearing portions of the brain appeared similar at all time points examined. These studies suggest that although BBB integrity is altered within the tumor site at later stages of development, the BBB is still functional and limiting in terms of solute and drug permeability in and around the tumor. PMID:23184143

  20. A polymeric micelle magnetic resonance imaging (MRI) contrast agent reveals blood-brain barrier (BBB) permeability for macromolecules in cerebral ischemia-reperfusion injury.

    Science.gov (United States)

    Shiraishi, Kouichi; Wang, Zuojun; Kokuryo, Daisuke; Aoki, Ichio; Yokoyama, Masayuki

    2017-05-10

    Blood-brain barrier (BBB) opening is a key phenomenon for understanding ischemia-reperfusion injuries that are directly linked to hemorrhagic transformation. The recombinant human tissue-type plasminogen activator (rtPA) increases the risk of symptomatic intracranial hemorrhages. Recent imaging technologies have advanced our understanding of pathological BBB disorders; however, an ongoing challenge in the pre-"rtPA treatment" stage is the task of developing a rigorous method for hemorrhage-risk assessments. Therefore, we examined a novel method for assessment of rtPA-extravasation through a hyper-permeable BBB. To examine the image diagnosis of rtPA-extravasation for a rat transient occlusion-reperfusion model, in this study we used a polymeric micelle MRI contrast-agent (Gd-micelles). Specifically, we used two MRI contrast agents at 1h after reperfusion. Gd-micelles provided very clear contrast images in 15.5±10.3% of the ischemic hemisphere at 30min after i.v. injection, whereas a classic gadolinium chelate MRI contrast agent provided no satisfactorily clear images. The obtained images indicate both the hyper-permeable BBB area for macromolecules and the distribution area of macromolecules in the ischemic hemisphere. Owing to their large molecular weight, Gd-micelles remained in the ischemic hemisphere through the hyper-permeable BBB. Our results indicate the feasibility of a novel clinical diagnosis for evaluating rtPA-related hemorrhage risks. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Focused Ultrasound-Induced Blood-Brain Barrier Opening: Association with Mechanical Index and Cavitation Index Analyzed by Dynamic Contrast-Enhanced Magnetic-Resonance Imaging.

    Science.gov (United States)

    Chu, Po-Chun; Chai, Wen-Yen; Tsai, Chih-Hung; Kang, Shih-Tsung; Yeh, Chih-Kuang; Liu, Hao-Li

    2016-09-15

    Focused ultrasound (FUS) with microbubbles can temporally open the blood-brain barrier (BBB), and the cavitation activities of microbubbles play a key role in the BBB-opening process. Previous attempts used contrast-enhanced magnetic resonance imaging (CE-MRI) to correlate the mechanical index (MI) with the scale of BBB-opening, but MI only partially gauged acoustic activities, and CE-MRI did not fully explore correlations of pharmacodynamic/pharmacokinetic behaviors. Recently, the cavitation index (CI) has been derived to serve as an indicator of microbubble-ultrasound stable cavitation, and may also serve as a valid indicator to gauge the level of FUS-induced BBB opening. This study investigates the feasibility of gauging FUS-induced BBB opened level via the two indexes, MI and CI, through dynamic contrast-enhanced (DCE)-MRI analysis as well as passive cavitation detection (PCD) analysis. Pharmacodynamic/pharmacokinetic parameters derived from DCE-MRI were characterized to identify the scale of FUS-induced BBB opening. Our results demonstrated that DCE-MRI can successfully access pharmacodynamic/pharmacokinetic BBB-opened behavior, and was highly correlated both with MI and CI, implying the feasibility in using these two indices to gauge the scale of FUS-induced BBB opening. The proposed finding may facilitate the design toward using focused ultrasound as a safe and reliable noninvasive CNS drug delivery.

  2. Achados audiológicos e eletrofisiológicos de indivíduos com a síndrome G/BBB Auditory findings and electrophysiologics in individuals with G/BBB syndrome

    Directory of Open Access Journals (Sweden)

    Tatiana Vialôgo Cassab

    2011-12-01

    Full Text Available A síndrome G/BBB é uma condição rara, caracterizada por hipertelorismo, fissura de lábio e palato e hipospádia. Não foram encontrados trabalhos sobre a audição em indivíduos com esta síndrome. OBJETIVO: Investigar a função auditiva em pacientes com síndrome G/BBB quanto à ocorrência ou não de perda auditiva e a condução nervosa auditiva periférica e central. MATERIAL E MÉTODO: Catorze pacientes de 7 a 34 anos, do gênero masculino, com a síndrome G/BBB, foram avaliados por meio de otoscopia, audiometria, timpanometria e potenciais evocados auditivos de tronco encefálico (PEATE. Forma de Estudo: Estudo de série clínico prospectivo. RESULTADOS: Limiares audiométricos normais em 12 (66,7% pacientes da amostra e alterados em dois (33,3%, sendo um com perda condutiva e um neurossensorial. Quanto ao PEATE, foram encontrados: latências absolutas da onda I normais em todos os pacientes, aumento das latências absolutas da onda III e V em dois e seis pacientes respectivamente; latências interpicos I-III, III-V e I-V aumentadas em quatro, três e oito pacientes, respectivamente. CONCLUSÃO: Perdas auditivas periféricas podem ocorrer na síndrome G/BBB. Há evidências de comprometimento das vias auditivas centrais em nível do tronco encefálico. Estudos com exames de imagem são necessários para maior clareza dos achados clínicos.The G/BBB syndrome is a rare condition characterized by hypertelorism, cleft lip and palate, and hypospadias. No studies were found on the hearing of individuals with this syndrome. AIM: To investigate the auditory function in patients with G/BBB syndrome, such as the occurrence of hearing loss, and central and peripheral auditory nerve conduction. METHODS: Fourteen male patients aged 7-34 years with the G/BBB syndrome were assessed by otoscopy, audiometry, tympanometry and evoked auditory brainstem response (ABR. Model: A retrospective clinical series study. RESULTS: Audiometric thresholds were

  3. Platelet activating factor induces transient blood-brain barrier opening to facilitate edaravone penetration into the brain.

    Science.gov (United States)

    Fang, Weirong; Zhang, Rui; Sha, Lan; Lv, Peng; Shang, Erxin; Han, Dan; Wei, Jie; Geng, Xiaohan; Yang, Qichuan; Li, Yunman

    2014-03-01

    The blood-brain barrier (BBB) greatly limits the efficacy of many neuroprotective drugs' delivery to the brain, so improving drug penetration through the BBB has been an important focus of research. Here we report that platelet activating factor (PAF) transiently opened BBB and facilitated neuroprotectant edaravone penetration into the brain. Intravenous infusion with PAF induced a transient BBB opening in rats, reflected by increased Evans blue leakage and mild edema formation, which ceased within 6 h. Furthermore, rat regional cerebral blood flow (rCBF) declined acutely during PAF infusion, but recovered slowly. More importantly, this transient BBB opening significantly increased the penetration of edaravone into the brain, evidenced by increased edaravone concentrations in tissue interstitial fluid collected by microdialysis and analyzed by Ultra-performance liquid chromatograph combined with a hybrid quadrupole time-of-flight mass spectrometer (UPLC-MS/MS). Similarly, incubation of rat brain microvessel endothelial cells monolayer with 1 μM PAF for 1 h significantly increased monolayer permeability to (125)I-albumin, which recovered 1 h after PAF elimination. However, PAF incubation with rat brain microvessel endothelial cells for 1 h did not cause detectable cytotoxicity, and did not regulate intercellular adhesion molecule-1, matrix-metalloproteinase-9 and P-glycoprotein expression. In conclusion, PAF could induce transient and reversible BBB opening through abrupt rCBF decline, which significantly improved edaravone penetration into the brain. Platelet activating factor (PAF) transiently induces BBB dysfunction and increases BBB permeability, which may be due to vessel contraction and a temporary decline of regional cerebral blood flow (rCBF) triggered by PAF. More importantly, the PAF induced transient BBB opening facilitates neuroprotectant edaravone penetration into brain. The results of this study may provide a new approach to improve drug delivery into

  4. Amphiphilic HPMA-LMA copolymers increase the transport of Rhodamine 123 across a BBB model without harming its barrier integrity.

    Science.gov (United States)

    Hemmelmann, Mirjam; Metz, Verena V; Koynov, Kaloian; Blank, Kerstin; Postina, Rolf; Zentel, Rudolf

    2012-10-28

    The successful non-invasive treatment of diseases associated with the central nervous system (CNS) is generally limited by poor brain permeability of various developed drugs. The blood-brain barrier (BBB) prevents the passage of therapeutics to their site of action. Polymeric drug delivery systems are promising solutions to effectively transport drugs into the brain. We recently showed that amphiphilic random copolymers based on the hydrophilic p(N-(2-hydroxypropyl)-methacrylamide), pHPMA, possessing randomly distributed hydrophobic p(laurylmethacrylate), pLMA, are able to mediate delivery of domperidone into the brain of mice in vivo. To gain further insight into structure-property relations, a library of carefully designed polymers based on p(HPMA) and p(LMA) was synthesized and tested applying an in vitro BBB model which consisted of human brain microvascular endothelial cells (HBMEC). Our model drug Rhodamine 123 (Rh123) exhibits, like domperidone, a low brain permeability since both substances are recognized by efflux transporters at the BBB. Transport studies investigating the impact of the polymer architecture in relation to the content of hydrophobic LMA revealed that random p(HPMA)-co-p(LMA) having 10mol% LMA is the most auspicious system. The copolymer significantly increased the permeability of Rh123 across the HBMEC monolayer whereas transcytosis of the polymer was very low. Further investigations on the mechanism of transport showed that integrity and barrier function of the BBB model were not harmed by the polymer. According to our results, p(HPMA)-co-p(LMA) copolymers are a promising delivery system for neurological therapeutics and their application might open alternative treatment strategies. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Quantitative assessment of the blood-brain barrier opening caused by Streptococcus agalactiae hyaluronidase in a BALB/c mouse model.

    Science.gov (United States)

    Luo, Su; Cao, Qing; Ma, Ke; Wang, Zhaofei; Liu, Guangjin; Lu, Chengping; Liu, Yongjie

    2017-10-19

    Streptococcus agalactiae is a pathogen causing meningitis in animals and humans. However, little is known about the entry of S. agalactiae into brain tissue. In this study, we developed a BALB/c mouse model based on the intravenous injection of β-galactosidase-positive Escherichia coli M5 as an indicator of blood-brain barrier (BBB) opening. Under physiological conditions, the BBB is impermeable to E. coli M5. In pathological conditions caused by S. agalactiae, E. coli M5 is capable of penetrating the brain through a disrupted BBB. The level of BBB opening can be assessed by quantitative measurement of E. coli M5 loads per gram of brain tissue. Further, we used the model to evaluate the role of S. agalactiae hyaluronidase in BBB opening. The inactivation of hylB gene encoding a hyaluronidase, HylB, resulted in significantly decreased E. coli M5 colonization, and the intravenous injection of purified HylB protein induced BBB opening in a dose-dependent manner. This finding verified the direct role of HylB in BBB invasion and traversal, and further demonstrated the practicability of the in vivo mouse model established in this study. This model will help to understand the S. agalactiae-host interactions that are involved in this bacterial traversal of the BBB and to develop efficacious strategies to prevent central nervous system infections.

  6. Feasibility study of a single-element transcranial focused ultrasound system for blood-brain barrier opening

    Science.gov (United States)

    Marquet, Fabrice; Tung, Yao-Sheng; Teichert, Tobias; Ferrera, Vincent P.; Konofagou, Elisa E.

    2012-10-01

    The blood-brain barrier (BBB) is a specialized vascular system that impedes entry of all large and the vast majority of small molecules including the most potent CNS disease therapeutic agents from entering from the lumen into the brain parenchyma. Microbubble-enhanced, focused ultrasound (ME-FUS) has been previously shown to disrupt noninvasively, selectively, and transiently the BBB in small animals in vivo. The study addresses the focusing properties of single-element transducers at intermediate frequencies (500 kHz) through primate and human skulls, targeting clinically relevant targets extracted from 3D brain atlases such as the hippocampus and the basal ganglia, which are typically affected by early Alzheimer's and Parkinson's disease, respectively. A preliminary in vivo study was performed to study the frequency dependence of BBB opening parameters in mice. Then, feasibility of transcranial ME-FUS BBB opening in non-human primates was demonstrated with subsequent BBB recovery. Sonications were combined with two different types of microbubbles (custom made 4-5 μm and Definity®). 3T MRI was used to confirm the BBB disruption and to assess brain damage.

  7. In vivo transcranial cavitation threshold detection during ultrasound-induced blood-brain barrier opening in mice

    International Nuclear Information System (INIS)

    Tung, Yao-Sheng; Vlachos, Fotios; Choi, James J; Deffieux, Thomas; Selert, Kirsten; Konofagou, Elisa E

    2010-01-01

    The in vivo cavitation response associated with blood-brain barrier (BBB) opening as induced by transcranial focused ultrasound (FUS) in conjunction with microbubbles was studied in order to better identify the underlying mechanism in its noninvasive application. A cylindrically focused hydrophone, confocal with the FUS transducer, was used as a passive cavitation detector (PCD) to identify the threshold of inertial cavitation (IC) in the presence of Definity (registered) microbubbles (mean diameter range: 1.1-3.3 μm, Lantheus Medical Imaging, MA, USA). A vessel phantom was first used to determine the reliability of the PCD prior to in vivo use. A cerebral blood vessel was simulated by generating a cylindrical channel of 610 μm in diameter inside a polyacrylamide gel and by saturating its volume with microbubbles. The microbubbles were sonicated through an excised mouse skull. Second, the same PCD setup was employed for in vivo noninvasive (i.e. transdermal and transcranial) cavitation detection during BBB opening. After the intravenous administration of Definity (registered) microbubbles, pulsed FUS was applied (frequency: 1.525 or 1.5 MHz, peak-rarefactional pressure: 0.15-0.60 MPa, duty cycle: 20%, PRF: 10 Hz, duration: 1 min with a 30 s interval) to the right hippocampus of twenty-six (n = 26) mice in vivo through intact scalp and skull. T1 and T2-weighted MR images were used to verify the BBB opening. A spectrogram was generated at each pressure in order to detect the IC onset and duration. The threshold of BBB opening was found to be at a 0.30 MPa peak-rarefactional pressure in vivo. Both the phantom and in vivo studies indicated that the IC pressure threshold had a peak-rarefactional amplitude of 0.45 MPa. This indicated that BBB opening may not require IC at or near the threshold. Histological analysis showed that BBB opening could be induced without any cellular damage at 0.30 and 0.45 MPa. In conclusion, the cavitation response could be detected without

  8. In vivo transcranial cavitation threshold detection during ultrasound-induced blood-brain barrier opening in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tung, Yao-Sheng; Vlachos, Fotios; Choi, James J; Deffieux, Thomas; Selert, Kirsten; Konofagou, Elisa E, E-mail: ek2191@columbia.ed [Department of Biomedical Engineering, Columbia University, New York, NY (United States)

    2010-10-21

    The in vivo cavitation response associated with blood-brain barrier (BBB) opening as induced by transcranial focused ultrasound (FUS) in conjunction with microbubbles was studied in order to better identify the underlying mechanism in its noninvasive application. A cylindrically focused hydrophone, confocal with the FUS transducer, was used as a passive cavitation detector (PCD) to identify the threshold of inertial cavitation (IC) in the presence of Definity (registered) microbubbles (mean diameter range: 1.1-3.3 {mu}m, Lantheus Medical Imaging, MA, USA). A vessel phantom was first used to determine the reliability of the PCD prior to in vivo use. A cerebral blood vessel was simulated by generating a cylindrical channel of 610 {mu}m in diameter inside a polyacrylamide gel and by saturating its volume with microbubbles. The microbubbles were sonicated through an excised mouse skull. Second, the same PCD setup was employed for in vivo noninvasive (i.e. transdermal and transcranial) cavitation detection during BBB opening. After the intravenous administration of Definity (registered) microbubbles, pulsed FUS was applied (frequency: 1.525 or 1.5 MHz, peak-rarefactional pressure: 0.15-0.60 MPa, duty cycle: 20%, PRF: 10 Hz, duration: 1 min with a 30 s interval) to the right hippocampus of twenty-six (n = 26) mice in vivo through intact scalp and skull. T1 and T2-weighted MR images were used to verify the BBB opening. A spectrogram was generated at each pressure in order to detect the IC onset and duration. The threshold of BBB opening was found to be at a 0.30 MPa peak-rarefactional pressure in vivo. Both the phantom and in vivo studies indicated that the IC pressure threshold had a peak-rarefactional amplitude of 0.45 MPa. This indicated that BBB opening may not require IC at or near the threshold. Histological analysis showed that BBB opening could be induced without any cellular damage at 0.30 and 0.45 MPa. In conclusion, the cavitation response could be detected

  9. In vivo transcranial cavitation threshold detection during ultrasound-induced blood-brain barrier opening in mice.

    Science.gov (United States)

    Tung, Yao-Sheng; Vlachos, Fotios; Choi, James J; Deffieux, Thomas; Selert, Kirsten; Konofagou, Elisa E

    2010-10-21

    The in vivo cavitation response associated with blood-brain barrier (BBB) opening as induced by transcranial focused ultrasound (FUS) in conjunction with microbubbles was studied in order to better identify the underlying mechanism in its noninvasive application. A cylindrically focused hydrophone, confocal with the FUS transducer, was used as a passive cavitation detector (PCD) to identify the threshold of inertial cavitation (IC) in the presence of Definity® microbubbles (mean diameter range: 1.1-3.3 µm, Lantheus Medical Imaging, MA, USA). A vessel phantom was first used to determine the reliability of the PCD prior to in vivo use. A cerebral blood vessel was simulated by generating a cylindrical channel of 610 µm in diameter inside a polyacrylamide gel and by saturating its volume with microbubbles. The microbubbles were sonicated through an excised mouse skull. Second, the same PCD setup was employed for in vivo noninvasive (i.e. transdermal and transcranial) cavitation detection during BBB opening. After the intravenous administration of Definity® microbubbles, pulsed FUS was applied (frequency: 1.525 or 1.5 MHz, peak-rarefactional pressure: 0.15-0.60 MPa, duty cycle: 20%, PRF: 10 Hz, duration: 1 min with a 30 s interval) to the right hippocampus of twenty-six (n = 26) mice in vivo through intact scalp and skull. T1 and T2-weighted MR images were used to verify the BBB opening. A spectrogram was generated at each pressure in order to detect the IC onset and duration. The threshold of BBB opening was found to be at a 0.30 MPa peak-rarefactional pressure in vivo. Both the phantom and in vivo studies indicated that the IC pressure threshold had a peak-rarefactional amplitude of 0.45 MPa. This indicated that BBB opening may not require IC at or near the threshold. Histological analysis showed that BBB opening could be induced without any cellular damage at 0.30 and 0.45 MPa. In conclusion, the cavitation response could be detected without craniotomy in mice

  10. Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling.

    Science.gov (United States)

    Liu, Xiaobai; Wang, Zhenhua; Wang, Ping; Yu, Bo; Liu, Yunhui; Xue, Yixue

    2013-07-21

    It has been supposed that green tea polyphenols (GTPs) have neuroprotective effects on brain damage after brain ischemia in animal experiments. Little is known regarding GTPs' protective effects against the blood-brain barrier (BBB) disruption after ischemic stroke. We investigated the effects of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding cellular mechanisms involved in the early stage of cerebral ischemia. Male Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for 0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by intragastric gavage twice a day for 30 days prior to MCAO. At different time points, the expression of claudin-5, occludin, ZO-1, and PKCα signaling pathway in microvessel fragments of cerebral ischemic tissue were evaluated. GTPs reduced BBB permeability at 60 min and 120 min after ischemia as compared with the vehicle group. Transmission electron microscopy also revealed that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and 120 min after MACO. The decreased mRNA and protein expression levels of claudin-5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were significantly prevented by treatment with GTPs at the same time points after ischemia in rats. Furthermore, GTPs could attenuate the increase in the expression levels of PKCα mRNA and protein caused by cerebral ischemia. These results demonstrate that GTPs may act as a potential neuroprotective agent against BBB damage at the early stage of focal cerebral ischemia through the regulation of TJ and PKCα signaling.

  11. Multi-modality safety assessment of blood-brain barrier opening using focused ultrasound and definity microbubbles: a short-term study.

    Science.gov (United States)

    Baseri, Babak; Choi, James J; Tung, Yao-Sheng; Konofagou, Elisa E

    2010-09-01

    As a potentially viable method of brain drug delivery, the safety profile of blood-brain barrier (BBB) opening using focused ultrasound (FUS) and ultrasound contrast agents (UCA) needs to be established. In this study, we provide a short-term (30-min or 5-h survival) histological assessment of murine brains undergoing FUS-induced BBB opening. Forty-nine mice were intravenously injected with Definity microbubbles (0.05 microL/kg) and sonicated under the following parameters: frequency of 1.525 MHz, pulse length of 20 ms, pulse repetition frequency of 10 Hz, peak rarefactional acoustic pressures of 0.15-0.98 MPa and two 30-s sonication intervals with an intermittent 30-s delay. The BBB opening threshold was found to be 0.15-0.3 MPa based on fluorescence and magnetic resonance imaging of systemically injected tracers. Analysis of three histological measures in hematoxylin and eosin-stained sections revealed the safest acoustic pressure to be within the range of 0.3-0.46 MPa in all examined time periods post sonication. Across different pressure amplitudes, only the samples 30 min post opening showed significant difference (p < 0.05) in the average number of distinct damaged sites, microvacuolated sites, dark neurons and sites with extravasated erythrocytes. Enhanced fluorescence around severed microvessels was also noted and found to be associated with the largest tissue effects, whereas mildly diffuse BBB opening with uniform fluorescence in the parenchyma was associated with no or mild tissue injury. Region-specific areas of the sonicated brain (thalamus, hippocampal fissure, dentate gyrus and CA3 area of hippocampus) exhibited variation in fluorescence intensity based on the position, orientation and size of affected vessels. The results of this short-term histological analysis demonstrated the feasibility of a safe FUS-UCA-induced BBB opening under a specific set of sonication parameters and provided new insights on the mechanism of BBB opening.

  12. Blood-brain barrier (BBB) toxicity and permeability assessment after L-(4-¹⁰Boronophenyl)alanine, a conventional B-containing drug for boron neutron capture therapy, using an in vitro BBB model.

    Science.gov (United States)

    Roda, E; Nion, S; Bernocchi, G; Coccini, T

    2014-10-02

    Since brain tumours are the primary candidates for treatment by Boron Neutron Capture Therapy, one major challenge in the selective drug delivery to CNS is the crossing of the blood-brain barrier (BBB). The present pilot study investigated (i) the transport of a conventional B-containing product (i.e., L-(4-(10)Boronophenyl)alanine, L-(10)BPA), already used in medicine but still not fully characterized regarding its CNS interactions, as well as (ii) the effects of the L-(10)BPA on the BBB integrity using an in vitro model, consisting of brain capillary endothelial cells co-cultured with glial cells, closely mimicking the in vivo conditions. The multi-step experimental strategy (i.e. Integrity test, Filter study, Transport assay) checked L-(10)BPA toxicity at 80 µg Boron equivalent/ml, and its ability to cross the BBB, additionally by characterizing the cytoskeletal and TJ's proteins by immunocytochemistry and immunoblotting. In conclusion, a lack of toxic effects of L-(10)BPA was demonstrated, nevertheless accompanied by cellular stress phenomena (e.g. vimentin expression modification), paralleled by a low permeability coefficient (0.39 ± 0.01 × 10(-3)cm min(-1)), corroborating the scarce probability that L-(10)BPA would reach therapeutically effective cerebral concentration. These findings emphasized the need for novel strategies aimed at optimizing boron delivery to brain tumours, trying to ameliorate the compound uptake or developing new targeted products suitable to safely and effectively treat head cancer. Thus, the use of in vitro BBB model for screening studies may provide a useful early safety assessment for new effective compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Development, Characterization, and Implementation of a System for Focused Ultrasound-Mediated Blood-Brain Barrier Opening in Mice

    Science.gov (United States)

    Valdez, Michael Aaron

    The blood-brain barrier BBB refers to the set of specialized endothelial cells that line the vasculature in the brain and effectively control movement of molecules into and out of the brain. While necessary for proper brain function, the BBB blocks 98% of drugs from entering the brain and is the most significant barrier to developing therapies for neurodegenerative diseases. Active transport allows some specific molecules to cross the BBB, but therapeutic development using this route has had limited success. A number of techniques have been used to bypass the BBB, but are often highly invasive and ineffective. Over the last two decades, a minimally invasive technique to transiently open the BBB has been under development that utilizes transcranial focused ultrasound (FUS) in combination with intravascular microbubble contrast agents. This method is often carried out in conjunction with magnetic resonance imaging (MRI) to guide and assess BBB opening and has been referred to as MRI guided FUS (MRgFUS). Because of the utility of mouse models of neurological disease and the exploratory nature of MRgFUS, systems that allow BBB opening in mice are a useful and necessary tool to develop and evaluate this method for clinical application. In this dissertation project, a custom built, cost-effective FUS system for opening the BBB in mice was developed, with the objective of using this device to deliver therapeutics to the brain. Being a custom device, it was necessary to evaluate the ultrasound output, verify in vivo safety, and anticipate the therapeutic effect. The scope of the work herein consists of the design, construction, and evaluation of system that fulfills these requirements. The final constructed system cost was an order of magnitude less than any commercially available MRgFUS system. At this low price point, the hardware could allow the implementation of the methodology in many more research areas than previously possible. Additionally, to anticipate the

  14. Simultaneous estimations of blood brain barrier (BBB) permeability and local cerebral blood volume (CBV) in human brain tumors with positron tomography and Ga-68 EDTA

    International Nuclear Information System (INIS)

    Hawkins, R.A.; Phelps, M.E.; Huang, S.C.; Wapenski, J.A.; Grimm, P.D.; Greenberg, P.; Parker, R.G.; Juillard, G.; Kuhl, D.E.

    1984-01-01

    Using Ga-68 EDTA and a two compartment model for diffusion across the BBB that includes a weighted subtraction term for determination of the relative CBV (compared to a normal region of brain with an intact BBB) or the absolute value of CBV (using measurements of Ga-68 concentrations in the blood: the input function), the authors determined values for the forward and reverse rate constants (k1 and k2) for diffusion across the BBB as well as values of CBV in 12 subjects with primary or metastatic brain tumors. Patients were studied on a NeuroECAT tomograph; imaging times were 1 to 10 minutes per scan for a total of about 2 hours. Measurements of Ga-68 concentrations were made on plasma arterial samples. Four direct measurements (in 3 subjects) of CBV using C(15-0) were also obtained. Values of k1 (the transfer constant which numerically approximates the capillary permeability surface area (PS) product) averaged 0.0030 (+- 0.0017) ml/min/gm while k2 averaged 0.0308 (+- 0.0157)/min. Linear regression analysis of the relative CBV in 7 tumor deposits in 4 paired Ga-68 EDTA/C(15-0) studies compared to normal brain tissues resulted in a correlation coefficient of 0.97 for the two methods. The estimates of k1 and k2 were insensitive to changes in the location of the control regions (although CBV estimates changed appropriately) as well as to substituting the input function for a normal brain region when determining the absolute CBV of the lesions

  15. An Open Localization and Local Communication Embodied Sensor

    Directory of Open Access Journals (Sweden)

    Alvaro Gutiérrez

    2008-11-01

    Full Text Available In this paper we describe a localization and local communication system which allows situated agents to communicate locally, obtaining at the same time both the range and the bearing of the emitter without the need of any centralized control or any external reference. The system relies on infrared communications with frequency modulation and is composed of two interconnected modules for data and power measurement. Thanks to the open hardware license under which it is released, the research community can easily replicate the system at a low cost and/or adapt it for applications in sensor networks and in robotics.

  16. Blood-Brain Barrier Opening in Behaving Non-Human Primates via Focused Ultrasound with Systemically Administered Microbubbles

    Science.gov (United States)

    Downs, Matthew E.; Buch, Amanda; Karakatsani, Maria Eleni; Konofagou, Elisa E.; Ferrera, Vincent P.

    2015-10-01

    Over the past fifteen years, focused ultrasound coupled with intravenously administered microbubbles (FUS) has been proven an effective, non-invasive technique to open the blood-brain barrier (BBB) in vivo. Here we show that FUS can safely and effectively open the BBB at the basal ganglia and thalamus in alert non-human primates (NHP) while they perform a behavioral task. The BBB was successfully opened in 89% of cases at the targeted brain regions of alert NHP with an average volume of opening 28% larger than prior anesthetized FUS procedures. Safety (lack of edema or microhemorrhage) of FUS was also improved during alert compared to anesthetized procedures. No physiological effects (change in heart rate, motor evoked potentials) were observed during any of the procedures. Furthermore, the application of FUS did not disrupt reaching behavior, but in fact improved performance by decreasing reaction times by 23 ms, and significantly decreasing touch error by 0.76 mm on average.

  17. Public demand for preserving local open space.

    Science.gov (United States)

    Jeffrey D. Kline

    2006-01-01

    Increased development results in the loss of forest, farm, range, and other open space lands that contribute to the quality of life of U.S. residents. I describe an economic rationale for growing public support for preserving local open space, based the growing scarcity of open space lands. I test the rationale empirically by correlating the prevalence of open space...

  18. Application of optical coherence tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood-brain barrier: mechanisms of brain clearing

    Science.gov (United States)

    Semyachkina-Glushkovskaya, Oxana; Abdurashitov, Arkady; Dubrovsky, Alexander; Bragin, Denis; Bragina, Olga; Shushunova, Nataliya; Maslyakova, Galina; Navolokin, Nikita; Bucharskaya, Alla; Tuchin, Valery; Kurths, Juergen; Shirokov, Alexander

    2017-12-01

    The meningeal lymphatic vessels were discovered 2 years ago as the drainage system involved in the mechanisms underlying the clearance of waste products from the brain. The blood-brain barrier (BBB) is a gatekeeper that strongly controls the movement of different molecules from the blood into the brain. We know the scenarios during the opening of the BBB, but there is extremely limited information on how the brain clears the substances that cross the BBB. Here, using the model of sound-induced opening of the BBB, we clearly show how the brain clears dextran after it crosses the BBB via the meningeal lymphatic vessels. We first demonstrate successful application of optical coherence tomography (OCT) for imaging of the lymphatic vessels in the meninges after opening of the BBB, which might be a new useful strategy for noninvasive analysis of lymphatic drainage in daily clinical practice. Also, we give information about the depth and size of the meningeal lymphatic vessels in mice. These new fundamental data with the applied focus on the OCT shed light on the mechanisms of brain clearance and the role of lymphatic drainage in these processes that could serve as an informative platform for a development of therapy and diagnostics of diseases associated with injuries of the BBB such as stroke, brain trauma, glioma, depression, or Alzheimer disease.

  19. The role of multidrug resistance protein (MRP-1) as an active efflux transporter on blood-brain barrier (BBB) permeability.

    Science.gov (United States)

    Lingineni, Karthik; Belekar, Vilas; Tangadpalliwar, Sujit R; Garg, Prabha

    2017-05-01

    Drugs acting on central nervous system (CNS) may take longer duration to reach the market as these compounds have a higher attrition rate in clinical trials due to the complexity of the brain, side effects, and poor blood-brain barrier (BBB) permeability compared to non-CNS-acting compounds. The roles of active efflux transporters with BBB are still unclear. The aim of the present work was to develop a predictive model for BBB permeability that includes the MRP-1 transporter, which is considered as an active efflux transporter. A support vector machine model was developed for the classification of MRP-1 substrates and non-substrates, which was validated with an external data set and Y-randomization method. An artificial neural network model has been developed to evaluate the role of MRP-1 on BBB permeation. A total of nine descriptors were selected, which included molecular weight, topological polar surface area, ClogP, number of hydrogen bond donors, number of hydrogen bond acceptors, number of rotatable bonds, P-gp, BCRP, and MRP-1 substrate probabilities for model development. We identified 5 molecules that fulfilled all criteria required for passive permeation of BBB, but they all have a low logBB value, which suggested that the molecules were effluxed by the MRP-1 transporter.

  20. Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction.

    Science.gov (United States)

    Xu, Yali; Cui, Hai; Zhu, Qiong; Hua, Xing; Xia, Hongmei; Tan, Kaibin; Gao, Yunhua; Zhao, Jing; Liu, Zheng

    2016-01-01

    Objective. Blood-brain barrier (BBB) is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p ultrasound-exposed hemisphere (4 ± 1, grade 2) while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

  1. Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction

    Directory of Open Access Journals (Sweden)

    Yali Xu

    2016-01-01

    Full Text Available Objective. Blood-brain barrier (BBB is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p<0.01. Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4±1, grade 2 while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

  2. Novel Therapeutic Effects of Leonurine On Ischemic Stroke: New Mechanisms of BBB Integrity

    Directory of Open Access Journals (Sweden)

    Qiu-Yan Zhang

    2017-01-01

    Full Text Available Stroke is a leading cause of morbidity and mortality globally. Leonurine (also named SCM-198, a compound extracted from Herba leonuri, was effective on the prevention of various cardiovascular and brain diseases. The purpose of this study was to explore the possible therapeutic potential of SCM-198 against ischemia reperfusion injury and underlying mechanisms. In the in vivo transient middle cerebral artery occlusion (tMCAO rat model, we found that treatment with SCM-198 could decrease infarct volume and improve neurological deficit by protecting against blood-brain barrier (BBB breakdown. In the in vitro model of cell oxygen-glucose deprivation and reoxygenation (OGD/R, consistent results were obtained with decreased reactive oxygen species (ROS production and maintained the BBB integrity. Further study demonstrated that SCM-198 increased the expression of histone deacetylase- (HDAC- 4 which could inhibit NADPH oxidase- (NOX- 4 and matrix metalloproteinase- (MMP- 9 expression, resulting in the elevation of tight junction proteins, including claudin-5, occludin, and zonula occluden- (ZO- 1. These results indicated SCM-198 protected BBB integrity by regulating the HDAC4/NOX4/MMP-9 tight junction pathway. Our findings provided novel insights into the protective effects and mechanisms of SCM-198 on ischemic stroke, indicating SCM-198 as a new class of potential drug against acute onset of ischemic stroke.

  3. Real-time, transcranial monitoring of safe blood-brain barrier opening in non-human primates.

    Directory of Open Access Journals (Sweden)

    Fabrice Marquet

    Full Text Available The delivery of drugs to specific neural targets faces two fundamental problems: (1 most drugs do not cross the blood-brain barrier, and (2 those that do, spread to the entire brain. To date, there exists only one non-invasive methodology with the potential to solve these problems: selective blood-brain barrier (BBB opening using micro-bubble enhanced focused ultrasound. We have recently developed a single-element 500-kHz spherical transducer ultrasound setup for targeted BBB opening in the non-human primate that does not require simultaneous MRI monitoring. So far, however, the targeting accuracy that can be achieved with this system has not been quantified systematically. In this paper, the accuracy of this system was tested by targeting caudate nucleus and putamen of the basal ganglia in two macaque monkeys. The average lateral targeting error of the system was ∼2.5 mm while the axial targeting error, i.e., along the ultrasound path, was ∼1.5 mm. We have also developed a real-time treatment monitoring technique based on cavitation spectral analysis. This technique also allowed for delineation of a safe and reliable acoustic parameter window for BBB opening. In summary, the targeting accuracy of the system was deemed to be suitable to reliably open the BBB in specific sub-structures of the basal ganglia even in the absence of MRI-based verification of opening volume and position. This establishes the method and the system as a potentially highly useful tool for brain drug delivery.

  4. Opening of brain blood barrier induced by red light and central analgesic improvement of cobra neurotoxin.

    Science.gov (United States)

    Ye, Yong; Li, Yue; Fang, Fei

    2014-05-05

    Cobra neurotoxin (NT) has central analgesic effects, but it is difficult to pass through brain blood barrier (BBB). A novel method of red light induction is designed to help NT across BBB, which is based on photosensitizer activation by red light to generate reactive oxygen species (ROS) to open BBB. The effects were evaluated on cell models and animals in vivo with illumination by semiconductor laser at 670nm on photosensitizer pheophorbide isolated from silkworm excrement. Brain microvascular endothelial cells and astrocytes were co-cultured to build up BBB cell model. The radioactivity of (125)I-NT was measured in cells and tissues for NT permeation. Three ways of cranial irradiation, nasal cavity and intravascular irradiation were tested with combined injection of (125)I-NT 20μg/kg and pheophorbide 100μg/kg to rats, and organs of rats were separated and determined the radioactivity. Paw pressure test in rats, hot plate and writhing test in mice were applied to appraise the analgesic effects. NT across BBB cell model increased with time of illumination, and reached stable level after 60min. So did ROS in cells. NT mainly distributed in liver and kidney of rats, significantly increased in brain after illumination, and improved analgesic effects. Excitation of pheophorbide at red light produces ROS to open BBB, help NT enter brain, and enhance its central action. This research provides a new method for drug across BBB to improve its central role. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. P-glycoprotein mediated efflux limits the transport of the novel anti-Parkinson's disease candidate drug FLZ across the physiological and PD pathological in vitro BBB models.

    Directory of Open Access Journals (Sweden)

    Qian Liu

    Full Text Available FLZ, a novel anti-Parkinson's disease (PD candidate drug, has shown poor blood-brain barrier (BBB penetration based on the pharmacokinetic study using rat brain. P-glycoprotein (P-gp and breast cancer resistance protein (BCRP are two important transporters obstructing substrates entry into the CNS as well as in relation to PD neuropathology. However, it is unclear whether P-gp and BCRP are involved in low BBB permeability of FLZ and what the differences of FLZ brain penetration are between normal and Parkinson's conditions. For this purpose, in vitro BBB models mimicking physiological and PD pathological-related BBB properties were constructed by C6 astroglial cells co-cultured with primary normal or PD rat cerebral microvessel endothelial cells (rCMECs and in vitro permeability experiments of FLZ were carried out. High transepithelial electrical resistance (TEER and low permeability for sodium fluorescein (NaF confirmed the BBB functionality of the two models. Significantly greater expressions of P-gp and BCRP were detected in PD rCMECs associated with the lower in vitro BBB permeability of FLZ in pathological BBB model compared with physiological model. In transport studies only P-gp blocker effectively inhibited the efflux of FLZ, which was consistent with the in vivo permeability data. This result was also confirmed by ATPase assays, suggesting FLZ is a substrate for P-gp but not BCRP. The present study first established in vitro BBB models reproducing PD-related changes of BBB functions in vivo and demonstrated that poor brain penetration of FLZ and low BBB permeability were due to the P-gp transport.

  6. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces edema due to BBB disruption induced by MMP-9 activation in rat hippocampus.

    Science.gov (United States)

    Pérez-Hernández, Mercedes; Fernández-Valle, María Encarnación; Rubio-Araiz, Ana; Vidal, Rebeca; Gutiérrez-López, María Dolores; O'Shea, Esther; Colado, María Isabel

    2017-05-15

    The recreational drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier (BBB) integrity in rats through an early P2X 7 receptor-mediated event which induces MMP-9 activity. Increased BBB permeability often causes plasma proteins and water to access cerebral tissue leading to vasogenic edema formation. The current study was performed to examine the effect of a single neurotoxic dose of MDMA (12.5 mg/kg, i.p.) on in vivo edema development associated with changes in the expression of the perivascular astrocytic water channel, AQP4, as well as in the expression of the tight-junction (TJ) protein, claudin-5 and Evans Blue dye extravasation in the hippocampus of adult male Dark Agouti rats. We also evaluated the ability of the MMP-9 inhibitor, SB-3CT (25 mg/kg, i.p.), to prevent these changes in order to validate the involvement of MMP-9 activation in MDMA-induced BBB disruption. The results show that MDMA produces edema of short duration temporally associated with changes in AQP4 expression and a reduction in claudin-5 expression, changes which are prevented by SB-3CT. In addition, MDMA induces a short-term increase in both tPA activity and expression, a serine-protease which is involved in BBB disruption and upregulation of MMP-9 expression. In conclusion, this study provides evidence enough to conclude that MDMA induces edema of short duration due to BBB disruption mediated by MMP-9 activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Liposomes and lipid disks traverse the BBB and BBTB as intact forms as revealed by two-step Förster resonance energy transfer imaging

    Directory of Open Access Journals (Sweden)

    Tongcheng Dai

    2018-03-01

    Full Text Available The blood–brain barrier (BBB and the blood–brain tumor barrier (BBTB prevent drug and nano-drug delivery systems from entering the brain. However, ligand-mediated nano-drug delivery systems have significantly enhanced the therapeutic treatment of glioma. In this study we investigated the mechanism especially the integrity of liposomes and lipid disks while traversing the BBB and BBTB both in vitro and in vivo. Fluorophores (DiO, DiI and DiD were loaded into liposomes and lipid disks to form Förster resonance energy transfer (FRET nano-drug delivery systems. Using brain capillary endothelial cells as a BBB model, we show that liposomes and disks are present in the cytoplasm as their intact forms and traverse the BBB with a ratio of 0.68‰ and 1.67‰, respectively. Using human umbilical vein endothelial cells as BBTB model, liposomes and disks remained intact and traversed the BBTB with a ratio of 2.31‰ and 8.32‰ at 3 h. Ex vivo imaging and immunohistochemical results revealed that liposomes and disks could traverse the BBB and BBTB in vivo as intact forms. In conclusion, these observations explain in part the mechanism by which nano-drug delivery systems increase the therapeutic treatment of glioma. KEY WORDS: Liposomes, Disks, Intact form, BBB, BBTB, FRET

  8. Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging.

    Science.gov (United States)

    Liao, Ai-Ho; Liu, Hao-Li; Su, Chia-Hao; Hua, Mu-Yi; Yang, Hung-Wei; Weng, Yu-Ting; Hsu, Po-Hung; Huang, Sheng-Min; Wu, Shih-Yen; Wang, Hsin-Ell; Yen, Tzu-Chen; Li, Pai-Chi

    2012-05-07

    This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×10(9) MBs ml(-1) using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C(3)F(8)) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd(3+) ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T(1)-weighted turbo-spin-echo sequence MR imaging. Heavy T(2)*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T(1)-, T(2)- and T(2)*-weighted MR images. The r(1) and r(2) relaxivities for Gd-DTPA were 7.69 and 21.35 s(-1)mM(-1), respectively, indicating that the MBs represent a positive contrast agent in T(1)-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual

  9. Noninvasive, localized, and transient brain drug delivery using focused ultrasound and microbubbles

    Science.gov (United States)

    Choi, James J.

    In the United States, Alzheimer's disease (AD), Parkinson's disease (PD), and brain cancer caused 72,432, 19,566 and 12,886 deaths in 2006, respectively. Whereas the number of deaths due to major disorders such as heart disease, stroke, and prostate cancer have decreased since 2006, deaths attributed to AD, PD, and brain cancer have not. Treatment options for patients with CNS disorders remain limited despite significant advances in knowledge of CNS disease pathways and development of neurologically potent agents. One of the major obstacles is that the cerebral microvasculature is lined by a specialized and highly regulated blood-brain barrier (BBB) that prevents large agents from entering the brain extracellular space. The purpose of this dissertation is to design a noninvasive, localized, and transient BBB opening system using focused ultrasound (FUS) and determine ultrasound and microbubble conditions that can effectively and safely deliver large pharmacologically-relevant-sized agents to the brain. To meet this end, an in vivo mouse brain drug delivery system using a stereotactic-based targeting method was developed. FUS was applied noninvasively through the intact skin and skull, which allowed for long-term and high-throughput studies. With this system, more than 150 mice were exposed to one of 31 distinct acoustic and microbubble conditions. The feasibility of delivering a large MRI contrast agent was first demonstrated in vivo in both wild-type and transgenic Alzheimer's disease model (APP/PS1) mice. A wide range of acoustic and microbubble conditions were then evaluated for their ability to deliver agents to a target region. Interestingly, the possible design space of parameters was found to be vast and different conditions resulted in distinct spatial distributions and doses delivered. In particular, BBB opening was shown to be dependent on the microbubble diameter, acoustic pressure, pulse repetition frequency (PRF), and pulse length (PL). Each set of

  10. Gauge unification, non-local breaking, open strings

    International Nuclear Information System (INIS)

    Trapletti, M.

    2005-01-01

    The issue of non-local GUT symmetry breaking is addressed in the context of open string model building. We study Z N xZ M ' orbifolds with all the GUT-breaking orbifold elements acting freely, as rotations accompanied by translations in the internal space. We consider open strings quantized on these backgrounds, distinguishing whether the translational action is parallel or perpendicular to the D-branes. GUT breaking is impossible in the purely perpendicular case, non-local GUT breaking is instead allowed in the purely parallel case. In the latter, the scale of breaking is set by the compactification moduli, and there are no fixed points with reduced gauge symmetry, where dangerous explicit GUT-breaking terms could be located. We investigate the mixed parallel+perpendicular case in a Z 2 xZ 2 ' example, having also a simplified field theory realization. It is a new S 1 /Z 2 xZ 2 ' orbifold-GUT model, with bulk gauge symmetry SU(5)xSU(5) broken locally to the Standard Model gauge group. In spite of the locality of the GUT symmetry breaking, there is no localized contribution to the running of the coupling constants, and the unification scale is completely set by the length of S 1

  11. Open hemorrhoidectomy under local anesthesia for symptomatic ...

    African Journals Online (AJOL)

    standard treatment for prolapsed hemorrhoids. The procedure is commonly done under general or regional anesthesia. This study is aimed to assess the feasibility and tolerability of open – hemorrhoidectomy under local anaesthesia in our setting.

  12. Topology vs. Anderson localization: non-perturbative solutions in one dimension

    OpenAIRE

    Altland, Alexander; Bagrets, Dmitry; Kamenev, Alex

    2014-01-01

    We present an analytic theory of quantum criticality in quasi one-dimensional topological Anderson insulators. We describe these systems in terms of two parameters $(g,\\chi)$ representing localization and topological properties, respectively. Certain critical values of $\\chi$ (half-integer for $\\Bbb{Z}$ classes, or zero for $\\Bbb{Z}_2$ classes) define phase boundaries between distinct topological sectors. Upon increasing system size, the two parameters exhibit flow similar to the celebrated t...

  13. Investigation of the Safety of Focused Ultrasound-Induced Blood-Brain Barrier Opening in a Natural Canine Model of Aging.

    Science.gov (United States)

    O'Reilly, Meaghan Anne; Jones, Ryan Matthew; Barrett, Edward; Schwab, Anthony; Head, Elizabeth; Hynynen, Kullervo

    2017-01-01

    Rationale: Ultrasound-mediated opening of the Blood-Brain Barrier(BBB) has shown exciting potential for the treatment of Alzheimer's disease(AD). Studies in transgenic mouse models have shown that this approach can reduce plaque pathology and improve spatial memory. Before clinical translation can occur the safety of the method needs to be tested in a larger brain that allows lower frequencies be used to treat larger tissue volumes, simulating clinical situations. Here we investigate the safety of opening the BBB in half of the brain in a large aged animal model with naturally occurring amyloid deposits. Methods: Aged dogs naturally accumulate plaques and show associated cognitive declines. Low-frequency ultrasound was used to open the BBB unilaterally in aged beagles (9-11yrs, n=10) in accordance with institutionally approved protocols. Animals received either a single treatment or four weekly treatments. Magnetic resonance imaging(MRI) was used to guide the treatments and assess the tissue effects. The animals underwent neurological testing during treatment follow-up, and a follow-up MRI exam 1 week following the final treatment. Results: The permeability of the BBB was successfully increased in all animals (mean enhancement: 19±11% relative to untreated hemisphere). There was a single adverse event in the chronic treatment group that resolved within 24 hrs. Follow-up MRI showed the BBB to be intact with no evidence of tissue damage in all animals. Histological analysis showed comparable levels of microhemorrhage between the treated and control hemispheres in the prefrontal cortex (single/repeat treatment: 1.0±1.4 vs 0.4±0.5/5.2±1.8 vs. 4.0±2.0). No significant differences were observed in beta-amyloid load (single/repeat: p=0.31/p=0.98) although 3/5 animals in each group showed lower Aβ loads in the treated hemisphere. Conclusion: Whole-hemisphere opening of the BBB was well tolerated in the aged large animal brain. The treatment volumes and frequencies

  14. Olfactory source localization in the open field using one or both nostrils.

    Science.gov (United States)

    Welge-Lussen, A; Looser, G L; Westermann, B; Hummel, T

    2014-03-01

    This study aims to examine humans ́ abilities to localize odorants within the open field. Young participants were tested on a localization task using a relatively selective olfactory stimulus (2-phenylethyl-alcohol, PEA) and cineol, an odorant with a strong trigeminal component. Participants were blindfolded and had to localize an odorant source at 2 m distance (far-field condition) and a 0.4 m distance (near-field condition) with either two nostrils open or only one open nostril. For the odorant with trigeminal properties, the number of correct trials did not differ when one or both nostrils were used, while more PEA localization trials were correctly completed with both rather than one nostril. In the near-field condition, correct localization was possible in 72-80% of the trials, irrespective of the odorant and the number of nostrils used. Localization accuracy, measured as spatial deviation from the olfactory source, was significantly higher in the near-field compared to the far-field condition, but independent of the odorant being localized. Odorant localization within the open field is difficult, but possible. In contrast to the general view, humans seem to be able to exploit the two-nostril advantage with increasing task difficulty.

  15. Usage Trends of Open Access and Local Journals: A Korean Case Study.

    Science.gov (United States)

    Seo, Jeong-Wook; Chung, Hosik; Yun, Jungmin; Park, Jin Young; Park, Eunsun; Ahn, Yuri

    2016-01-01

    Articles from open access and local journals are important resources for research in Korea and the usage trends of these articles are important indicators for the assessment of the current research practice. We analyzed an institutional collection of published papers from 1998 to 2014 authored by researchers from Seoul National University, and their references from papers published between 1998 and 2011. The published papers were collected from Web of Science or Scopus and were analyzed according to the proportion of articles from open access journals. Their cited references from published papers in Web of Science were analyzed according to the proportion of local (South Korean) or open access journals. The proportion of open access papers was relatively stable until 2006 (2.5 ~ 5.2% in Web of Science and 2.7 ~ 4.2% in Scopus), but then increased to 15.9% (Web of Science) or 18.5% (Scopus) in 2014. We analyzed 2,750,485 cited references from 52,295 published papers. We found that the overall proportion of cited articles from local journals was 1.8% and that for open access journals was 3.0%. Citations of open access articles have increased since 2006 to 4.1% in 2011, although the increase in open access article citations was less than for open access publications. The proportion of citations from local journals was even lower. We think that the publishing / citing mismatch is a term to describe this difference, which is an issue at Seoul National University, where the number of published papers at open access or local journals is increasing but the number of citations is not. The cause of this discrepancy is multi-factorial but the governmental / institutional policies, social / cultural issues and authors' citing behaviors will explain the mismatch. However, additional measures are also necessary, such as the development of an institutional citation database and improved search capabilities with respect to local and open access documents.

  16. Usage Trends of Open Access and Local Journals: A Korean Case Study

    Science.gov (United States)

    Chung, Hosik; Yun, Jungmin; Park, Jin Young; Park, Eunsun; Ahn, Yuri

    2016-01-01

    Articles from open access and local journals are important resources for research in Korea and the usage trends of these articles are important indicators for the assessment of the current research practice. We analyzed an institutional collection of published papers from 1998 to 2014 authored by researchers from Seoul National University, and their references from papers published between 1998 and 2011. The published papers were collected from Web of Science or Scopus and were analyzed according to the proportion of articles from open access journals. Their cited references from published papers in Web of Science were analyzed according to the proportion of local (South Korean) or open access journals. The proportion of open access papers was relatively stable until 2006 (2.5 ~ 5.2% in Web of Science and 2.7 ~ 4.2% in Scopus), but then increased to 15.9% (Web of Science) or 18.5% (Scopus) in 2014. We analyzed 2,750,485 cited references from 52,295 published papers. We found that the overall proportion of cited articles from local journals was 1.8% and that for open access journals was 3.0%. Citations of open access articles have increased since 2006 to 4.1% in 2011, although the increase in open access article citations was less than for open access publications. The proportion of citations from local journals was even lower. We think that the publishing / citing mismatch is a term to describe this difference, which is an issue at Seoul National University, where the number of published papers at open access or local journals is increasing but the number of citations is not. The cause of this discrepancy is multi-factorial but the governmental / institutional policies, social / cultural issues and authors' citing behaviors will explain the mismatch. However, additional measures are also necessary, such as the development of an institutional citation database and improved search capabilities with respect to local and open access documents. PMID:27195948

  17. Usage Trends of Open Access and Local Journals: A Korean Case Study.

    Directory of Open Access Journals (Sweden)

    Jeong-Wook Seo

    Full Text Available Articles from open access and local journals are important resources for research in Korea and the usage trends of these articles are important indicators for the assessment of the current research practice. We analyzed an institutional collection of published papers from 1998 to 2014 authored by researchers from Seoul National University, and their references from papers published between 1998 and 2011. The published papers were collected from Web of Science or Scopus and were analyzed according to the proportion of articles from open access journals. Their cited references from published papers in Web of Science were analyzed according to the proportion of local (South Korean or open access journals. The proportion of open access papers was relatively stable until 2006 (2.5 ~ 5.2% in Web of Science and 2.7 ~ 4.2% in Scopus, but then increased to 15.9% (Web of Science or 18.5% (Scopus in 2014. We analyzed 2,750,485 cited references from 52,295 published papers. We found that the overall proportion of cited articles from local journals was 1.8% and that for open access journals was 3.0%. Citations of open access articles have increased since 2006 to 4.1% in 2011, although the increase in open access article citations was less than for open access publications. The proportion of citations from local journals was even lower. We think that the publishing / citing mismatch is a term to describe this difference, which is an issue at Seoul National University, where the number of published papers at open access or local journals is increasing but the number of citations is not. The cause of this discrepancy is multi-factorial but the governmental / institutional policies, social / cultural issues and authors' citing behaviors will explain the mismatch. However, additional measures are also necessary, such as the development of an institutional citation database and improved search capabilities with respect to local and open access documents.

  18. Focused ultrasound-mediated noninvasive blood-brain barrier modulation: preclinical examination of efficacy and safety in various sonication parameters.

    Science.gov (United States)

    Shin, Jaewoo; Kong, Chanho; Cho, Jae Sung; Lee, Jihyeon; Koh, Chin Su; Yoon, Min-Sik; Na, Young Cheol; Chang, Won Seok; Chang, Jin Woo

    2018-02-01

    OBJECTIVE The application of pharmacological therapeutics in neurological disorders is limited by the ability of these agents to penetrate the blood-brain barrier (BBB). Focused ultrasound (FUS) has recently gained attention for its potential application as a method for locally opening the BBB and thereby facilitating drug delivery into the brain parenchyma. However, this method still requires optimization to maximize its safety and efficacy for clinical use. In the present study, the authors examined several sonication parameters of FUS influencing BBB opening in small animals. METHODS Changes in BBB permeability were observed during transcranial sonication using low-intensity FUS in 20 adult male Sprague-Dawley rats. The authors examined the effects of FUS sonication with different sonication parameters, varying acoustic pressure, center frequency, burst duration, microbubble (MB) type, MB dose, pulse repetition frequency (PRF), and total exposure time. The focal region of BBB opening was identified by Evans blue dye. Additionally, H & E staining was used to identify blood vessel damage. RESULTS Acoustic pressure amplitude and burst duration were closely associated with enhancement of BBB opening efficiency, but these parameters were also highly correlated with tissue damage in the sonicated region. In contrast, MB types, MB dose, total exposure time, and PRF had an influence on BBB opening without conspicuous tissue damage after FUS sonication. CONCLUSIONS The study aimed to identify these influential conditions and provide safety and efficacy values for further studies. Future work based on the current results is anticipated to facilitate the implementation of FUS sonication for drug delivery in various CNS disease states in the near future.

  19. Co-creating an open platform at the local governance level: How openness is enacted in Zambia

    DEFF Research Database (Denmark)

    Baka, Vasiliki

    2016-01-01

    The open mode of thinking, acting and being has been associated with liberating, participatory and collaborative arrangements that have prompted us to redefine how research, science, innovation and citizenship are to be conceived. In an era where much is said about the ‘open society’ and open inn...... at the local governance level, with implications for both theory and practice....

  20. Contrasted study on the opening degree of blood-brain barriier after radiation therapy with SPECT and MRI

    International Nuclear Information System (INIS)

    Zhang Qing; Sun Aihua; Hu Yun; Zhang Li; Ye Hengguang

    2004-01-01

    The blood-brain barrier(BBB) is the largest barrier responsible for preventing direct contact between chemotherapeutic drugs in blood and tumors in brain, the permeability of BBB incease at different degree after brain irradiation in clinical brain tumors radiotherapy. Methods: In our study, 26 patients with metastatic brain tumors(21 cases in pr/mary lung carcinoma, 5 cases in breast carcinoma) were accepted the full brain irradiation. The detructive effects of radiation on the BBB were determined by the 99mTc-DTPA SPECT and the concentration ratio of methotrexate(MTX) in cerebrospinal fluid(CSF) and blood, the brain MRI before and after radiotherapy were retrospective contrasted study with SPECT. Results: the degree of destructive effect on the BBB was directly proportional to radiation doses. After a dose of 20Gy radiation to brain, the permeability of BBB inceased markedly(P<0.01). But in cases the dexamethasone(DXM) was administrated to decease the brain edema during radiotherapy, the permeability inceased less than that in patients without DXM(P<0.05). Conclutions: After 20Gy irradiation, the BBB would gradually open. At this time, chemotherapy is the best choice to improving the therapeutic effect. Dexamethasone was found to cause the decease in BBB permeability but no significant remission of brain edema. So, if the combination of radiotherapy and chemotherapy in treatment of metastatic brain tumors will be plan, the dexamethasone may be not used in expecting to deceasing the side effect and that no affecting the therapeutic effect. (authors)

  1. Expression and localization of claudins-3 and -12 in transformed human brain endothelium

    Directory of Open Access Journals (Sweden)

    Schrade Anja

    2012-02-01

    Full Text Available Abstract Background The aim of this study was to characterize the hCMEC/D3 cell line, an in vitro model of the human Blood Brain Barrier (BBB for the expression of brain endothelial specific claudins-3 and -12. Findings hCMEC/D3 cells express claudins-3 and -12. Claudin-3 is distinctly localized to the TJ whereas claudin -12 is observed in the perinuclear region and completely absent from TJs. We show that the expression of both proteins is lost in cell passage numbers where the BBB properties are no longer fully conserved. Expression and localization of claudin-3 is not modulated by simvastatin shown to improve barrier function in vitro and also recommended for routine hCMEC/D3 culture. Conclusions These results support conservation of claudin-3 and -12 expression in the hCMEC/D3 cell line and make claudin-3 a potential marker for BBB characteristics in vitro.

  2. 75 FR 13454 - Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY

    Science.gov (United States)

    2010-03-22

    ...-AA08 Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY AGENCY: Coast... navigable waters of Huntington Bay, New York due to the annual Fran Schnarr Open Water Championships. The..., ``Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY'' (Docket number USCG...

  3. 75 FR 38710 - Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY

    Science.gov (United States)

    2010-07-06

    ...-AA08 Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY AGENCY: Coast... Regulation on the navigable waters of Huntington Bay, New York due to the annual Fran Schnarr Open Water... ``Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY'' in the Federal...

  4. Opening the Blood-Brain Barrier with MR Imaging-guided Focused Ultrasound: Preclinical Testing on a Trans-Human Skull Porcine Model.

    Science.gov (United States)

    Huang, Yuexi; Alkins, Ryan; Schwartz, Michael L; Hynynen, Kullervo

    2017-01-01

    Purpose To develop and test a protocol in preparation for a clinical trial on opening the blood-brain barrier (BBB) with magnetic resonance (MR) imaging-guided focused ultrasound for the delivery of chemotherapy drugs to brain tumors. Materials and Methods The procedures were approved by the institutional animal care committee. A trans-human skull porcine model was designed for the preclinical testing. Wide craniotomies were applied in 11 pigs (weight, approximately 15 kg). A partial human skull was positioned over the animal's brain. A modified clinical MR imaging-guided focused ultrasound brain system was used with a 3.0-T MR unit. The ultrasound beam was steered during sonications over a 3 × 3 grid at 3-mm spacing. Acoustic power levels of 3-20 W were tested. Bolus injections of microbubbles at 4 μL/kg were tested for each sonication. Levels of BBB opening, hemorrhage, and cavitation signal were measured with MR imaging, histologic examination, and cavitation receivers, respectively. A cavitation safety algorithm was developed on the basis of logistic regression of the measurements and tested to minimize the risk of hemorrhage. Results BBB openings of approximately 1 cm 3 in volume were visualized with gadolinium-enhanced MR imaging after sonication at an acoustic power of approximately 5 W. Gross examination of histologic specimens helped confirm Evans blue (bound to macromolecule albumin) extravasation, and hematoxylin-eosin staining helped detect only scattered extravasation of red blood cells. In cases where cavitation signals were higher than thresholds, sonications were terminated immediately without causing hemorrhage. Conclusion With a trans-human skull porcine model, this study demonstrated BBB opening with a 230-kHz system in preparation for a clinical trial. © RSNA, 2016 Online supplemental material is available for this article.

  5. Submicron-bubble-enhanced focused ultrasound for blood-brain barrier disruption and improved CNS drug delivery.

    Directory of Open Access Journals (Sweden)

    Ching-Hsiang Fan

    Full Text Available The use of focused ultrasound (FUS with microbubbles has been proven to induce transient blood-brain barrier opening (BBB-opening. However, FUS-induced inertial cavitation of microbubbles can also result in erythrocyte extravasations. Here we investigated whether induction of submicron bubbles to oscillate at their resonant frequency would reduce inertial cavitation during BBB-opening and thereby eliminate erythrocyte extravasations in a rat brain model. FUS was delivered with acoustic pressures of 0.1-4.5 MPa using either in-house manufactured submicron bubbles or standard SonoVue microbubbles. Wideband and subharmonic emissions from bubbles were used to quantify inertial and stable cavitation, respectively. Erythrocyte extravasations were evaluated by in vivo post-treatment magnetic resonance susceptibility-weighted imaging, and finally by histological confirmation. We found that excitation of submicron bubbles with resonant frequency-matched FUS (10 MHz can greatly limit inertial cavitation while enhancing stable cavitation. The BBB-opening was mainly caused by stable cavitation, whereas the erythrocyte extravasation was closely correlated with inertial cavitation. Our technique allows extensive reduction of inertial cavitation to induce safe BBB-opening. Furthermore, the safety issue of BBB-opening was not compromised by prolonging FUS exposure time, and the local drug concentrations in the brain tissues were significantly improved to 60 times (BCNU; 18.6 µg versus 0.3 µg by using chemotherapeutic agent-loaded submicron bubbles with FUS. This study provides important information towards the goal of successfully translating FUS brain drug delivery into clinical use.

  6. Local Open Innovation: How to Go from Ideas to Solutions

    Directory of Open Access Journals (Sweden)

    Oscar Smulders

    2013-03-01

    Full Text Available Local open innovation can be used to create a powerful dynamic within a local multi-stakeholder environment. This article shares the experiences of setting up a collaborative innovation process in a regional initiative in the Netherlands. In the first phase of the process, a couple of interactive idea generating sessions have been organized. These so called Quest for Solutions sessions have not only generated a rich set of useful solutions, but they also created a positive vibe within the local community. Factors that have contributed to the success of the idea generation sessions are working around real-life problems involving people who are directly affected by the problem. The structure of the sessions with alternating phases of divergence, exploration, and convergence allowed for broad understanding of the problems, exploration of potential solutions, and working towards result-oriented value statements. Key challenges in translating the ideas into solutions have been determining the value case and dealing with intellectual property. Special attention is given to the notion of innovative contract design as a means of dealing with intellectual property in an environment of local open innovation.

  7. Pharmacological treatment and BBB-targeted genetic therapy for MCT8-dependent hypomyelination in zebrafish

    Directory of Open Access Journals (Sweden)

    David Zada

    2016-11-01

    Full Text Available Hypomyelination is a key symptom of Allan-Herndon-Dudley syndrome (AHDS, a psychomotor retardation associated with mutations in the thyroid-hormone (TH transporter MCT8 (monocarboxylate transporter 8. AHDS is characterized by severe intellectual deficiency, neuromuscular impairment and brain hypothyroidism. In order to understand the mechanism for TH-dependent hypomyelination, we developed an mct8 mutant (mct8−/− zebrafish model. The quantification of genetic markers for oligodendrocyte progenitor cells (OPCs and mature oligodendrocytes revealed reduced differentiation of OPCs into oligodendrocytes in mct8−/− larvae and adults. Live imaging of single glial cells showed that the number of oligodendrocytes and the length of their extensions are reduced, and the number of peripheral Schwann cells is increased, in mct8−/− larvae compared with wild type. Pharmacological analysis showed that TH analogs and clemastine partially rescued the hypomyelination in the CNS of mct8−/− larvae. Intriguingly, triiodothyronine (T3 treatment rescued hypomyelination in mct8−/− embryos before the maturation of the blood–brain barrier (BBB, but did not affect hypomyelination in older larvae. Thus, we expressed Mct8-tagRFP in the endothelial cells of the vascular system and showed that even relatively weak mosaic expression completely rescued hypomyelination in mct8−/− larvae. These results suggest potential pharmacological treatments and BBB-targeted gene therapy that can enhance myelination in AHDS and possibly in other TH-dependent brain disorders.

  8. Bicuculline methiodide in the blood-brain barrier-epileptogen model of epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Remler, M.P.; Marcussen, W.H.

    Focal epilepsy can be produced by a blood-brain barrier (BBB)-excluded systemic convulsant (penicillin, folic acid, etc.) in the presence of a focal BBB lesion. Bicuculline methiodide, a gamma-aminobutyric acid blocking epileptogen, crosses the normal BBB of rats poorly and produces no consistent abnormality behaviorally or on EEG at 36 mg/kg. When the BBB is opened in 0.25 ml of cortex by 6,000 rad of alpha particles, by a pin trauma lesion, or by a heat lesion, the rats are normal clinically and on EEG. When these lesioned rats are challenged with bicuculline methiodide, 36 mg/kg, an intense, highly localized epileptiform discharge results that begins approximately 20 min after injection and lasts 30-90 min. The plausibility and experimental utility of the BBB-epileptogen model of epilepsy are enhanced by these observations.

  9. Tip opening of premixed bunsen flames: Extinction with negative stretch and local Karlovitz number

    KAUST Repository

    Vu, Tranmanh

    2015-04-01

    The characteristics of tip openings in premixed bunsen flames have been studied experimentally by measuring OH radicals from laser-induced fluorescence and tip curvatures from chemiluminescent images. Results showed that the tip opening occurred at a constant equivalence ratio and was independent of the jet velocity in propane/air mixtures. The observation of a local extinction phenomenon of the negatively stretched flame due to the flame curvature could not be consistently explained based on flame stretch or the Karlovitz number, since they varied appreciably with the jet velocity. The concept of the local Karlovitz number (KaL) was introduced, which is defined as the ratio of the characteristic reaction time in the normal direction for a stretched flame to the characteristic flow time in the tangential direction for the stretched flame. The local Karlovitz number maintained a constant value under tip opening conditions, irrespective of the jet velocity. Tip opening occurred at a reasonably constant local Karlovitz number of about ~1.72 when the nitrogen dilution level in propane and n-butane fuels was varied.

  10. Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Agrawal, Mukta; Ajazuddin; Tripathi, Dulal K; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G; Mourtas, Spyridon; Hammarlund-Udenaes, Margareta; Alexander, Amit

    2017-08-28

    In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiological barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug molecules, various proteins and peptides, small hydrophilic molecules, large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli. This functionally essential structure creates a major hurdle for delivery of any drug into the brain. Still, there are some provisions on BBB which facilitate the entry of useful substances in the brain via specific mechanisms like passive diffusion, receptor-mediated transcytosis, carrier-mediated transcytosis etc. Another important factor for drug transport is the selection of a suitable drug delivery systems like, liposome, which is a novel drug carrier system offering a potential approach to resolving this problem. Its unique phospholipid bilayer structure (similar to physiological membrane) had made it more compatible with the lipoidal layer of BBB and helps the drug to enter the brain. The present review work focused on various surface modifications with functional ligand (like lactoferrin, transferrin etc.) and carrier molecules (such as glutathione, glucose etc.) on the liposomal structure to enhance its brain targeting ability towards the successful treatment of Alzheimer disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Kaempferol alleviates LPS-induced neuroinflammation and BBB dysfunction in mice via inhibiting HMGB1 release and down-regulating TLR4/MyD88 pathway.

    Science.gov (United States)

    Cheng, Xiao; Yang, Ying-Lin; Yang, Huan; Wang, Yue-Hua; Du, Guan-Hua

    2018-03-01

    Kaempferol is a natural flavonoid with many biological activities including anti-oxidation and anti-inflammation. Nevertheless, its anti-neuroinflammation role and the relevant mechanism remain unclear. The present study was to investigate effects of kaempferol against LPS-induced neuroinflammation and blood-brain barrier dysfunction as well as the mechanism in mice. BALB/c mice were treated with LPS 5mg/kg to induce inflammation after pre-treatment with kaempferol 25, 50, or 100mg/kg for 7days. The results showed that kaempferol reduced the production of various pro-inflammatory factors and inflammatory proteins including IL-1β, IL-6, TNF-α, MCP-1, COX-2 and iNOS in brain tissues. In addition, kaempferol also protected BBB integrity and increased BBB related proteins including occludin-1, claudin-1 and CX43 in brain of LPS-induced mice. Furthermore, kaempferol significantly reduced HMGB1 level and suppressed TLR4/MyD88 inflammatory pathway in both transcription level and translation level. These results collectively suggested that kaempferol might be a promising neuroprotective agent for alleviating inflammatory responses and BBB dysfunction by inhibiting HMGB1 release and down-regulating TLR4/MyD88 inflammatory pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Localization of pellicle-induced open contacts using Charge-Induced Voltage Alteration

    Energy Technology Data Exchange (ETDEWEB)

    Cole, E.I. Jr.; Soden, J.M.

    1993-08-01

    The recently developed Charge-Induced Voltage Alteration (CIVA) technique for localizing open metal conductors was used successfully to identify transistors with electrically open metal-1 contacts to silicon. The transistors were in the I/O port circuitry of a failing microcontroller and were completely covered by a metal-2 power bus. The root cause of the open contacts was a subtle scratch in the pellicle over the contact reticle. The scratch prevented full exposure of the photoresist, resulting in incomplete removal of the interlevel oxide in several contact windows. In addition to this powerful new application of CIVA, a number of failure analysis techniques utilizing both the electrical and physical properties of the failing microcontrollers were employed to identify and confirm the open contacts. These techniques are reviewed and recommendations are given for improved pellicle/reticle inspection.

  13. Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task.

    Science.gov (United States)

    Downs, Matthew E; Buch, Amanda; Sierra, Carlos; Karakatsani, Maria Eleni; Teichert, Tobias; Chen, Shangshang; Konofagou, Elisa E; Ferrera, Vincent P

    2015-01-01

    Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500 kHz, 200-400 kPa, 4-5 μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4-20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of' visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4-5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used.

  14. Openness to Change: Experiential and Demographic Components of Change in Local Health Department Leaders

    OpenAIRE

    Jadhav, Emmanuel D.; Holsinger, James W.; Fardo, David W.

    2015-01-01

    Background During the 2008–2010 economic recession, Kentucky local health department (LHD) leaders utilized innovative strategies to maintain their programs. A characteristic of innovative strategy is leader openness to change. Leader demographical research in for-profit organizations has yielded valuable insight into leader openness to change. For LHD leaders, the nature of the association between leader demographic and organizational characteristics on leader openness to change is unknow...

  15. NOX4-dependent neuronal autotoxicity and BBB breakdown explain the superior sensitivity of the brain to ischemic damage.

    Science.gov (United States)

    Casas, Ana I; Geuss, Eva; Kleikers, Pamela W M; Mencl, Stine; Herrmann, Alexander M; Buendia, Izaskun; Egea, Javier; Meuth, Sven G; Lopez, Manuela G; Kleinschnitz, Christoph; Schmidt, Harald H H W

    2017-11-14

    Ischemic injury represents the most frequent cause of death and disability, and it remains unclear why, of all body organs, the brain is most sensitive to hypoxia. In many tissues, type 4 NADPH oxidase is induced upon ischemia or hypoxia, converting oxygen to reactive oxygen species. Here, we show in mouse models of ischemia in the heart, brain, and hindlimb that only in the brain does NADPH oxidase 4 (NOX4) lead to ischemic damage. We explain this distinct cellular distribution pattern through cell-specific knockouts. Endothelial NOX4 breaks down the BBB, while neuronal NOX4 leads to neuronal autotoxicity. Vascular smooth muscle NOX4, the common denominator of ischemia within all ischemic organs, played no apparent role. The direct neuroprotective potential of pharmacological NOX4 inhibition was confirmed in an ex vivo model, free of vascular and BBB components. Our results demonstrate that the heightened sensitivity of the brain to ischemic damage is due to an organ-specific role of NOX4 in blood-brain-barrier endothelial cells and neurons. This mechanism is conserved in at least two rodents and humans, making NOX4 a prime target for a first-in-class mechanism-based, cytoprotective therapy in the unmet high medical need indication of ischemic stroke. Copyright © 2017 the Author(s). Published by PNAS.

  16. Combined computational-experimental approach to predict blood-brain barrier (BBB) permeation based on "green" salting-out thin layer chromatography supported by simple molecular descriptors.

    Science.gov (United States)

    Ciura, Krzesimir; Belka, Mariusz; Kawczak, Piotr; Bączek, Tomasz; Markuszewski, Michał J; Nowakowska, Joanna

    2017-09-05

    The objective of this paper is to build QSRR/QSAR model for predicting the blood-brain barrier (BBB) permeability. The obtained models are based on salting-out thin layer chromatography (SOTLC) constants and calculated molecular descriptors. Among chromatographic methods SOTLC was chosen, since the mobile phases are free of organic solvent. As consequences, there are less toxic, and have lower environmental impact compared to classical reserved phases liquid chromatography (RPLC). During the study three stationary phase silica gel, cellulose plates and neutral aluminum oxide were examined. The model set of solutes presents a wide range of log BB values, containing compounds which cross the BBB readily and molecules poorly distributed to the brain including drugs acting on the nervous system as well as peripheral acting drugs. Additionally, the comparison of three regression models: multiple linear regression (MLR), partial least-squares (PLS) and orthogonal partial least squares (OPLS) were performed. The designed QSRR/QSAR models could be useful to predict BBB of systematically synthesized newly compounds in the drug development pipeline and are attractive alternatives of time-consuming and demanding directed methods for log BB measurement. The study also shown that among several regression techniques, significant differences can be obtained in models performance, measured by R 2 and Q 2 , hence it is strongly suggested to evaluate all available options as MLR, PLS and OPLS. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Effects of user training with electronically-modulated sound transmission hearing protectors and the open ear on horizontal localization ability.

    Science.gov (United States)

    Casali, John G; Robinette, Martin B

    2015-02-01

    To determine if training with electronically-modulated hearing protection (EMHP) and the open ear results in auditory learning on a horizontal localization task. Baseline localization testing was conducted in three listening conditions (open-ear, in-the-ear (ITE) EMHP, and over-the-ear (OTE) EMHP). Participants then wore either an ITE or OTE EMHP for 12, almost daily, one-hour training sessions. After training was complete, participants again underwent localization testing in all three listening conditions. A computer with a custom software and hardware interface presented localization sounds and collected participant responses. Twelve participants were recruited from the student population at Virginia Tech. Audiometric requirements were 35 dBHL at 500, 1000, and 2000 Hz bilaterally, and 55 dBHL at 4000 Hz in at least one ear. Pre-training localization performance with an ITE or OTE EMHP was worse than open-ear performance. After training with any given listening condition, including open-ear, performance in that listening condition improved, in part from a practice effect. However, post-training localization performance showed near equal performance between the open-ear and training EMHP. Auditory learning occurred for the training EMHP, but not for the non-training EMHP; that is, there was no significant training crossover effect between the ITE and the OTE devices. It is evident from this study that auditory learning (improved horizontal localization performance) occurred with the EMHP for which training was performed. However, performance improvements found with the training EMHP were not realized in the non-training EMHP. Furthermore, localization performance in the open-ear condition also benefitted from training on the task.

  18. Organic cation transporter 1 (OCT1 is involved in pentamidine transport at the human and mouse blood-brain barrier (BBB.

    Directory of Open Access Journals (Sweden)

    Gayathri N Sekhar

    Full Text Available Pentamidine is an effective trypanocidal drug used against stage 1 Human African Trypanosomiasis (HAT. At the blood-brain barrier (BBB, it accumulates inside the endothelial cells but has limited entry into the brain. This study examined transporters involved in pentamidine transport at the human and mouse BBB using hCMEC/D3 and bEnd.3 cell lines, respectively. Results revealed that both cell lines expressed the organic cation transporters (OCT1, OCT2 and OCT3, however, P-gp was only expressed in hCMEC/D3 cells. Polarised expression of OCT1 was also observed. Functional assays found that ATP depletion significantly increased [3H]pentamidine accumulation in hCMEC/D3 cells (***p<0.001 but not in bEnd.3 cells. Incubation with unlabelled pentamidine significantly decreased accumulation in hCMEC/D3 and bEnd.3 cells after 120 minutes (***p<0.001. Treating both cell lines with haloperidol and amantadine also decreased [3H]pentamidine accumulation significantly (***p<0.001 and **p<0.01 respectively. However, prazosin treatment decreased [3H]pentamidine accumulation only in hCMEC/D3 cells (*p<0.05, and not bEnd.3 cells. Furthermore, the presence of OCTN, MATE, PMAT, ENT or CNT inhibitors/substrates had no significant effect on the accumulation of [3H]pentamidine in both cell lines. From the data, we conclude that pentamidine interacts with multiple transporters, is taken into brain endothelial cells by OCT1 transporter and is extruded into the blood by ATP-dependent mechanisms. These interactions along with the predominant presence of OCT1 in the luminal membrane of the BBB contribute to the limited entry of pentamidine into the brain. This information is of key importance to the development of pentamidine based combination therapies which could be used to treat CNS stage HAT by improving CNS delivery, efficacy against trypanosomes and safety profile of pentamidine.

  19. Optimization of the Ultrasound-Induced Blood-Brain Barrier Opening

    OpenAIRE

    Konofagou, Elisa E.

    2012-01-01

    Current treatments of neurological and neurodegenerative diseases are limited due to the lack of a truly non-invasive, transient, and regionally selective brain drug delivery method. The brain is particularly difficult to deliver drugs to because of the blood-brain barrier (BBB). The impermeability of the BBB is due to the tight junctions connecting adjacent endothelial cells and highly regulatory transport systems of the endothelial cell membranes. The main function of the BBB is ion and vol...

  20. Localization and traces in open-closed topological Landau-Ginzburg models

    International Nuclear Information System (INIS)

    Herbst, Manfred; Lazaroiu, Calin-Iuliu

    2005-01-01

    We reconsider the issue of localization in open-closed B-twisted Landau-Ginzburg models with arbitrary Calabi-Yau target. Through careful analysis of zero-mode reduction, we show that the closed model allows for a one-parameter family of localization pictures, which generalize the standard residue representation. The parameter λ which indexes these pictures measures the area of worldsheets with S 2 topology, with the residue representation obtained in the limit of small area. In the boundary sector, we find a double family of such pictures, depending on parameters λ and μ which measure the area and boundary length of worldsheets with disk topology. We show that setting μ = 0 and varying λ interpolates between the localization picture of the B-model with a noncompact target space and a certain residue representation proposed recently. This gives a complete derivation of the boundary residue formula, starting from the explicit construction of the boundary coupling. We also show that the various localization pictures are related by a semigroup of homotopy equivalences

  1. Localization of effective actions in open superstring field theory

    Science.gov (United States)

    Maccaferri, Carlo; Merlano, Alberto

    2018-03-01

    We consider the construction of the algebraic part of D-branes tree-level effective action from Berkovits open superstring field theory. Applying this construction to the quartic potential of massless fields carrying a specific worldsheet charge, we show that the full contribution to the potential localizes at the boundary of moduli space, reducing to elementary two-point functions. As examples of this general mechanism, we show how the Yang-Mills quartic potential and the instanton effective action of a Dp/D( p - 4) system are reproduced.

  2. Differential blood-brain barrier permeabilities to [14C]sucrose and [3H]inulin after osmotic opening in the rat

    International Nuclear Information System (INIS)

    Ziylan, Y.Z.; Robinson, P.J.; Rapoport, S.I.

    1983-01-01

    The blood-brain barrier (B-BB) in 3-month-old rats was opened unilaterally by infusing 1.8 m L(+)arabinose in water into the internal carotid artery through a catheter in the external carotid. Two poorly penetrating uncharged test radiotracers of differing molecular weight and size, [ 14 C]sucrose (340 daltons, radius 5 A) and [ 3 H]inulin (5500 daltons, radius 15 A), were simultaneously injected i.v. in untreated rats, or rats at 1, 30, or 50 min after infusion of hypertonic arabinose solution. Evans-blue solution was injected 5 min prior to osmotic treatment as a visual indicator of barrier integrity. In regions of uninfused control brains, the [ 14 C]sucrose permeability-surface area (PA) product approximated 10(-5) s-1, whereas PA was not measurable for [ 3 H]inulin. In arabinose-infused animals, PA products on the ipsilateral hemisphere for both [ 14 C]sucrose and [ 3 H]inulin were markedly elevated 6 min after infusion, but decreased by 35 and 55 min. In nearly all regions, statistically significant differences were not found between 6-min [ 14 C]sucrose- and [ 3 H]inulin-PA values (P greater than 0.05). However, at 35 and 55 min in most regions, the PA for [ 3 H]inulin was significantly lower (P less than 0.05) than PA for [ 14 C]sucrose. The results indicated that the B-BB closed more rapidly to larger than to smaller molecules after osmotic treatment and were consistent with a pore model for osmotic B-BB opening

  3. Improved open-sun drying method for local swamp rice in Uganda ...

    African Journals Online (AJOL)

    “Kaiso” and “Supa” are the main local swamp-rice (Oryza Sativa) varieties currently grown in Uganda mainly by smallholder farmers on small gardens (0.5 – 2ha). Due to lack of mechanized drying equipment and owing to the low volumes of their harvests, these farmers use open-sun drying methods, where the paddy is ...

  4. Openness to change: experiential and demographic components of change in in Local Health Department leaders

    OpenAIRE

    Emmanuel D Jadhav; James W. Holsinger; David W Fardo

    2015-01-01

    Background: During the 2008-10 economic recession, Kentucky local health department (LHD) leaders utilized innovative strategies to maintain their programs. A characteristic of innovative strategy is leader openness to change. Leader demographical research in for-profit organizations has yielded valuable insight into leader openness to change. For LHD leaders the nature of the association between leader demographic and organizational characteristics on leader openness to change is unknown. Th...

  5. Preoperative localization and biopsy of non-palpable breast lesions with a special localization device on the Magnetom Open; Praeoperative Markierung und Biopsie nicht palpabler Mammalaesionen mit einer Zieleinrichtung am Magnetom Open

    Energy Technology Data Exchange (ETDEWEB)

    Sittek, H.; Linsmeier, E.; Perlet, C.; Schneider, P.; Baudrexel, C.; Reiser, M. [Klinikum Grosshadern, Muenchen (Germany). Inst. fuer Klinische Radiologie; Untch, M. [Klinikum Grosshadern, Muenchen (Germany). Klinik und Poliklinik fuer Frauenheilkunde und Geburtshilfe

    2000-11-01

    Purpose. MRI-guided interventional maneuvers in the breast, when closed MRi scanners are employed are relatively complex and time consuming. The purpose of our investigations was to develop a special device for the localization and biopsy of breast lesions using an open low-field MRI Scanner (Magnetom Open, Siemens, Erlangen, Germany) permitting free access to the patient. Materials and methods. Due to its particular material and construction characteristics, a newly developed device for localization and biopsy of breast lesions is appropriate to remain within the magnetic field during the examination without degrading image quality. We performed 125 tests in a phantom and 31 investigations in patients including 26 wire-localizations and 5 biopsies. Results. The interventional maneuvers in the phantom could be performed very precisely. In all 125 phantom studies, the needle (14G coaxial biopsy cannula, Bard) was positioned close to the simulated lesion. In 25 out of 26 patients the needle was positioned within a distance less than 5 mm from the lesion. When using the 14G coaxial biopsy cannula (Bard, Karlsruhe, Germany) the needle tip was found adjacent next to the lesion in all 12 cases (7 wire-localizations, 5 biopsies). Conclusions. Our results indicate that our device allows very precise preoperative localization of breast lesions within the Magnetom Open. Using MRI-compatible, large-core needles, biopsy under direct MRI control resulted in good results. (orig.) [German] Zielsetzung. Am geschlossenen MRT-Geraet sind Interventionen an der Mamma relativ aufwendig und zeitintensiv. Ziel unserer Untersuchungen war es, eine Lokalisations- und Biopsieeinrichtung fuer das offene MRT-Geraet (Magnetom Open, Siemens) zu entwickeln und zu erproben. Patienten und Methode. Es wurde eine Lokalisations- und Biopsieeinrichtung entwickelt, die aufgrund ihrer Bauart waehrend der Intervention im Magnetfeld des MRT-Geraetes verbleiben kann und die Bildgebung nicht nachteilig

  6. The role of local stress perturbation on the simultaneous opening of orthogonal fractures

    Science.gov (United States)

    Boersma, Quinten; Hardebol, Nico; Barnhoorn, Auke; Bertotti, Giovanni; Drury, Martyn

    2016-04-01

    Orthogonal fracture networks (ladder-like networks) are arrangements that are commonly observed in outcrop studies. They form a particularly dense and well connected network which can play an important role in the effective permeability of tight hydrocarbon or geothermal reservoirs. One issue is the extent to which both the long systematic and smaller cross fractures can be simultaneously critically stressed under a given stress condition. Fractures in an orthogonal network form by opening mode-I displacements in which the main component is separation of the two fracture walls. This opening is driven by effective tensile stresses as the smallest principle stress acting perpendicular to the fracture wall, which accords with linear elastic fracture mechanics. What has been well recognized in previous field and modelling studies is how both the systematic fractures and perpendicular cross fractures require the minimum principle stress to act perpendicular to the fracture wall. Thus, these networks either require a rotation of the regional stress field or local perturbations in stress field. Using a mechanical finite element modelling software, a geological case of layer perpendicular systematic mode I opening fractures is generated. New in our study is that we not only address tensile stresses at the boundary, but also address models using pore fluid pressure. The local stress in between systematic fractures is then assessed in order to derive the probability and orientation of micro crack propagation using the theory of sub critical crack growth and Griffith's theory. Under effective tensile conditions, the results indicate that in between critically spaced systematic fractures, local effective tensile stresses flip. Therefore the orientation of the least principle stress will rotate 90°, hence an orthogonal fracture is more likely to form. Our new findings for models with pore fluid pressures instead of boundary tension show that the magnitude of effective tension

  7. Opening complete band gaps in two dimensional locally resonant phononic crystals

    Science.gov (United States)

    Zhou, Xiaoling; Wang, Longqi

    2018-05-01

    Locally resonant phononic crystals (LRPCs) which have low frequency band gaps attract a growing attention in both scientific and engineering field recently. Wide complete locally resonant band gaps are the goal for researchers. In this paper, complete band gaps are achieved by carefully designing the geometrical properties of the inclusions in two dimensional LRPCs. The band structures and mechanisms of different types of models are investigated by the finite element method. The translational vibration patterns in both the in-plane and out-of-plane directions contribute to the full band gaps. The frequency response of the finite periodic structures demonstrate the attenuation effects in the complete band gaps. Moreover, it is found that the complete band gaps can be further widened and lowered by increasing the height of the inclusions. The tunable properties by changing the geometrical parameters provide a good way to open wide locally resonant band gaps.

  8. Study of the efficiency of transplantation of human neural stem cells to rats with spinal trauma: the use of functional load tests and BBB test.

    Science.gov (United States)

    Lebedev, S V; Karasev, A V; Chekhonin, V P; Savchenko, E A; Viktorov, I V; Chelyshev, Yu A; Shaimardanova, G F

    2010-09-01

    Human ensheating neural stem cells of the olfactory epithelium were transplanted to adult male rats immediately after contusion trauma of the spinal cord at T9 level rostrally and caudally to the injury. Voluntary movements (by a 21-point BBB scale), rota-rod performance, and walking along a narrowing beam were monitored weekly over 60 days. In rats receiving cell transplantation, the mean BBB score significantly increased by 11% by the end of the experiment. The mean parameters of load tests also regularly surpassed the corresponding parameters in controls. The efficiency of transplantation (percent of animals with motor function recovery parameters surpassing the corresponding mean values in the control groups) was 62% by the state of voluntary motions, 37% by the rota-rod test, and 32% by the narrowing beam test. Morphometry revealed considerable shrinking of the zone of traumatic damage in the spinal cord and activation of posttraumatic remyelination in animals receiving transplantation of human neural stem cells.

  9. Identifying Socio-Cultural Factors That Impact the Use of Open Educational Resources in Local Public Administrations

    OpenAIRE

    Julia Stoffregen; Jan M. Pawlowski; Eric Ras; Snezana Scepanovic; Dragica Zugic

    2016-01-01

    The goal of this paper is to define relevant barriers to the exchange of Open Educational Resources in local public administrations. Building upon a cultural model, eleven experts were interviewed and asked to evaluate several factors, such as openness in discourse, learning at the workplace, and superior support, among others. The result is a set of socio-cultural factors that shape the use of Open Educational Resources in public administrations. Significant factors are, in...

  10. Evaluation of blood--brain barrier permeability changes in rhesus monkeys and man using 82Rb and positron emission tomography

    International Nuclear Information System (INIS)

    Yen, C.K.; Budinger, T.F.

    1981-01-01

    Dynamic positron tomography of the brain with 82 Rb, obtained from a portable generator [ 82 Sr (25 days) -- 82 Rb (76 sec)], provides a means of studying blood-brain barrier (BBB) permeability in physiological and clinical investigations. The BBB in rhesus monkeys was opened unilaterally by intracarotid infusion of 3 M urea. This osmotic barrier opening allowed entry into the brain of intravenously administered rubidium chloride. The BBB opening was demonstrated noninvasively using 82 Rb and positron emission tomography and corroborated by the accumulation of 86 Rb in tissue samples. Positron emission tomography studies can be repeated every 5 min and indicate that dynamic tomography or static imaging can be used to study BBB permeability changes induced by a wide variety of noxious stimuli. Brain tumors in human subjects are readily detected because of the usual BBB permeability disruption in and around the tumors

  11. 78 FR 33700 - Special Local Regulations for Marine Events, Pleasantville Aquatics 15th Annual 5K Open Water...

    Science.gov (United States)

    2013-06-05

    ...-AA08 Special Local Regulations for Marine Events, Pleasantville Aquatics 15th Annual 5K Open Water Swim... Waterway for the Pleasantville Aquatics 15th Annual 5K Open Water Swim. The Captain of the Port, Sector..., Pleasantville Aquatics 15th Annual 5K Open Water Swim, Intracoastal Waterway; Atlantic City, NJ. (a) Location...

  12. Chronic Open Infective Lateral Malleolus Bursitis Management Using Local Rotational Flap

    Directory of Open Access Journals (Sweden)

    Yong-Beom Lee

    2017-01-01

    Full Text Available Background. Using a sinus tarsi rotational flap is an uncommon approach to treating chronic open infective lateral malleolus bursitis. Methods. We treated eight patients, including six males, using this approach. First, we debrided all the infected tissues and used a negative pressure wound closure system where needed. After acute infection had been controlled, the local rotational flap was used for cases where the wound could not be closed by a simple suture or bone exposure. The rotational flap was detached with a curved skin incision at the sinus tarsi next to the open wound and sutured to the defect, paying careful attention to the superficial peroneal nerve. The donor site was managed with a split-thickness skin graft. Results. The patients’ mean age was 74.1 years. Six patients had a wound after suppurative infection, but two patients had ulcer-type bursitis. Six patients demonstrated full flap healing, but two patients had venous congestion necrosis. Conclusion. A sinus tarsi rotational flap is a useful method to ensure healing and coverage of chronic open lateral malleolus bursitis, especially for small to medium wounds with cavity and bone exposure.

  13. The collaboration between and contribution of a digital open innovation platform to a local design process

    DEFF Research Database (Denmark)

    del Castillo, Jacqueline; Bhatti, Yasser; Hossain, Mokter

    2017-01-01

    We examine the potential of an open innovation digital platform to expose a local innovation process to a greater number of ideas and a more inclusive set of stakeholders. To do so we studied an online innovation challenge on the OpenIDEO to reimagine the end-of-life experience sponsored by Sutte...... it leads to a greater number of ideas from a wider and more inclusive set of stakeholders. We offer insights for the literatures on open innovation and design thinking in a healthcare context....

  14. Facilitation of Drug Transport across the Blood–Brain Barrier with Ultrasound and Microbubbles

    OpenAIRE

    Meairs, Stephen

    2015-01-01

    Medical treatment options for central nervous system (CNS) diseases are limited due to the inability of most therapeutic agents to penetrate the blood–brain barrier (BBB). Although a variety of approaches have been investigated to open the BBB for facilitation of drug delivery, none has achieved clinical applicability. Mounting evidence suggests that ultrasound in combination with microbubbles might be useful for delivery of drugs to the brain through transient opening of the BBB. This techni...

  15. A comparison of laparoscopic and open surgery following pre-operative chemoradiation therapy for locally advanced lower rectal cancer

    International Nuclear Information System (INIS)

    Kusano, Toru; Inomata, Masafumi; Hiratsuka, Takahiro

    2014-01-01

    Although pre-operative chemoradiation therapy for advanced lower rectal cancer is a controversial treatment modality, it is increasingly used in combination with surgery. Few studies have considered the combination of chemoradiation therapy followed by laparoscopic surgery for locally advanced lower rectal cancer; therefore, this study aimed to assess the usefulness of this therapeutic combination. We retrospectively reviewed the medical records of patients with locally advanced lower rectal cancer treated by pre-operative chemoradiation therapy and surgery from February 2002 to November 2012 at Oita University. We divided patients into an open surgery group and a laparoscopic surgery group and evaluated various parameters by univariate and multivariate analyses. In total, 33 patients were enrolled (open surgery group, n=14; laparoscopic surgery group, n=19). Univariate analysis revealed that compared with the open surgery group, operative time was significantly longer, whereas intra-operative blood loss and intra-operative blood transfusion requirements were significantly less in the laparoscopic surgery group. There were no significant differences in post-operative complication and recurrence rates between the two groups. According to multivariate analysis, operative time and intra-operative blood loss were significant predictors of outcome in the laparoscopic surgery group. This study suggests that laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is a safe procedure. Further prospective investigation of the long-term oncological outcomes of laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is required to confirm the advantages of laparoscopic surgery over open surgery. (author)

  16. 77 FR 23120 - Special Local Regulations; Lowcountry Splash Open Water Swim, Wando River and Cooper River, Mount...

    Science.gov (United States)

    2012-04-18

    ...-AA08 Special Local Regulations; Lowcountry Splash Open Water Swim, Wando River and Cooper River, Mount... establishing special local regulations on the waters of the Wando River and Cooper River in Mount Pleasant... River and Cooper River along the shoreline of Mount Pleasant, South Carolina. The Lowcountry Splash...

  17. Dialogic Cosmopolitanism and the New Wave of Movements: From Local Rupture to Global Openness

    DEFF Research Database (Denmark)

    Agustin, Oscar Garcia

    2017-01-01

    cosmopolitanism to account for the kind of cosmopolitanism which characterizes this new cycle. Being dialogic entails connectivity between previous and forthcoming struggles in a process combining determination and anticipation with the constant (re)definition of the movement. This process is considered...... to be the combination of social local ruptures with global openness. Dialogic cosmopolitanism consists of 3 main features: the conflictual dimension, whereby the dominant consensus is questioned and spaces of conflict and dissent are generated; the shaping of translocal solidarities that are able to connect local...

  18. iBILL: Using iBeacon and Inertial Sensors for Accurate Indoor Localization in Large Open Areas

    OpenAIRE

    Wu, Xudong; Shen, Ruofei; Fu, Luoyi; Tian, Xiaohua; Liu, Peng; Wang, Xinbing

    2017-01-01

    As a key technology that is widely adopted in location-based services (LBS), indoor localization has received considerable attention in both research and industrial areas. Despite the huge efforts made for localization using smartphone inertial sensors, its performance is still unsatisfactory in large open areas, such as halls, supermarkets, and museums, due to accumulated errors arising from the uncertainty of users’ mobility and fluctuations of magnetic field. Regarding that, this paper pre...

  19. MR imaging of the breast. Localization of focal breast lesions with the magnetom open at 0.2 T

    International Nuclear Information System (INIS)

    Sittek, H.; Perlet, C.; Herrmann, K.; Linsmeier, E.; Kessler, M.; Reiser, M.; Kolem, H.; Untch, M.

    1997-01-01

    Purpose: To answer the following questions: Whether reliable detection of lesions is possible in low-field-MRI-system (Magnetom Open 0.2 T) equipped with currently available hard- and software components in comparison to high field system (Magnetom Impact 1.0 T). Furthermore, whether localization of lesions suspect in MR-mammography can be realized in MR system of low field (Magnetom Open 0.2 T). Patients and Methods: In 11 patients, suspect lesions were diagnosed in diagnostic MR-mammography acquired with high field system (Magnetom Impact 1.0 T) and were compared to low field MR-mammographies of 0.2 T (Magnetom Open 0.2 T). In six of the 11 patients a suspect lesion was localized using wire marking. Results: All lesions considered suspect in diagnostic MR-mammography (Magnetom Impact 1.0 T) were also clearly identified in the 0.2 T system (Magnetom Open). In six cases wire marking was performed without any complications and with an accuracy of≤0.5 cm distance to the lesion. Conclusion: Although studies in the 0.2 T system clearly showed inferior SNR (34.6 vs. 83.1) and CNR (14.6 vs. 43.5) compared to studies with the high field system, all lesions considered suspect in diagnostic MR-mammography were reliably identified also in 0.2 T studies. Due to its open construction permitting permanent access to the breast and due to sufficient image quality, the Magnetom Open is suitable for interventions on the breast. (orig.) [de

  20. Impact of lengthening open water season on food security in Alaska coastal communities: Global impacts may outweigh local "frontline" effects

    Science.gov (United States)

    Rolph, R.; Mahoney, A. R.

    2015-12-01

    Using ice concentration data from the Alaska Sea Ice Atlas from 1953-2013 for selected communities in Alaska, we find a consistent trend toward later freeze up and earlier breakup, leading a lengthened open water period. Such changes are often considered to bring a variety of "frontline" local impacts to Arctic coastal communities such as increased rates of coastal erosion. However, direct consequences of these changes to local food security (e.g. through impacts on subsistence activities and marine transport of goods) may be outweighed at least in the short term by the effects of large scale Arctic sea ice change coupled with global oil markets. For example, a later freeze-up might delay local hunters' transition from boats to snow-machines, but whether this trend will affect hunting success, especially in the next few years, is uncertain. Likewise, the magnitude of change in open water season length is unlikely to be sufficient to increase the frequency with which communities are served by barges. However, an expanding open water season throughout the Arctic has implications for the global economy, which can have indirect effects on local communities. In the Chukchi and Beaufort Seas, where rapid sea ice change has been accompanied by increased interest in oil and gas development, the U.S. Bureau of Ocean Energy Management currently requires drilling operations to cease 38 days prior to freeze up. Taking this into account, the lengthening open water season has effectively extended the drilling season for oil companies by 184% since the 1950s. If oil development goes ahead, local communities will likely experience a range of indirect impacts on food security due to increased vessel traffic and demand on infrastructure coupled with changes in local economies and employment opportunities. Increased likelihood of an oil spill in coastal waters also poses a significant threat to local food security. Thus, while Arctic coastal communities are already experiencing

  1. Facilitation of Drug Transport across the Blood-Brain Barrier with Ultrasound and Microbubbles.

    Science.gov (United States)

    Meairs, Stephen

    2015-08-31

    Medical treatment options for central nervous system (CNS) diseases are limited due to the inability of most therapeutic agents to penetrate the blood-brain barrier (BBB). Although a variety of approaches have been investigated to open the BBB for facilitation of drug delivery, none has achieved clinical applicability. Mounting evidence suggests that ultrasound in combination with microbubbles might be useful for delivery of drugs to the brain through transient opening of the BBB. This technique offers a unique non-invasive avenue to deliver a wide range of drugs to the brain and promises to provide treatments for CNS disorders with the advantage of being able to target specific brain regions without unnecessary drug exposure. If this method could be applied for a range of different drugs, new CNS therapeutic strategies could emerge at an accelerated pace that is not currently possible in the field of drug discovery and development. This article reviews both the merits and potential risks of this new approach. It assesses methods used to verify disruption of the BBB with MRI and examines the results of studies aimed at elucidating the mechanisms of opening the BBB with ultrasound and microbubbles. Possible interactions of this novel delivery method with brain disease, as well as safety aspects of BBB disruption with ultrasound and microbubbles are addressed. Initial translational research for treatment of brain tumors and Alzheimer's disease is presented.

  2. Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model.

    Directory of Open Access Journals (Sweden)

    Habib Baghirov

    Full Text Available The treatment of brain diseases is hindered by the blood-brain barrier (BBB preventing most drugs from entering the brain. Focused ultrasound (FUS with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle-microbubbles and low-frequency FUS, and applied high-frequency FUS to generate acoustic radiation force and push nanoparticles through the extracellular matrix. Using confocal microscopy and image analysis, we quantified nanoparticle extravasation and distribution in the brain parenchyma. We also evaluated haemorrhage, as well as the expression of P-glycoprotein, a key BBB component. FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the distribution depended on the extent of BBB opening. The results from acoustic radiation force were not conclusive, but in a few animals some effect could be detected. P-glycoprotein was not significantly altered immediately after sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can achieve accumulation and displacement of nanoparticles in the brain parenchyma.

  3. Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model

    Science.gov (United States)

    Baghirov, Habib; Snipstad, Sofie; Sulheim, Einar; Berg, Sigrid; Hansen, Rune; Thorsen, Frits; Mørch, Yrr; Åslund, Andreas K. O.

    2018-01-01

    The treatment of brain diseases is hindered by the blood-brain barrier (BBB) preventing most drugs from entering the brain. Focused ultrasound (FUS) with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate) nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle-microbubbles and low-frequency FUS, and applied high-frequency FUS to generate acoustic radiation force and push nanoparticles through the extracellular matrix. Using confocal microscopy and image analysis, we quantified nanoparticle extravasation and distribution in the brain parenchyma. We also evaluated haemorrhage, as well as the expression of P-glycoprotein, a key BBB component. FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the distribution depended on the extent of BBB opening. The results from acoustic radiation force were not conclusive, but in a few animals some effect could be detected. P-glycoprotein was not significantly altered immediately after sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can achieve accumulation and displacement of nanoparticles in the brain parenchyma. PMID:29338016

  4. Identifying Socio-Cultural Factors That Impact the Use of Open Educational Resources in Local Public Administrations

    Directory of Open Access Journals (Sweden)

    Julia Stoffregen

    2016-12-01

    Full Text Available The goal of this paper is to define relevant barriers to the exchange of Open Educational Resources in local public administrations. Building upon a cultural model, eleven experts were interviewed and asked to evaluate several factors, such as openness in discourse, learning at the workplace, and superior support, among others. The result is a set of socio-cultural factors that shape the use of Open Educational Resources in public administrations. Significant factors are, in this respect, the independent choice of learning resources, the spirit of the platform, the range of available formats and access to technologies. Practitioners use these factors to elaborate on the readiness of public administrations towards the use of open e-Learning systems. To academic debates on culture in e-Learning, the results provide an alternative model that is contextualized to meet the demands of public sector contexts. Overall, the paper contributes to the lack of research about open e-Learning systems in the public sector, as well as regarding culture in the management of learning and knowledge exchange.

  5. Aristotle: A performance Impact Indicator for the OpenCL Kernels Using Local Memory

    Directory of Open Access Journals (Sweden)

    Jianbin Fang

    2014-01-01

    Full Text Available Due to the increasing complexity of multi/many-core architectures (with their mix of caches and scratch-pad memories and applications (with different memory access patterns, the performance of many workloads becomes increasingly variable. In this work, we address one of the main causes for this performance variability: the efficiency of the memory system. Specifically, based on an empirical evaluation driven by memory access patterns, we qualify and partially quantify the performance impact of using local memory in multi/many-core processors. To do so, we systematically describe memory access patterns (MAPs in an application-agnostic manner. Next, for each identified MAP, we use OpenCL (for portability reasons to generate two microbenchmarks: a “naive” version (without local memory and “an optimized” version (using local memory. We then evaluate both of them on typically used multi-core and many-core platforms, and we log their performance. What we eventually obtain is a local memory performance database, indexed by various MAPs and platforms. Further, we propose a set of composing rules for multiple MAPs. Thus, we can get an indicator of whether using local memory is beneficial in the presence of multiple memory access patterns. This indication can be used to either avoid the hassle of implementing optimizations with too little gain or, alternatively, give a rough prediction of the performance gain.

  6. Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer.

    Science.gov (United States)

    Papademetriou, Iason T; Porter, Tyrone

    2015-01-01

    Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood-brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers noninvasive delivery of small molecule and biological cancer therapeutics. Local delivery methods enable high dose delivery while avoiding systemic exposure. BBB disruption with focused ultrasound and microbubbles offers local and noninvasive treatment. Clinical trials show the prospects of these technologies and point to challenges for the future.

  7. Non-human primate skull effects on the cavitation detection threshold of FUS-induced blood-brain barrier opening

    Science.gov (United States)

    Wu, Shih-Ying; Tung, Yao-Sheng; Marquet, Fabrice; Chen, Cherry C.; Konofagou, Elisa E.

    2012-11-01

    Microbubble (MB)-assisted focused ultrasound is a promising technique for delivering drugs to the brain by noninvasively and transiently opening the blood-brain barrier (BBB), and monitoring BBB opening using passive cavitation detection (PCD) is critical in detecting its occurrence, extent as well as assessing its mechanism. One of the main obstacles in achieving those objectives in large animals is the transcranial attenuation. To study the effects, the cavitation response through the in-vitro non-human primate (NHP) skull was investigated. In-house manufactured lipid-shelled MB (medium diameter: 4-5 um) were injected into a 4-mm channel of a phantom below a degassed monkey skull. A hydrophone confocally aligned with the FUS transducer served as PCD during sonication (frequency: 0.50 MHz, peak rarefactional pressures: 0.05-0.60 MPa, pulse length: 100 cycles, PRF: 10 Hz, duration: 2 s) for four cases: water without skull, water with skull, MB without skull and MB with skull. A 5.1-MHz linear-array transducer was also used to monitor the MB disruption. The frequency spectra, spectrograms, stable cavitation dose (SCD) and inertial cavitation dose (ICD) were quantified. Results showed that the onset of stable cavitation and inertial cavitation in the experiments occurred at 50 kPa, and was detectable throught the NHP skull since the both the detection thresholds for stable cavitation and inertial cavitation remained unchanged compared to the non-skull case, and the SCD and ICD acquired transcranially may not adequately represent the true extent of stable and inertial cavitation due to the skull attenuation.

  8. Locality-Aware Task Scheduling and Data Distribution for OpenMP Programs on NUMA Systems and Manycore Processors

    Directory of Open Access Journals (Sweden)

    Ananya Muddukrishna

    2015-01-01

    Full Text Available Performance degradation due to nonuniform data access latencies has worsened on NUMA systems and can now be felt on-chip in manycore processors. Distributing data across NUMA nodes and manycore processor caches is necessary to reduce the impact of nonuniform latencies. However, techniques for distributing data are error-prone and fragile and require low-level architectural knowledge. Existing task scheduling policies favor quick load-balancing at the expense of locality and ignore NUMA node/manycore cache access latencies while scheduling. Locality-aware scheduling, in conjunction with or as a replacement for existing scheduling, is necessary to minimize NUMA effects and sustain performance. We present a data distribution and locality-aware scheduling technique for task-based OpenMP programs executing on NUMA systems and manycore processors. Our technique relieves the programmer from thinking of NUMA system/manycore processor architecture details by delegating data distribution to the runtime system and uses task data dependence information to guide the scheduling of OpenMP tasks to reduce data stall times. We demonstrate our technique on a four-socket AMD Opteron machine with eight NUMA nodes and on the TILEPro64 processor and identify that data distribution and locality-aware task scheduling improve performance up to 69% for scientific benchmarks compared to default policies and yet provide an architecture-oblivious approach for programmers.

  9. Characterizing Focused-Ultrasound Mediated Drug Delivery to the Heterogeneous Primate Brain In Vivo with Acoustic Monitoring

    Science.gov (United States)

    Wu, Shih-Ying; Sanchez, Carlos Sierra; Samiotaki, Gesthimani; Buch, Amanda; Ferrera, Vincent P.; Konofagou, Elisa E.

    2016-11-01

    Focused ultrasound with microbubbles has been used to noninvasively and selectively deliver pharmacological agents across the blood-brain barrier (BBB) for treating brain diseases. Acoustic cavitation monitoring could serve as an on-line tool to assess and control the treatment. While it demonstrated a strong correlation in small animals, its translation to primates remains in question due to the anatomically different and highly heterogeneous brain structures with gray and white matteras well as dense vasculature. In addition, the drug delivery efficiency and the BBB opening volume have never been shown to be predictable through cavitation monitoring in primates. This study aimed at determining how cavitation activity is correlated with the amount and concentration of gadolinium delivered through the BBB and its associated delivery efficiency as well as the BBB opening volume in non-human primates. Another important finding entails the effect of heterogeneous brain anatomy and vasculature of a primate brain, i.e., presence of large cerebral vessels, gray and white matter that will also affect the cavitation activity associated with variation of BBB opening in different tissue types, which is not typically observed in small animals. Both these new findings are critical in the primate brain and provide essential information for clinical applications.

  10. Facilitation of Drug Transport across the Blood–Brain Barrier with Ultrasound and Microbubbles

    Directory of Open Access Journals (Sweden)

    Stephen Meairs

    2015-08-01

    Full Text Available Medical treatment options for central nervous system (CNS diseases are limited due to the inability of most therapeutic agents to penetrate the blood–brain barrier (BBB. Although a variety of approaches have been investigated to open the BBB for facilitation of drug delivery, none has achieved clinical applicability. Mounting evidence suggests that ultrasound in combination with microbubbles might be useful for delivery of drugs to the brain through transient opening of the BBB. This technique offers a unique non-invasive avenue to deliver a wide range of drugs to the brain and promises to provide treatments for CNS disorders with the advantage of being able to target specific brain regions without unnecessary drug exposure. If this method could be applied for a range of different drugs, new CNS therapeutic strategies could emerge at an accelerated pace that is not currently possible in the field of drug discovery and development. This article reviews both the merits and potential risks of this new approach. It assesses methods used to verify disruption of the BBB with MRI and examines the results of studies aimed at elucidating the mechanisms of opening the BBB with ultrasound and microbubbles. Possible interactions of this novel delivery method with brain disease, as well as safety aspects of BBB disruption with ultrasound and microbubbles are addressed. Initial translational research for treatment of brain tumors and Alzheimer’s disease is presented.

  11. The interaction between the meningeal lymphatics and blood-brain barrier

    Science.gov (United States)

    Semyachkina-Glushkovskaya, O.; Abdurashitov, A.; Dubrovsky, A.; Pavlov, A.; Shushunova, N.; Maslyakova, G.; Navolokin, N.; Bucharskaya, A.; Tuchin, V.; Kurths, J.

    2018-02-01

    Here we show the interaction between the meningeal lymphatic system and the blood-brain barrier (BBB) function. In normal state, the meningeal lymphatic vessels are invisible on optical coherent tomography (OCT), while during the opening of the BBB, meningeal lymphatic vessels are clearly visualized by OCT in the area of cerebral venous sinuses. These results give a significant impulse in the new application of OCT for the study of physiology of meningeal lymphatic system as well as sheds light on novel strategies in the prognosis of the opening of the BBB related with many central nervous system diseases, such as stroke, brain trauma, Alzheimers disease, etc.

  12. Comparison of continuous interscalene block and subacromial infusion of local anesthetic for postoperative analgesia after open shoulder surgery.

    Science.gov (United States)

    Baskan, Semih; Cankaya, Deniz; Unal, Hidayet; Yoldas, Burak; Taspinar, Vildan; Deveci, Alper; Tabak, Yalcin; Baydar, Mustafa

    2017-01-01

    This study compared the efficacy of continuous interscalene block (CISB) and subacromial infusion of local anesthetic (CSIA) for postoperative analgesia after open shoulder surgery. This randomized, prospective, double-blinded, single-center study included 40 adult patients undergoing open shoulder surgery. All patients received a standardized general anesthetic. The patients were separated into group CISB and group CSIA. A loading dose of 40 mL 0.25% bupivacaine was administered and patient-controlled analgesia was applied by catheter with 0.1% bupivacaine 5 mL/h throughout 24 h basal infusion, 2 mL bolus dose, and 20 min knocked time in both groups postoperatively. Visual analog scale (VAS) scores, additional analgesia need, local anesthetic consumption, complications, and side effects were recorded during the first 24 h postoperatively. The range of motion (ROM) score was recorded preoperatively and in the first and third weeks postoperatively. A statistically significant difference was determined between the groups in respect of consumption of local anesthetic, VAS scores, additional analgesia consumption, complications, and side effects, with lower values recorded in the CISB group. There were no significant differences in ROM scoring in the preoperative and postoperative third week between the two groups but there were significant differences in ROM scoring in the postoperative first week, with higher ROM scoring values in the group CISB patients. The results of this study have shown that continuous interscalene infusion of bupivacaine is an effective and safe method of postoperative analgesia after open shoulder surgery.

  13. Preliminary studies of 99mTc-PQQ-NMDAR binding and effect of specificity binding by mannitol

    International Nuclear Information System (INIS)

    Xingqin Zhou; Yanyan Kong; Guoxian Cao; Jiankang Zhang

    2013-01-01

    Pyrroloquinoline quinone (PQQ) is a powerful neuroprotectant that specifically binds to brain NMDA receptors and inhibits excitotoxicity. Imaging this binding reaction in the brain remains a long sought goal in this field of study, and one of the primary challenges remaining is enabling soluble labeled PQQ to pass the blood-brain barrier (BBB). Previously, our group successfully labeled PQQ with Technetium-99m ( 99m Tc), a metastable nuclear isomer used in radioactive isotope medical tests. In this work, we determined the specific binding of 99m Tc-PQQ and NMDAR by radioligand receptor assay. Ebselen (EB) and MK-801 both effectively inhibited 99m Tc-PQQ binding. We then investigated methods of opening the BBB using mannitol to enable entry to the brain by 99m Tc-PQQ. Our results showed that 7.5 mL/kg of 20 % mannitol effectively opened the BBB and 20 min was the optimum treatment time. Competition studies showed that mannitol did not affect the specific binding between 99m Tc-PQQ and NMDA receptors. Using this method, the amount of 99m Tc-PQQ uptake and retention was increased most significantly in the hippocampus and cortex, and re-opening the BBB did not affect binding. Together, our results demonstrate that the use of mannitol to open the BBB may contribute significantly to improving image quality by increasing the uptake amount of a water-soluble agent in brain. (author)

  14. MR-guided preoperative localization and percutaneous core biopsy of suspicious breast lesions - experience on the vertically open 0.5 T system

    International Nuclear Information System (INIS)

    Schneider, J.P.; Schulz, T.; Rueger, S.; Schmidt, F.; Kahn, T.; Leinung, S.; Briest, S.

    2002-01-01

    Purpose. To evaluate the feasibility of performing breast interventions in a vertically open 0.5 T MR system (SIGNA SP/i, GE Medical Systems). To develop fitted equipment and to establish preoperative wire localization and percutaneous breast core biopsy as clinical routine procedures. Patients and methods. Initially, we applied a localization method with the patient placed in a sitting position in 31 cases using a single loop coil and a self-developed fixation device. Subsequently, 46 wire localizations and 28 percutaneous core biopsies were carried out in prone patient position using an open breast coil with an integrated biopsy device. The used instruments were either MR-compatible (18 G biopsy needle and localization wire, 14 G coaxial needle, prototype of a 16 G double-shoot gun) or MR-safe (double-shoot gun with 16 G needle). Results. After biopsy we found the needle tip (18 G for a wire localization and 14 G for a percutaneous core biopsy, respectively) placed either within or close to the lesions ( [de

  15. Relative importance of current and past landscape structure and local habitat conditions for plant species richness in dry grassland-like forest openings.

    Science.gov (United States)

    Husáková, Iveta; Münzbergová, Zuzana

    2014-01-01

    In fragmented landscapes, plant species richness may depend not only on local habitat conditions but also on landscape structure. In addition, both present and past landscape structure may be important for species richness. There are, however, only a few studies that have investigated the relative importance of all of these factors. The aim of this study was to examine the effect of current and past landscape structures and habitat conditions on species richness at dry grassland-like forest openings in a forested landscape and to assess their relative importance for species richness. We analyzed information on past and present landscape structures using aerial photographs from 1938, 1973, 1988, 2000 and 2007. We calculated the area of each locality and its isolation in the present and in the past and the continuity of localities in GIS. At each locality, we recorded all vascular plant species (296 species in 110 forest openings) and information on abiotic conditions of the localities. We found that the current species richness of the forest openings was significantly determined by local habitat conditions as well as by landscape structure in the present and in the past. The highest species richness was observed on larger and more heterogeneous localities with rocks and shallow soils, which were already large and well connected to other localities in 1938. The changes in the landscape structure in the past can thus have strong effects on current species richness. Future studies attempting to understand determinants of species diversity in fragmented landscapes should also include data on past landscape structure, as it may in fact be more important than the present structure.

  16. The Challenge of Prenatal Diagnostic Work-Up of Maternally Inherited X-Linked Opitz G/BBB: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Marialuigia Spinelli

    2015-01-01

    Full Text Available Background. Prenatal diagnosis of Optiz G/BBB syndrome (OS is challenging because the characteristic clinical features, such as facial and genitourinary anomalies, may be subtle at sonography and rather unspecific. Furthermore, molecular testing of the disease gene is not routinely performed, unless a specific diagnosis is suggested. Method. Both familial and ultrasound data were used to achieve the diagnosis of X-linked OS (XLOS, which was confirmed by molecular testing of MID1 gene (Xp22.3 at birth. Results. Sequencing of MID1 gene disclosed the nucleotide change c.1285 +1 G>T, previously associated with XLOS. Conclusions. This case illustrates current challenges of the prenatal diagnostic work-up of XLOS and exemplifies how clinical investigation, including family history, and accurate US foetal investigations can lead to the correct diagnosis.

  17. Motion of isolated open vortex filaments evolving under the truncated local induction approximation

    Science.gov (United States)

    Van Gorder, Robert A.

    2017-11-01

    The study of nonlinear waves along open vortex filaments continues to be an area of active research. While the local induction approximation (LIA) is attractive due to locality compared with the non-local Biot-Savart formulation, it has been argued that LIA appears too simple to model some relevant features of Kelvin wave dynamics, such as Kelvin wave energy transfer. Such transfer of energy is not feasible under the LIA due to integrability, so in order to obtain a non-integrable model, a truncated LIA, which breaks the integrability of the classical LIA, has been proposed as a candidate model with which to study such dynamics. Recently Laurie et al. ["Interaction of Kelvin waves and nonlocality of energy transfer in superfluids," Phys. Rev. B 81, 104526 (2010)] derived truncated LIA systematically from Biot-Savart dynamics. The focus of the present paper is to study the dynamics of a section of common open vortex filaments under the truncated LIA dynamics. We obtain the analog of helical, planar, and more general filaments which rotate without a change in form in the classical LIA, demonstrating that while quantitative differences do exist, qualitatively such solutions still exist under the truncated LIA. Conversely, solitons and breather solutions found under the LIA should not be expected under the truncated LIA, as the existence of such solutions relies on the existence of an infinite number of conservation laws which is violated due to loss of integrability. On the other hand, similarity solutions under the truncated LIA can be quite different to their counterparts found for the classical LIA, as they must obey a t1/3 type scaling rather than the t1/2 type scaling commonly found in the LIA and Biot-Savart dynamics. This change in similarity scaling means that Kelvin waves are radiated at a slower rate from vortex kinks formed after reconnection events. The loss of soliton solutions and the difference in similarity scaling indicate that dynamics emergent under

  18. The Fault Detection, Localization, and Tolerant Operation of Modular Multilevel Converters with an Insulated Gate Bipolar Transistor (IGBT Open Circuit Fault

    Directory of Open Access Journals (Sweden)

    Wei Li

    2018-04-01

    Full Text Available Reliability is one of the critical issues for a modular multilevel converter (MMC since it consists of a large number of series-connected power electronics submodules (SMs. In this paper, a complete control strategy including fault detection, localization, and tolerant operation is proposed for the MMC under an insulated gate bipolar transistor (IGBT open circuit fault. According to the output characteristics of the SM with the open-circuit fault of IGBT, a fault detection method based on the circulating current and output current observation is used. In order to further precisely locate the position of the faulty SM, a fault localization method based on the SM capacitor voltage observation is developed. After the faulty SM is isolated, the continuous operation of the converter is ensured by adopting the fault-tolerant strategy based on the use of redundant modules. To verify the proposed fault detection, fault localization, and fault-tolerant operation strategies, a 900 kVA MMC system under the conditions of an IGBT open circuit is developed in the Matlab/Simulink platform. The capabilities of rapid detection, precise positioning, and fault-tolerant operation of the investigated detection and control algorithms are also demonstrated.

  19. Openness to change: experiential and demographic components of change in in Local Health Department leaders

    Directory of Open Access Journals (Sweden)

    Emmanuel D Jadhav

    2015-09-01

    Full Text Available Background: During the 2008-10 economic recession, Kentucky local health department (LHD leaders utilized innovative strategies to maintain their programs. A characteristic of innovative strategy is leader openness to change. Leader demographical research in for-profit organizations has yielded valuable insight into leader openness to change. For LHD leaders the nature of the association between leader demographic and organizational characteristics on leader openness to change is unknown. The objectives of this study are to identify variation in openness to change by leaders’ demographic and organizational characteristics and to characterize the underlying relationships. Material and Methods: The study utilized Spearman rank correlations test to determine relationships between leader openness to change (ACQ and leader and LHD characteristics. To identify differences in the distribution of ACQ scores, Wilcoxon-Mann-Whitney and Kruskal Wallis non-parametric tests were used, and to adjust for potential confounding linear regression analysis was performed.Data: LHD leaders in the Commonwealth of Kentucky were the unit of analysis. Expenditure and revenue data were available from the state health department. National census data was utilized for county level population estimates. A cross-sectional survey was performed of KY LHD leaders’ observable attributes relating to age, gender, race, educational background, leadership experience and openness to change. Results: Leaders had relatively high openness to change scores. Spearman correlations between leader ACQ and departmental 2012-13 revenue and expenditures were statistically significant, as were the differences observed in ACQ by gender and the educational level of the leader. Differences in ACQ score by education level and agency revenue were significant even after adjusting for potential confounders. The analyses imply there are underlying relationships between leader and LHD characteristics

  20. Effect of chronic hypoglycaemia on glucose concentration and glycogen content in rat brain: a localized 13C NMR study

    OpenAIRE

    Lei, Hongxia; Gruetter, Rolf

    2006-01-01

    While chronic hypoglycaemia has been reported to increase unidirectional glucose transport across the blood-brain barrier (BBB) and to increase GLUT1 expression at the endothelium, the effect on steady-state brain d-glucose and brain glycogen content is currently unknown. Brain glucose and glycogen concentrations were directly measured in vivo using localized 13C magnetic resonance spectroscopy (MRS) following 12-14 days of hypoglycaemia. Brain glucose content was significantly increased by 4...

  1. Open Data as Open Educational Resources: Case studies of emerging practice

    OpenAIRE

    Atenas, Javiera; Havemann, Leo

    2018-01-01

    This collection presents the stories of our contributors’ experiences and insights, in order to demonstrate the enormous potential for openly-licensed and accessible datasets (Open Data) to be used as Open Educational Resources (OER). Open Data is an umbrella term describing openly-licensed, interoperable, and reusable datasets which have been created and made available to the public by national or local governments, academic researchers, or other organisations. These datasets can be accessed...

  2. Estimating blood and brain concentrations and blood-to-brain influx by magnetic resonance imaging with step-down infusion of Gd-DTPA in focal transient cerebral ischemia and confirmation by quantitative autoradiography with Gd-[14C]DTPA

    OpenAIRE

    Knight, Robert A; Karki, Kishor; Ewing, James R; Divine, George W; Fenstermacher, Joseph D; Patlak, Clifford S; Nagaraja, Tavarekere N

    2009-01-01

    An intravenous step-down infusion procedure that maintained a constant gadolinium-diethylene-triaminepentaacetic acid (Gd-DTPA) blood concentration and magnetic resonance imaging (MRI) were used to localize and quantify the blood–brain barrier (BBB) opening in a rat model of transient cerebral ischemia (n = 7). Blood-to-brain influx rate constant (Ki) values of Gd-DTPA from such regions were estimated using MRI–Patlak plots and compared with the Ki values of Gd-[14C]DTPA, determined minutes l...

  3. Topological open string amplitudes on local toric del Pezzo surfaces via remodeling the B-model

    International Nuclear Information System (INIS)

    Manabe, Masahide

    2009-01-01

    We study topological strings on local toric del Pezzo surfaces by a method called remodeling the B-model which was recently proposed by Bouchard, Klemm, Marino and Pasquetti. For a large class of local toric del Pezzo surfaces we prove a functional formula of the Bergman kernel which is the basic constituent of the topological string amplitudes by the topological recursion relation of Eynard and Orantin. Because this formula is written as a functional of the period, we can obtain the topological string amplitudes at any point of the moduli space by a simple change of variables of the Picard-Fuchs equations for the period. By this formula and mirror symmetry we compute the A-model amplitudes on K F 2 , and predict the open orbifold Gromov-Witten invariants of C 3 /Z 4 .

  4. Local anesthetic effect of docosahexaenoic acid on the nociceptive jaw-opening reflex in rats.

    Science.gov (United States)

    Mitome, Kazuki; Takehana, Shiori; Oshima, Katsuo; Shimazu, Yoshihito; Takeda, Mamoru

    2018-02-23

    Although docosahexaenoic acid (DHA) administration suppresses sodium channels in primary afferent sensory neurons, the acute local effect of DHA on the trigeminal nociceptive reflex remains to be elucidated, in vivo. Therefore, the aim of the present study was to investigate whether local administration of DHA attenuates the nociceptive jaw-opening reflex (JOR) in vivo in the rat. The JOR evoked by electrical stimulation of the tongue was recorded by a digastric muscle electromyogram (dEMG) in pentobarbital-anesthetized rats. The amplitude of the dEMG response was significantly increased in proportion to the electrical stimulation intensity (1-5 x threshold). At 3 x threshold, local administration of DHA (0.1, 10 and 25 mM) dose-dependently inhibited the dEMG response, and lasted 40 min. Maximum inhibition of the dEMG signal amplitude was seen within approximately 10 min. The mean magnitude of inhibition of the dEMG signal amplitude by DHA (25 mM) was almost equal to the local anesthetic, 1% lidocaine (37 mM), a sodium channel blocker. These findings suggest that DHA attenuates the nociceptive JOR via possibly blocking sodium channels, and strongly support the idea that DHA is a potential therapeutic agent and complementary alternative medicine for the prevention of acute trigeminal nociception. Copyright © 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

  5. PLGA nanoparticles modified with a BBB-penetrating peptide co-delivering Aβ generation inhibitor and curcumin attenuate memory deficits and neuropathology in Alzheimer's disease mice.

    Science.gov (United States)

    Huang, Na; Lu, Shuai; Liu, Xiao-Ge; Zhu, Jie; Wang, Yu-Jiong; Liu, Rui-Tian

    2017-10-06

    Alzheimer's disease (AD) is the most common form of dementia, characterized by the formation of extracellular senile plaques and neuronal loss caused by amyloid β (Aβ) aggregates in the brains of AD patients. Conventional strategies failed to treat AD in clinical trials, partly due to the poor solubility, low bioavailability and ineffectiveness of the tested drugs to cross the blood-brain barrier (BBB). Moreover, AD is a complex, multifactorial neurodegenerative disease; one-target strategies may be insufficient to prevent the processes of AD. Here, we designed novel kind of poly(lactide-co-glycolic acid) (PLGA) nanoparticles by loading with Aβ generation inhibitor S1 (PQVGHL peptide) and curcumin to target the detrimental factors in AD development and by conjugating with brain targeting peptide CRT (cyclic CRTIGPSVC peptide), an iron-mimic peptide that targets transferrin receptor (TfR), to improve BBB penetration. The average particle size of drug-loaded PLGA nanoparticles and CRT-conjugated PLGA nanoparticles were 128.6 nm and 139.8 nm, respectively. The results of Y-maze and new object recognition test demonstrated that our PLGA nanoparticles significantly improved the spatial memory and recognition in transgenic AD mice. Moreover, PLGA nanoparticles remarkably decreased the level of Aβ, reactive oxygen species (ROS), TNF-α and IL-6, and enhanced the activities of super oxide dismutase (SOD) and synapse numbers in the AD mouse brains. Compared with other PLGA nanoparticles, CRT peptide modified-PLGA nanoparticles co-delivering S1 and curcumin exhibited most beneficial effect on the treatment of AD mice, suggesting that conjugated CRT peptide, and encapsulated S1 and curcumin exerted their corresponding functions for the treatment.

  6. An Open Pit Nanofluidic Tool: Localized Chemistry Assisted by Mesoporous Thin Film Infiltration.

    Science.gov (United States)

    Mercuri, Magalí; Pierpauli, Karina A; Berli, Claudio L A; Bellino, Martín G

    2017-05-17

    Nanofluidics based on nanoscopic porous structures has emerged as the next evolutionary milestone in the construction of versatile nanodevices with unprecedented applications. However, the straightforward development of nanofluidically interconnected systems is crucial for the production of practical devices. Here, we demonstrate that spontaneous infiltration into supramolecularly templated mesoporous oxide films at the edge of a sessile drop in open air can be used to connect pairs of landmarks. The liquids from the drops can then join through the nanoporous network to guide a localized chemical reaction at the nanofluid-front interface. This method, here named "open-pit" nanofluidics, allows mixing reagents from nanofluidically connected droplet reservoirs that can be used as reactors to conduct reactions and precipitation processes. From the fundamental point of view, the work contributes to unveiling subtle phenomena during spontaneous infiltration of fluids in bodies with nanoscale dimensions such as the front broadening effect and the oscillatory behavior of the infiltration-evaporation front. The approach has distinctive advantages such as easy fabrication, low cost, and facility of scaling up for future development of ultrasensitive detection, controlled nanomaterial synthesis, and novel patterning methods.

  7. Evaluating organ delineation, dose calculation and daily localization in an open-MRI simulation workflow for prostate cancer patients

    International Nuclear Information System (INIS)

    Doemer, Anthony; Chetty, Indrin J; Glide-Hurst, Carri; Nurushev, Teamour; Hearshen, David; Pantelic, Milan; Traughber, Melanie; Kim, Joshua; Levin, Kenneth; Elshaikh, Mohamed A; Walker, Eleanor; Movsas, Benjamin

    2015-01-01

    This study describes initial testing and evaluation of a vertical-field open Magnetic Resonance Imaging (MRI) scanner for the purpose of simulation in radiation therapy for prostate cancer. We have evaluated the clinical workflow of using open MRI as a sole modality for simulation and planning. Relevant results related to MRI alignment (vs. CT) reference dataset with Cone-Beam CT (CBCT) for daily localization are presented. Ten patients participated in an IRB approved study utilizing MRI along with CT simulation with the intent of evaluating the MRI-simulation process. Differences in prostate gland volume, seminal vesicles, and penile bulb were assessed with MRI and compared to CT. To evaluate dose calculation accuracy, bulk-density-assignments were mapped onto respective MRI datasets and treated IMRT plans were re-calculated. For image localization purposes, 400 CBCTs were re-evaluated with MRI as the reference dataset and daily shifts compared against CBCT-to-CT registration. Planning margins based on MRI/CBCT shifts were computed using the van Herk formalism. Significant organ contour differences were noted between MRI and CT. Prostate volumes were on average 39.7% (p = 0.002) larger on CT than MRI. No significant difference was found in seminal vesicle volumes (p = 0.454). Penile bulb volumes were 61.1% higher on CT, without statistical significance (p = 0.074). MRI-based dose calculations with assigned bulk densities produced agreement within 1% with heterogeneity corrected CT calculations. The differences in shift positions for the cohort between CBCT-to-CT registration and CBCT-to-MRI registration are −0.15 ± 0.25 cm (anterior-posterior), 0.05 ± 0.19 cm (superior-inferior), and −0.01 ± 0.14 cm (left-right). This study confirms the potential of using an open-field MRI scanner as primary imaging modality for prostate cancer treatment planning simulation, dose calculations and daily image localization

  8. Local-global knowledge sourcing in the context of an open innovation knowledge platform : the case of Amsterdam Denim City

    NARCIS (Netherlands)

    DiVito, Lori; Ingen-Housz, Zita

    2016-01-01

    Our paper investigates the inherent tensions between the local embeddedness of highly tacit knowledge and the global sourcing of ‘open’ knowledge or innovation. A single case study design enabled us to perform a thorough and detailed analysis of inter-firm collaboration and open innovation within

  9. BNCT of intracerebral melanoma. Enhanced survival and cure following Cereport mediated opening of the blood-brain barrier

    International Nuclear Information System (INIS)

    Barth, R.F.; Yang, W.; Bartus, R.T.; Rotaru, J.H.; Ferketich, A.K.; Moeschberger, M.L.; Nawrocky, M.M.; Coderre, J.A.

    2000-01-01

    Cereport is a bradykinin analogue that produces a transient, pharmacologically mediated opening of the blood-brain barrier (BBB). The present study was designed to determine if Cereport could enhance the delivery of BPA and the efficacy of BNCT in nude rats bearing intracerebral implants of the human MRA 27 melanoma. Animals that received intracarotid (i.c.) injection of Cereport and i.c. BPA had a mean survival time of 115 d compared to 82 d without Cereport, 42 d for i.v. BPA with Cereport and 31 d for irradiated controls. The combination of i.c. Cereport and BPA produced a 400% increase in the life span with 35% long-term survivors (>180 d). (author)

  10. Assessment of Blood-Brain Barrier Permeability by Dynamic Contrast-Enhanced MRI in Transient Middle Cerebral Artery Occlusion Model after Localized Brain Cooling in Rats

    International Nuclear Information System (INIS)

    Kim, Eun Soo; Lee, Seung-Koo; Kwon, Mi Jung; Lee, Phil Hye; Ju, Young-Su; Yoon, Dae Young; Kim, Hye Jeong; Lee, Kwan Seop

    2016-01-01

    The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20℃) infusion group, and localized warm-saline (37℃) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min -1 vs. 0.07 ± 0.02 min -1 , p = 0.661 for K trans ; 0.30 ± 0.05 min -1 vs. 0.37 ± 0.11 min -1 , p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Localized brain cooling (20℃) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37℃) infusion group

  11. Assessment of blood-brain barrier permeability by dynamic contrast-enhanced MRI in transient middle cerebral artery occlusion model after localized brain cooling in rats

    International Nuclear Information System (INIS)

    Kim, Eun Soo; Lee, Kwan Seop; Kwon, Mi Jung; Ju, Young Su; Lee, Seung Koo; Lee, Phil Hye; Yoon, Dae Young; Kim, Hye Jeong

    2016-01-01

    The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20 .deg. ) infusion group, and localized warm-saline (37 .deg. ) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min -1 vs. 0.07 ± 0.02 min -1 ,p = 0.661 for K trans ; 0.30 ± 0.05 min -1 vs. 0.37 ± 0.11 min -1 ,p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Localized brain cooling (20 .deg. ) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37 .deg. ) infusion group

  12. Feasibility and Safety of Intra-arterial Pericyte Progenitor Cell Delivery Following Mannitol-Induced Transient Blood-Brain Barrier Opening in a Canine Model.

    Science.gov (United States)

    Youn, Sung Won; Jung, Keun-Hwa; Chu, Kon; Lee, Jong-Young; Lee, Soon-Tae; Bahn, Jae-jun; Park, Dong-Kyu; Yu, Jung-Suk; Kim, So-Yun; Kim, Manho; Lee, Sang Kun; Han, Moon-Hee; Roh, Jae-Kyu

    2015-01-01

    Stem cell therapy is currently being studied with a view to rescuing various neurological diseases. Such studies require not only the discovery of potent candidate cells but also the development of methods that allow optimal delivery of those candidates to the brain tissues. Given that the blood-brain barrier (BBB) precludes cells from entering the brain, the present study was designed to test whether hyperosmolar mannitol securely opens the BBB and enhances intra-arterial cell delivery. A noninjured normal canine model in which the BBB was presumed to be closed was used to evaluate the feasibility and safety of the tested protocol. Autologous adipose tissue-derived pericytes with platelet-derived growth factor receptor β positivity were utilized. Cells were administered 5 min after mannitol pretreatment using one of following techniques: (1) bolus injection of a concentrated suspension, (2) continuous infusion of a diluted suspension, or (3) bolus injection of a concentrated suspension that had been shaken by repeated syringe pumping. Animals administered a concentrated cell suspension without mannitol pretreatment served as a control group. Vital signs, blood parameters, neurologic status, and major artery patency were kept stable throughout the experiment and the 1-month posttreatment period. Although ischemic lesions were noted on magnetic resonance imaging in several mongrel dogs with concentrated cell suspension, the injection technique using repeated syringe shaking could avert this complication. The cells were detected in both ipsilateral and contralateral cortices and were more frequent at the ipsilateral and frontal locations, whereas very few cells were observed anywhere in the brain when mannitol was not preinjected. These data suggest that intra-arterial cell infusion with mannitol pretreatment is a feasible and safe therapeutic approach in stable brain diseases such as chronic stroke.

  13. Rupture prediction for induction bends under opening mode bending with emphasis on strain localization

    International Nuclear Information System (INIS)

    Mitsuya, Masaki; Sakanoue, Takashi

    2015-01-01

    This study focuses on the opening mode of induction bends; this mode represents the deformation outside a bend. Bending experiments on induction bends are shown and the manner of failure of these bends was investigated. Ruptures occur at the intrados of the bends, which undergo tensile stress, and accompany the local reduction of wall thickness, i.e., necking that indicates strain localization. By implementing finite element analysis (FEA), it was shown that the rupture is dominated not by the fracture criterion of material but by the initiation of strain localization that is a deformation characteristic of the material. These ruptures are due to the rapid increase of local strain after the initiation of strain localization and suddenly reach the fracture criterion. For the evaluation of the deformability of the bends, a method based on FEA that can predict the displacement at the rupture is proposed. We show that the yield surface shape and the true stress–strain relationship after uniform elongation have to be defined on the basis of the actual properties of the bend material. The von Mises yield criterion, which is commonly used in cases of elastic–plastic FEA, could not predict the rupture and overestimated the deformability. In contrast, a yield surface obtained by performing tensile tests on a biaxial specimen could predict the rupture. The prediction of the rupture was accomplished by an inverse calibration method that determined the true stress-strain relationship after uniform elongation. As an alternative to the inverse calibration, a simple extrapolation method of the true stress-strain relationship after uniform elongation which can predict the rupture is proposed. - Highlights: • A method based on FEA that can predict the displacement at the rupture is proposed. • The yield surface shape and the true stress–strain have to be defined precisely. • The von Mises yield criterion overestimated the deformability. • The ruptures are due to the

  14. Three-Dimensional Blood-Brain Barrier Model for in vitro Studies of Neurovascular Pathology

    Science.gov (United States)

    Cho, Hansang; Seo, Ji Hae; Wong, Keith H. K.; Terasaki, Yasukazu; Park, Joseph; Bong, Kiwan; Arai, Ken; Lo, Eng H.; Irimia, Daniel

    2015-10-01

    Blood-brain barrier (BBB) pathology leads to neurovascular disorders and is an important target for therapies. However, the study of BBB pathology is difficult in the absence of models that are simple and relevant. In vivo animal models are highly relevant, however they are hampered by complex, multi-cellular interactions that are difficult to decouple. In vitro models of BBB are simpler, however they have limited functionality and relevance to disease processes. To address these limitations, we developed a 3-dimensional (3D) model of BBB on a microfluidic platform. We verified the tightness of the BBB by showing its ability to reduce the leakage of dyes and to block the transmigration of immune cells towards chemoattractants. Moreover, we verified the localization at endothelial cell boundaries of ZO-1 and VE-Cadherin, two components of tight and adherens junctions. To validate the functionality of the BBB model, we probed its disruption by neuro-inflammation mediators and ischemic conditions and measured the protective function of antioxidant and ROCK-inhibitor treatments. Overall, our 3D BBB model provides a robust platform, adequate for detailed functional studies of BBB and for the screening of BBB-targeting drugs in neurological diseases.

  15. Open Data for Territorial Specialization Assessment Territorial Specialization in Attracting Local Development Funds: an Assessment. Procedure Based on Open Data and Open Tools

    Directory of Open Access Journals (Sweden)

    Giuseppe Las Casas

    2014-05-01

    Full Text Available The New Cohesion Policy opens to an integrated place-based approach for the improvement of territorial and social cohesion. The issue of territorial impact assessment of regional development policies highlight that data availability, open access to datasets in “near real-time”, participation, knowledge sharing, assumed importance within the development planning process. The contribution of ‘open data’ appears to be mature and in this paper we present an application of spatial analysis techniques for the evaluation of spatial effects of EU funds starting form open data by open-coesione. The application regards an internal areas of Basilicata Region: the Agri Valley. A complex contests in which an environmental and agricultural traditional vocation conflicts with a recent development of oil extraction industries. Conclusions regard further applications and perspectives for improving and supporting regional development planning considering the exploitation of open data sources and spatial analysis.

  16. Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer

    OpenAIRE

    Papademetriou, Iason T; Porter, Tyrone

    2015-01-01

    Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood–brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers non...

  17. Dynamic provisioning of local and remote compute resources with OpenStack

    Science.gov (United States)

    Giffels, M.; Hauth, T.; Polgart, F.; Quast, G.

    2015-12-01

    Modern high-energy physics experiments rely on the extensive usage of computing resources, both for the reconstruction of measured events as well as for Monte-Carlo simulation. The Institut fur Experimentelle Kernphysik (EKP) at KIT is participating in both the CMS and Belle experiments with computing and storage resources. In the upcoming years, these requirements are expected to increase due to growing amount of recorded data and the rise in complexity of the simulated events. It is therefore essential to increase the available computing capabilities by tapping into all resource pools. At the EKP institute, powerful desktop machines are available to users. Due to the multi-core nature of modern CPUs, vast amounts of CPU time are not utilized by common desktop usage patterns. Other important providers of compute capabilities are classical HPC data centers at universities or national research centers. Due to the shared nature of these installations, the standardized software stack required by HEP applications cannot be installed. A viable way to overcome this constraint and offer a standardized software environment in a transparent manner is the usage of virtualization technologies. The OpenStack project has become a widely adopted solution to virtualize hardware and offer additional services like storage and virtual machine management. This contribution will report on the incorporation of the institute's desktop machines into a private OpenStack Cloud. The additional compute resources provisioned via the virtual machines have been used for Monte-Carlo simulation and data analysis. Furthermore, a concept to integrate shared, remote HPC centers into regular HEP job workflows will be presented. In this approach, local and remote resources are merged to form a uniform, virtual compute cluster with a single point-of-entry for the user. Evaluations of the performance and stability of this setup and operational experiences will be discussed.

  18. Three Paths to Better Tyrosine Kinase Inhibition Behind the Blood-Brain Barrier in Treating Chronic Myelogenous Leukemia and Glioblastoma with Imatinib

    Science.gov (United States)

    Kast, Richard E; Focosi, Daniele

    2010-01-01

    Chronic myelogenous leukemia (CML) can be controlled for years with the tyrosine kinase inhibitor imatinib but because imatinib poorly penetrates the blood-brain barrier (BBB), on occasion, the CML clone will thrive and evolve to an accelerated phase in the resulting imatinib sanctuary within the central nervous system. In this, CML resembles glioblastoma in that imatinib, which otherwise may be effective, cannot get to the tumor. Although a common street drug of abuse, methamphetamine is Food and Drug Administration-approved and marketed as a pharmaceutical drug to treat attention-deficit disorders. It has shown the ability to open the BBB in rodents. We have some clinical hints that it may do so in humans as well. This short note presents three new points potentially leading to better tyrosine kinase inhibition behind the BBB: 1) Pharmaceutical methamphetamine may have a useful role in treating both CML and glioblastoma by allowing higher imatinib concentrations behind the BBB. 2) The old antidepressant and monoamine oxidase inhibitor selegiline, used to treat Parkinson disease, is catabolized to methamphetamine. Selegiline, as a nonscheduled drug,may therefore be an easier way to open the BBB, allowing more effective chemotherapy with tyrosine kinases. 3) Dasatinib is a tyrosine kinase inhibitor with a spectrum of inhibition only partially overlapping that of imatinib and a mechanism of tyrosine kinase inhibition that is different from that of imatinib. The two should be additive. In addition, dasatinib crosses the BBB poorly, and it can therefore be expected to benefit from methamphetamine-assisted entry. PMID:20165690

  19. Targeted Gene Transfer to the Brain via the Delivery of Brain-Penetrating DNA Nanoparticles with Focused Ultrasound

    Science.gov (United States)

    Mead, Brian P.; Mastorakos, Panagiotis; Suk, Jung Soo; Klibanov, Alexander L.; Hanes, Justin; Price, Richard J.

    2016-01-01

    Gene therapy holds promise for the treatment of many pathologies of the central nervous system (CNS), including brain tumors and neurodegenerative diseases. However, the delivery of systemically administered gene carriers to the CNS is hindered by both the blood-brain barrier (BBB) and the nanoporous and electrostatically charged brain extracelluar matrix (ECM), which acts as a steric and adhesive barrier. We have previously shown that these physiological barriers may be overcome by, respectively, opening the BBB with MR image-guided focused ultrasound (FUS) and microbubbles and using highly compact “brain penetrating” nanoparticles (BPN) coated with a dense polyethylene glycol corona that prevents adhesion to ECM components. Here, we tested whether this combined approach could be utilized to deliver systemically administered DNA-bearing BPN (DNA-BPN) across the BBB and mediate localized, robust, and sustained transgene expression in the rat brain. Systemically administered DNA-BPN delivered through the BBB with FUS led to dose-dependent transgene expression only in the FUS-treated region that was evident as early as 24 h post administration and lasted for at least 28 days. In the FUS-treated region ~42% of all cells, including neurons and astrocytes, were transfected, while less than 6% were transfected in the contralateral non-FUS treated hemisphere. Importantly, this was achieved without any sign of toxicity or astrocyte activation. We conclude that the image-guided delivery of DNA-BPN with FUS and microbubbles constitutes a safe and non-invasive strategy for targeted gene therapy to the brain. PMID:26732553

  20. Transport of Poly(n-butylcyano-acrylate) nanoparticles across the blood-brain barrier in vitro and their influence on barrier integrity

    Energy Technology Data Exchange (ETDEWEB)

    Rempe, Ralf; Cramer, Sandra; Huewel, Sabine [Department of Biochemistry, University of Muenster, Wilhelm-Klemm-Strasse 2, D-48149 Muenster (Germany); Galla, Hans-Joachim, E-mail: gallah@uni-muenster.de [Department of Biochemistry, University of Muenster, Wilhelm-Klemm-Strasse 2, D-48149 Muenster (Germany)

    2011-03-04

    Research highlights: {yields} Poly(n-butylcyano-acrylate) (PBCA) nanoparticles may be promising drug carriers. {yields} Influence of PBCA nanoparticles on the integrity of the blood-brain barrier in vitro. {yields} PBCA nanoparticles lead to a reversible disruption of the BBB in vitro after 4 h. {yields} Potential application as time-dependent and specific opener of the BBB. -- Abstract: In previous studies it was shown that polysorbate 80(PS80)-coated poly(n-butylcyano-acrylate) nanoparticles (PBCA-NP) are able to cross the blood-brain barrier (BBB) in vitro and in vivo. In order to explore and extend the potential applications of PBCA-NP as drug carriers, it is important to ascertain their effect on the BBB. The objective of the present study was to determine the effect of PS80-coated PBCA-NP on the BBB integrity of a porcine in vitro model. This has been investigated by monitoring the development of the transendothelial electrical resistance (TEER) after the addition of PBCA-NP employing impedance spectroscopy. Additionally, the integrity of the BBB in vitro was verified by measuring the passage of the reference substances {sup 14}C-sucrose and FITC-BSA after addition of PBCA-NP. In this study we will show that the application of PS80-coated PBCA-NP leads to a reversible disruption of the barrier after 4 h. The observed disruption of the barrier could also be confirmed by {sup 14}C-sucrose and FITC-BSA permeability studies. Comparing the TEER and permeability studies the lowest resistances and maximal values for permeabilities were both observed after 4 h. These results indicate that PS80-coated PBCA-NP might be suitable for the use as drug carriers. The reversible disruption also offers the possibility to use these particles as specific opener of the BBB. Instead of incorporating the therapeutic agents into the NP, the drugs may cross the BBB after being applied simultaneously with the PBCA-NP.

  1. Open Source Communities in Technical Writing: Local Exigence, Global Extensibility

    Science.gov (United States)

    Conner, Trey; Gresham, Morgan; McCracken, Jill

    2011-01-01

    By offering open-source software (OSS)-based networks as an affordable technology alternative, we partnered with a nonprofit community organization. In this article, we narrate the client-based experiences of this partnership, highlighting the ways in which OSS and open-source culture (OSC) transformed our students' and our own expectations of…

  2. Assessment of Blood-Brain Barrier Permeability by Dynamic Contrast-Enhanced MRI in Transient Middle Cerebral Artery Occlusion Model after Localized Brain Cooling in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Soo [Department of Radiology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068 (Korea, Republic of); Lee, Seung-Koo [Department of Radiology, Yonsei University College of Medicine, Seoul 03722 (Korea, Republic of); Kwon, Mi Jung [Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068 (Korea, Republic of); Lee, Phil Hye [Department of Neurology, Yonsei University College of Medicine, Seoul 03722 (Korea, Republic of); Ju, Young-Su [Department of Industrial Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068 (Korea, Republic of); Yoon, Dae Young [Department of Radiology, Hallym University Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 05355 (Korea, Republic of); Kim, Hye Jeong [Department of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 07441 (Korea, Republic of); Lee, Kwan Seop [Department of Radiology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068 (Korea, Republic of)

    2016-11-01

    The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20℃) infusion group, and localized warm-saline (37℃) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min{sup -1} vs. 0.07 ± 0.02 min{sup -1}, p = 0.661 for K{sup trans}; 0.30 ± 0.05 min{sup -1} vs. 0.37 ± 0.11 min{sup -1}, p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Localized brain cooling (20℃) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37℃) infusion group.

  3. Assessment of blood-brain barrier permeability by dynamic contrast-enhanced MRI in transient middle cerebral artery occlusion model after localized brain cooling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Soo; Lee, Kwan Seop; Kwon, Mi Jung; Ju, Young Su [Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang (Korea, Republic of); Lee, Seung Koo; Lee, Phil Hye [Yonsei University College of Medicine, Seoul (Korea, Republic of); Yoon, Dae Young [Dept. of Radiology, Hallym University Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul (Korea, Republic of); Kim, Hye Jeong [Dept. of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul (Korea, Republic of)

    2016-09-15

    The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20 .deg. ) infusion group, and localized warm-saline (37 .deg. ) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min{sup -1} vs. 0.07 ± 0.02 min{sup -1},p = 0.661 for K{sup trans}; 0.30 ± 0.05 min{sup -1} vs. 0.37 ± 0.11 min{sup -1},p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Localized brain cooling (20 .deg. ) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37 .deg. ) infusion group.

  4. Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in Mice

    Directory of Open Access Journals (Sweden)

    Maiko Satomoto

    2016-01-01

    Full Text Available In rodents, neonatal sevoflurane exposure induces neonatal apoptosis in the brain and results in learning deficits. Sugammadex is a new selective neuromuscular blockade (NMB binding agent that anesthesiologists can use to achieve immediate reversal of an NMB with few side effects. Given its molecular weight of 2178, sugammadex is thought to be unable to pass through the blood brain barrier (BBB. Volatile anesthetics can influence BBB opening and integrity. Therefore, we investigated whether the intraperitoneal administration of sugammadex could exacerbate neuronal damage following neonatal 2% sevoflurane exposure via changes in BBB integrity. Cleaved caspase-3 immunoblotting was used to detect apoptosis, and the ultrastructure of the BBB was examined by transmission electron microscopy. Exposure to 2% sevoflurane for 6 h resulted in BBB ultrastructural abnormalities in the hippocampus of neonatal mice. Sugammadex alone without sevoflurane did not induce apoptosis. The coadministration of sugammadex with sevoflurane to neonatal mice caused a significant increase (150% in neuroapoptosis in the brain compared with 2% sevoflurane. In neonatal anesthesia, sugammadex could influence neurotoxicity together with sevoflurane. Exposure to 2% sevoflurane for 6 h resulted in BBB ultrastructural abnormalities in the hippocampus of neonatal mice.

  5. Improved survival in rats with glioma using MRI-guided focused ultrasound and microbubbles to disrupt the blood-brain barrier and deliver Doxil

    Science.gov (United States)

    Aryal, Muna; Zhi Zhang, Yong; Vykhodtseva, Natalia; Park, Juyoung; Power, Chanikarn; McDannold, Nathan

    2012-02-01

    Blood-brain-barrier (BBB) limits the transportation of most neuropeptides, proteins (enzymes, antibodies), chemotherapeutic agents, and genes that have therapeutic potential for the treatment of brain diseases. Different methods have been used to overcome this limitation, but they are invasive, non-targeted, or require the development of new drugs. We have developed a method that uses MRI-guided focused ultrasound (FUS) combined with circulating microbubbles to temporarily open BBB in and around brain tumors to deliver chemotherapy agents. Here, we tested whether this noninvasive technique could enhance the effectiveness of a chemotherapy agent (Doxil). Using 690 kHz FUS transducer and microbubble (Definity), we induced BBB disruption in intracranially-implanted 9L glioma tumors in rat's brain in three weekly sessions. Animals who received BBB disruption and Doxil had a median survival time of 34.5 days, which was significantly longer than that found in control animals which is 16, 18.5, 21 days who received no treatment, BBB disruption only and Doxil only respectively This work demonstrates that FUS technique has promise in overcoming barriers to drug delivery, which are particularly stark in the brain due to the BBB.

  6. Steroid Transport, Local Synthesis, and Signaling within the Brain: Roles in Neurogenesis, Neuroprotection, and Sexual Behaviors

    Directory of Open Access Journals (Sweden)

    Nicolas Diotel

    2018-02-01

    Full Text Available Sex steroid hormones are synthesized from cholesterol and exert pleiotropic effects notably in the central nervous system. Pioneering studies from Baulieu and colleagues have suggested that steroids are also locally-synthesized in the brain. Such steroids, called neurosteroids, can rapidly modulate neuronal excitability and functions, brain plasticity, and behavior. Accumulating data obtained on a wide variety of species demonstrate that neurosteroidogenesis is an evolutionary conserved feature across fish, birds, and mammals. In this review, we will first document neurosteroidogenesis and steroid signaling for estrogens, progestagens, and androgens in the brain of teleost fish, birds, and mammals. We will next consider the effects of sex steroids in homeostatic and regenerative neurogenesis, in neuroprotection, and in sexual behaviors. In a last part, we will discuss the transport of steroids and lipoproteins from the periphery within the brain (and vice-versa and document their effects on the blood-brain barrier (BBB permeability and on neuroprotection. We will emphasize the potential interaction between lipoproteins and sex steroids, addressing the beneficial effects of steroids and lipoproteins, particularly HDL-cholesterol, against the breakdown of the BBB reported to occur during brain ischemic stroke. We will consequently highlight the potential anti-inflammatory, anti-oxidant, and neuroprotective properties of sex steroid and lipoproteins, these latest improving cholesterol and steroid ester transport within the brain after insults.

  7. Hypoxic Stress and Inflammatory Pain Disrupt Blood-Brain Barrier Tight Junctions: Implications for Drug Delivery to the Central Nervous System.

    Science.gov (United States)

    Lochhead, Jeffrey J; Ronaldson, Patrick T; Davis, Thomas P

    2017-07-01

    A functional blood-brain barrier (BBB) is necessary to maintain central nervous system (CNS) homeostasis. Many diseases affecting the CNS, however, alter the functional integrity of the BBB. It has been shown that various diseases and physiological stressors can impact the BBB's ability to selectively restrict passage of substances from the blood to the brain. Modifications of the BBB's permeability properties can potentially contribute to the pathophysiology of CNS diseases and result in altered brain delivery of therapeutic agents. Hypoxia and/or inflammation are central components of a number of diseases affecting the CNS. A number of studies indicate hypoxia or inflammatory pain increase BBB paracellular permeability, induce changes in the expression and/or localization of tight junction proteins, and affect CNS drug uptake. In this review, we look at what is currently known with regard to BBB disruption following a hypoxic or inflammatory insult in vivo. Potential mechanisms involved in altering tight junction components at the BBB are also discussed. A more detailed understanding of the mediators involved in changing BBB functional integrity in response to hypoxia or inflammatory pain could potentially lead to new treatments for CNS diseases with hypoxic or inflammatory components. Additionally, greater insight into the mechanisms involved in TJ rearrangement at the BBB may lead to novel strategies to pharmacologically increase delivery of drugs to the CNS.

  8. Opening of the blood-brain barrier before cerebral pathology in mild hyperhomocysteinemia.

    Directory of Open Access Journals (Sweden)

    Bryce C Rhodehouse

    Full Text Available Hyperhomocysteinemia (HHcy is a risk factor for cognitive impairment. The purpose of this study was to determine the temporal pattern of cerebral pathology in a mouse model of mild HHcy, because understanding this time course provides the basis for understanding the mechanisms involved. C57Bl/6 mice with heterozygous deletion cystathionine β-synthase (cbs (+/-; Het were used as a model of mild HHcy along with their wild-type littermates (cbs (+/+; WT. Mice were 'young' (5.3±0.2 months of age and 'old' (16.6±0.9 months of age. Blood-brain barrier (BBB permeability was quantified from Evans blue and sodium fluorescein extravasation. Microvascular architecture was assessed by z-stack confocal microscopy. Leukoaraiosis was measured from Luxol fast blue stained slides of paraffin brain sections. Inflammation was quantified using standard antibody-based immunohistochemical techniques. Cognitive function was assessed using the Morris water maze. BBB permeability was significantly greater in Het vs. WT mice at all ages (p<0.05. There were no differences in microvascular architecture among the groups. Compared with all other groups, old Het mice had significantly greater leukoaraiosis, inflammation in the fornix, and cognitive impairment (p<0.05. In mild HHcy, increased permeability of the BBB precedes the onset of cerebral pathology. This new paradigm may play a role in the progression of disease in HHcy.

  9. Zinc ions regulate opening of tight junction favouring efflux of macromolecules via the GSK3β/snail-mediated pathway.

    Science.gov (United States)

    Xiao, Ruyue; Yuan, Lan; He, Weijiang; Yang, Xiaoda

    2018-01-24

    Zinc is an essential trace element presenting in particularly high concentration in the brain. In some regions, e.g. lateral amygdala, subiculum and hippocampus, rapidly-exchangeable zinc may transiently reach even up to 600 μM. To explore the possible roles of high-concentration Zn 2+ in regulating the blood-brain barrier (BBB), we investigated the effects of Zn 2+ on the functions and structures of the tight junction (TJ) with an in vitro model of a Madin-Darby canine kidney (MDCK) cell monolayer. The experimental results indicated that high concentrations (>200 μM) of Zn 2+ can affect the TJ integrity in a polarized manner. Basolateral addition of Zn 2+ led to reversible TJ opening with pore paths of r ∼ 2 nm or more depending on Zn 2+ concentration. The efflux/influx ratios of different sized probes were found to be ∼4.6 for FD4 (M W 4000) and ∼1.8 for Eu-DTPA (M W 560), suggesting that the Zn 2+ -induced paracelluar channels favour efflux especially for macromolecules. Further mechanistic studies revealed that the elevated intracellular Zn 2+ taken from the basolateral side can increase phosphorylation of glycogen synthase kinase (GSK) 3β, primarily due to the inhibition of calcineurin (CaN), thus resulting in the elevation of the snail transcriptional repressors. Subsequently, Zn 2+ can cause the down-regulation of claudin-1, breakage of occludin and ZO-1 rings, and collapse of basolateral F-actin structures. These overall factors result in the formation of a trumpet-like paracellular channel, which allows asymmetric solute permeation. The ERK1/2 and JNK1/2 pathways may also be involved in the Zn 2+ -induced TJ opening process, while the activation of matrix metalloproteinase was not observed. Our results may suggest a potential role of zinc in regulation of BBB permeability associated with brain clearance of metabolites through the glymphatic system.

  10. Maintenance of Blood-Brain Barrier Integrity in Hypertension: A Novel Benefit of Exercise Training for Autonomic Control

    Directory of Open Access Journals (Sweden)

    Leila Buttler

    2017-12-01

    Full Text Available The blood-brain barrier (BBB is a complex multicellular structure acting as selective barrier controlling the transport of substances between these compartments. Accumulating evidence has shown that chronic hypertension is accompanied by BBB dysfunction, deficient local perfusion and plasma angiotensin II (Ang II access into the parenchyma of brain areas related to autonomic circulatory control. Knowing that spontaneously hypertensive rats (SHR exhibit deficient autonomic control and brain Ang II hyperactivity and that exercise training is highly effective in correcting both, we hypothesized that training, by reducing Ang II content, could improve BBB function within autonomic brain areas of the SHR. After confirming the absence of BBB lesion in the pre-hypertensive SHR, but marked fluorescein isothiocyanate dextran (FITC, 10 kD leakage into the brain parenchyma of the hypothalamic paraventricular nucleus (PVN, nucleus of the solitary tract, and rostral ventrolateral medulla during the established phase of hypertension, adult SHR, and age-matched WKY were submitted to a treadmill training (T or kept sedentary (S for 8 weeks. The robust FITC leakage within autonomic areas of the SHR-S was largely reduced and almost normalized since the 2nd week of training (T2. BBB leakage reduction occurred simultaneously and showed strong correlations with both decreased LF/HF ratio to the heart and reduced vasomotor sympathetic activity (power spectral analysis, these effects preceding the appearance of resting bradycardia (T4 and partial pressure fall (T8. In other groups of SHR-T simultaneously infused with icv Ang II or saline (osmotic mini-pumps connected to a lateral ventricle cannula we proved that decreased local availability of this peptide and reduced microglia activation (IBA1 staining are crucial mechanisms conditioning the restoration of BBB integrity. Our data also revealed that Ang II-induced BBB lesion was faster within the PVN (T2, suggesting

  11. openBIS ELN-LIMS: an open-source database for academic laboratories.

    Science.gov (United States)

    Barillari, Caterina; Ottoz, Diana S M; Fuentes-Serna, Juan Mariano; Ramakrishnan, Chandrasekhar; Rinn, Bernd; Rudolf, Fabian

    2016-02-15

    The open-source platform openBIS (open Biology Information System) offers an Electronic Laboratory Notebook and a Laboratory Information Management System (ELN-LIMS) solution suitable for the academic life science laboratories. openBIS ELN-LIMS allows researchers to efficiently document their work, to describe materials and methods and to collect raw and analyzed data. The system comes with a user-friendly web interface where data can be added, edited, browsed and searched. The openBIS software, a user guide and a demo instance are available at https://openbis-eln-lims.ethz.ch. The demo instance contains some data from our laboratory as an example to demonstrate the possibilities of the ELN-LIMS (Ottoz et al., 2014). For rapid local testing, a VirtualBox image of the ELN-LIMS is also available. © The Author 2015. Published by Oxford University Press.

  12. The application of MRI for depiction of subtle blood brain barrier disruption in stroke.

    Science.gov (United States)

    Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

    2010-12-26

    The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in

  13. Exceptional groups from open strings

    International Nuclear Information System (INIS)

    Gaberdiel, M.R.; Zwiebach, B.

    1998-01-01

    We consider type IIB theory compactified on a two-sphere in the presence of mutually non-local 7-branes. The BPS states associated with the gauge vectors of exceptional groups are seen to arise from open strings connecting the 7-branes, and multi-pronged open strings capable of ending on more than two 7-branes. These multi-pronged strings are built from open string junctions that arise naturally when strings cross 7-branes. The different string configurations can be multiplied as traditional open strings, and are shown to generate the structure of exceptional groups. (orig.)

  14. Hölder and locally Hölder continuous functions, and open sets of class C^k, C^{k,lambda}

    CERN Document Server

    Fiorenza, Renato

    2016-01-01

    This book offers a systematic treatment of a classic topic in Analysis. It fills a gap in the existing literature by presenting in detail the classic λ-Hölder condition and introducing the notion of locally Hölder-continuous function in an open set Ω in Rn. Further, it provides the essential notions of multidimensional geometry applied to analysis. Written in an accessible style and with proofs given as clearly as possible, it is a valuable resource for graduate students in Mathematical Analysis and researchers dealing with Hölder-continuous functions and their applications.

  15. A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model

    OpenAIRE

    Sara Neves-Coelho; Rute P. Eleutério; Francisco J. Enguita; Vera Neves; Miguel A. R. B. Castanho

    2017-01-01

    © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). The capacity to transport therapeutic molecules across the blood–brain barrier (BBB) represents a breakthrough in the development of tools for the treatment of many central nervous system (CNS)-associated diseases. The BBB, while being protective against ...

  16. Drug and xenobiotic biotransformation in the blood-brain barrier: A neglected issue.

    Directory of Open Access Journals (Sweden)

    José A.G. Agúndez

    2014-10-01

    Full Text Available Drug biotransformation is a crucial mechanism for facilitating the elimination of chemicals from the organism and for decreasing their pharmacological activity. Published evidence suggests that brain drug metabolism may play a role in the development of adverse drug reactions and in the clinical response to drugs and xenobiotics. The blood-brain barrier (BBB has been regarded mainly as a physical barrier for drugs and xenobiotics, and little attention has been paid to BBB as a drug-metabolizing barrier. The presence of drug metabolizing enzymes in the BBB is likely to have functional implications because local metabolism may inactivate drugs or may modify the drug's ability to cross the BBB, thus modifying the drug response and the risk of developing adverse drug reactions. In this perspective paper, we discuss the expression of relevant xenobiotic metabolizing enzymes in the brain and in the BBB, and we cover current advances and future directions on the potential role of these BBB drug-metabolizing enzymes as modifiers of drug response.

  17. Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior.

    Science.gov (United States)

    Hindle, Samantha J; Munji, Roeben N; Dolghih, Elena; Gaskins, Garrett; Orng, Souvinh; Ishimoto, Hiroshi; Soung, Allison; DeSalvo, Michael; Kitamoto, Toshihiro; Keiser, Michael J; Jacobson, Matthew P; Daneman, Richard; Bainton, Roland J

    2017-10-31

    Central nervous system (CNS) chemical protection depends upon discrete control of small-molecule access by the blood-brain barrier (BBB). Curiously, some drugs cause CNS side-effects despite negligible transit past the BBB. To investigate this phenomenon, we asked whether the highly BBB-enriched drug efflux transporter MDR1 has dual functions in controlling drug and endogenous molecule CNS homeostasis. If this is true, then brain-impermeable drugs could induce behavioral changes by affecting brain levels of endogenous molecules. Using computational, genetic, and pharmacologic approaches across diverse organisms, we demonstrate that BBB-localized efflux transporters are critical for regulating brain levels of endogenous steroids and steroid-regulated behaviors (sleep in Drosophila and anxiety in mice). Furthermore, we show that MDR1-interacting drugs are associated with anxiety-related behaviors in humans. We propose a general mechanism for common behavioral side effects of prescription drugs: pharmacologically challenging BBB efflux transporters disrupts brain levels of endogenous substrates and implicates the BBB in behavioral regulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Barrier mechanisms in the Drosophila blood-brain barrier.

    Science.gov (United States)

    Hindle, Samantha J; Bainton, Roland J

    2014-01-01

    The invertebrate blood-brain barrier (BBB) field is growing at a rapid pace and, in recent years, studies have shown a physiologic and molecular complexity that has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular barrier maintenance through G-protein coupled receptor signaling were the first demonstrations of the complex adaptive mechanisms of barrier physiology. Building upon this work, the integrity of the invertebrate BBB has recently been shown to require coordinated function of all layers of the compound barrier structure, analogous to signaling between the layers of the vertebrate neurovascular unit. These findings strengthen the notion that many BBB mechanisms are conserved between vertebrates and invertebrates, and suggest that novel findings in invertebrate model organisms will have a significant impact on the understanding of vertebrate BBB functions. In this vein, important roles in coordinating localized and systemic signaling to dictate organism development and growth are beginning to show how the BBB can govern whole animal physiologies. This includes novel functions of BBB gap junctions in orchestrating synchronized neuroblast proliferation, and of BBB secreted antagonists of insulin receptor signaling. These advancements and others are pushing the field forward in exciting new directions. In this review, we provide a synopsis of invertebrate BBB anatomy and physiology, with a focus on insights from the past 5 years, and highlight important areas for future study.

  19. Effective Drug Delivery in Diffuse Intrinsic Pontine Glioma: A Theoretical Model to Identify Potential Candidates

    Directory of Open Access Journals (Sweden)

    Fatma E. El-Khouly

    2017-10-01

    Full Text Available Despite decades of clinical trials for diffuse intrinsic pontine glioma (DIPG, patient survival does not exceed 10% at two years post-diagnosis. Lack of benefit from systemic chemotherapy may be attributed to an intact bloodbrain barrier (BBB. We aim to develop a theoretical model including relevant physicochemical properties in order to review whether applied chemotherapeutics are suitable for passive diffusion through an intact BBB or whether local administration via convection-enhanced delivery (CED may increase their therapeutic potential. Physicochemical properties (lipophilicity, molecular weight, and charge in physiological environment of anticancer drugs historically and currently administered to DIPG patients, that affect passive diffusion over the BBB, were included in the model. Subsequently, the likelihood of BBB passage of these drugs was ascertained, as well as their potential for intratumoral administration via CED. As only non-molecularly charged, lipophilic, and relatively small sized drugs are likely to passively diffuse through the BBB, out of 51 drugs modeled, only 8 (15%—carmustine, lomustine, erlotinib, vismodegib, lenalomide, thalidomide, vorinostat, and mebendazole—are theoretically qualified for systemic administration in DIPG. Local administration via CED might create more therapeutic options, excluding only positively charged drugs and drugs that are either prodrugs and/or only available as oral formulation. A wide variety of drugs have been administered systemically to DIPG patients. Our model shows that only few are likely to penetrate the BBB via passive diffusion, which may partly explain the lack of efficacy. Drug distribution via CED is less dependent on physicochemical properties and may increase the therapeutic options for DIPG.

  20. ADAPTING OPEN-SOURCE SOFTWARE FOR ENTERPRISE

    Directory of Open Access Journals (Sweden)

    Bogdan MICU GHILIC

    2013-06-01

    Full Text Available Low developed companies do not use ERP solutions for resource management, they don't have CRM systems for tracking customers, online presence is low and consequently they are selling low volumes. Their work does not generate enough capital to buy specialized software and the local community is too small to create open-source software for them.When adapting an open-source enterprise solution, from a certain level of integration, it is necessary to align to the Romanian legislation. For this you need more than a simple translation. For example, in accounting, the Romanian chart of accounts should be used, the local fiscal calendar, the rules of the Romanian legislation and the specific identifiers for Romanian companies. The solution: Open source applications can be localized. A small community cannot create complex system starting from nothing, but they can adapt existing ones already created and used all over the world. Given the individual characteristics of the Romanian market, open source ERP, CM and e-commerce will be integrated by specialized consultancy agency in Romania just as is done in France (Compiere, Spain (Openbravo, Belgium (OpenERP or the United States (Apache oFBiz. This will not generate license costs for the companies, only the expenses for hardware and implementation consultancy. If we can create a common infrastructure, hardware cost will be waived for cloud SaaS offering, in opposition with the on-premise option.

  1. openBEB: open biological experiment browser for correlative measurements.

    Science.gov (United States)

    Ramakrishnan, Chandrasekhar; Bieri, Andrej; Sauter, Nora; Roizard, Sophie; Ringler, Philippe; Müller, Shirley A; Goldie, Kenneth N; Enimanev, Kaloyan; Stahlberg, Henning; Rinn, Bernd; Braun, Thomas

    2014-03-26

    New experimental methods must be developed to study interaction networks in systems biology. To reduce biological noise, individual subjects, such as single cells, should be analyzed using high throughput approaches. The measurement of several correlative physical properties would further improve data consistency. Accordingly, a considerable quantity of data must be acquired, correlated, catalogued and stored in a database for subsequent analysis. We have developed openBEB (open Biological Experiment Browser), a software framework for data acquisition, coordination, annotation and synchronization with database solutions such as openBIS. OpenBEB consists of two main parts: A core program and a plug-in manager. Whereas the data-type independent core of openBEB maintains a local container of raw-data and metadata and provides annotation and data management tools, all data-specific tasks are performed by plug-ins. The open architecture of openBEB enables the fast integration of plug-ins, e.g., for data acquisition or visualization. A macro-interpreter allows the automation and coordination of the different modules. An update and deployment mechanism keeps the core program, the plug-ins and the metadata definition files in sync with a central repository. The versatility, the simple deployment and update mechanism, and the scalability in terms of module integration offered by openBEB make this software interesting for a large scientific community. OpenBEB targets three types of researcher, ideally working closely together: (i) Engineers and scientists developing new methods and instruments, e.g., for systems-biology, (ii) scientists performing biological experiments, (iii) theoreticians and mathematicians analyzing data. The design of openBEB enables the rapid development of plug-ins, which will inherently benefit from the "house keeping" abilities of the core program. We report the use of openBEB to combine live cell microscopy, microfluidic control and visual

  2. Comparison of efficacy of spinal anaesthesia and sub-fascial local anaesthetic inguinal field block for open inguinal hernia repair-a single institutional experience

    International Nuclear Information System (INIS)

    Shafique, N.; Rashid, H.U.; Raja, M.I.; Saeed, M.

    2015-01-01

    The use of local anaesthetic for open inguinal hernia surgery has long been restricted to specialist centres. This study aimed to compare the efficacy of spinal anaesthesia and sub-fascial local anaesthetic (LA) for performing open hernia repair and at the same time provide better post op pain relief and early mobilization. Methods: In this randomized clinical trial, 62 male patients aged 16-72 were randomly allocated to two groups. Group A received mixture of 20ml 0.5% bupivacain, 20ml 2% lignocaine with adrenaline, 20ml normal saline (N/S), 3 ml NaHCO/sub 3/ sub-fascially for Local anaesthetic (LA) inguinal field block, while Group B received Spinal Anaesthesia (SA) with 0.5% Bupivacaine. Comparison was made in terms of Visual Analogue Score (VAS) recorded intra-operatively at 0 and 30 minutes and post operatively at 2, 4 and 12 hours at rest and on movement. Need for rescue analgesia and total analgesic consumption in both groups were calculated. Interval to pain free ambulation as well as procedural and anaesthesia related complications were compared. Results: Mean VAS in the intraoperative period were significantly high in Group A (p-value 0.011) at the start of operation and at 30 minutes (p-value <0.001). However, it did not correlate with patient satisfaction as 90% of patients in Group A successfully underwent the procedure without need for supplemental analgesia. VAS scores at rest and on movement/cough were comparable in the post op period at 2, 4 and 12 hours in both groups. Interval to pain free ambulation was significantly low in Group A (p-value 0.0012). Conclusion: Sub facial LA inguinal field block provides effective anaesthesia with optimum post op analgesia, prompt recovery and fewer systemic side effects compared to SA and can safely be used for routine open inguinal hernia surgery. (author)

  3. Enhanced tumor cell killing following BNCT with hyperosmotic mannitol-induced blood-brain barrier disruption and intracarotid injection of boronophenylalanine

    International Nuclear Information System (INIS)

    Hsieh, C.H.; Hwang, J.J.; Chen, F.D.; Liu, R.S.; Liu, H.M.; Hsueh, Y.W.; Kai, J.J.

    2006-01-01

    The delivery of boronophenylalanine (BPA) by means of intracarotid injection combined with opening the blood-brain barrier (BBB) have been shown significantly enhanced the tumor boron concentration and the survival time of glioma-bearing rats. However, no direct evidence demonstrates whether this treatment protocol can enhance the cell killing of tumor cells or infiltrating tumor cells and the magnitude of enhanced cell killing. The purpose of the present study was to determine if the tumor cell killing of boron neutron capture therapy could be enhanced by hyperosmotic mannitol-induced BBB disruption using BPA-Fr as the capture agent. F98 glioma-bearing rats were injected intravenously or intracarotidly with BPA at doses of 500 mg/kg body weight (b.w.) and with or without mannitol-induced hyperosmotic BBB disruption. The rats were irradiated with an epithermal neutron beam at the reactor of National Tsing-Hua University (THOR). After neutron beam irradiation, the rats were euthanized and the ipsilateral brains containing intracerebral F98 glioma were removed to perform in vivo/in vitro soft agar clonogenic assay. The results demonstrate BNCT with optimizing the delivery of BPA by means of intracarotid injection combined with opening the BBB by infusing a hyperosmotic solution of mannitol significantly enhanced the cell killing of tumor cells and infiltrating tumor cells, the tumor boron concentration and the boron ratio of tumor to normal brain tissues. (author)

  4. Structure feuilletée de l'espace de Kuranishi et isomorphismes de familles de déformations de variétés compactes complexes

    OpenAIRE

    Meersseman , Laurent

    2011-01-01

    International audience; Consider the following uniformization problem. Take two holomorphic (parametrized by some analytic set defined on a neighborhood of $0$ in $\\Bbb C^p$, for some $p>0$) or differentiable (parametrized by an open neighborhood of $0$ in $\\Bbb R^p$, for some $p>0$) deformation families of compact complex manifolds. Assume they are pointwise isomorphic, that is for each point $t$ of the parameter space, the fiber over $t$ of the first family is biholomorphic to the fiber ove...

  5. Blood–brain barrier and laser technology for drug brain delivery

    Directory of Open Access Journals (Sweden)

    Oxana V. Semyachkina-Glushkovskaya

    2017-09-01

    Photodynamic therapy (PDT is usual clinical method of surgical navigation for the resection of brain tumor and anti-cancer therapy. Nowadays, the application of PDT is considered as a potential promising tool for brain drug delivery via opening of BBB. Here, we show the first successful experimental results in this field discussing the adventures and disadvantages of PDT-related BBB disruption as well as alternatives to overcome these limitations and possible mechanisms with new pathways for brain clearance via glymphatic and lymphatic systems.

  6. OpenBAN: An Open Building ANalytics Middleware for Smart Buildings

    Directory of Open Access Journals (Sweden)

    Pandarasamy Arjunan

    2016-03-01

    Full Text Available Towards the realization of smart building applications, buildings are increasingly instrumented with diverse sensors and actuators. These sensors generate large volumes of data which can be analyzed for optimizing building operations. Many building energy management tasks such as energy forecasting, disaggregation, among others require complex analytics leveraging collected sensor data. While several standalone and cloud-based systems for archiving, sharing and visualizing sensor data have emerged, their support for analyzing sensor data streams is primitive and limited to rule-based actions based on thresholds and simple aggregation functions. We develop OpenBAN, an open source sensor data analytics middleware for buildings, to make analytics an integral component of modern smart building applications. OpenBAN provides a framework of extensible sensor data processing elements for identifying various building context, which different applications can leverage. We validate the capabilities of OpenBAN by developing three representative real-world applications which are deployed in our test-bed buildings: (i household energy disaggregation, (ii detection of sprinkler usage from water meter data, and (iii electricity demand forecasting. We also provide a preliminary system performance of OpenBAN when deployed in the cloud and locally.

  7. Outcome of patients undergoing open heart surgery at the Uganda ...

    African Journals Online (AJOL)

    An approach in which open heart surgeries are conducted locally by visiting teams enabling skills transfer to the local team and helps build to build capacity has been adopted at the Uganda Heart Institute (UHI). Objectives: We reviewed the progress of open heart surgery at the UHI and evaluated the postoperative ...

  8. Quasi-open inflation

    CERN Document Server

    García-Bellido, J; Montes, X; Garcia-Bellido, Juan; Garriga, Jaume; Montes, Xavier

    1998-01-01

    We show that a large class of two-field models of single-bubble open inflation do not lead to infinite open universes, as it was previously thought, but to an ensemble of very large but finite inflating `islands'. The reason is that the quantum tunneling responsible for the nucleation of the bubble does not occur simultaneously along both field directions and equal-time hypersurfaces in the open universe are not synchronized with equal-density or fixed-field hypersurfaces. The most probable tunneling trajectory corresponds to a zero value of the inflaton field; large values, necessary for the second period of inflation inside the bubble, only arise as localized fluctuations. The interior of each nucleated bubble will contain an infinite number of such inflating regions of comoving size of order $\\gamma^{-1}$, where $\\gamma$ depends on the parameters of the model. Each one of these islands will be a quasi-open universe. Since the volume of the hyperboloid is infinite, inflating islands with all possible values...

  9. Neurotoxicity after intracarotid 1,3-bis(2-chloroethyl)-1-nitrosourea administration in the rat: Hemodynamic changes studied by double-tracer autoradiography

    International Nuclear Information System (INIS)

    Nagahiro, S.; Yamamoto, Y.L.; Diksic, M.; Mitsuka, S.; Sugimoto, S.; Feindel, W.

    1991-01-01

    Changes in blood-brain (BBB) permeability and local cerebral blood flow after intracarotid administration of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were examined quantitatively in rats with double-tracer autoradiography using [14C]alpha-amino-isobutyric acid and [18F]fluoroantipyrine. Forty-eight female Wistar rats were divided into four groups. The control group (Group 1) received 1 ml of 5% dextrose. The other three groups received three different doses of BCNU dissolved in 5% dextrose: Group 2 rats received 1 mg, Group 3 3 mg, and Group 4 10 mg. The tracer study was performed on Day 1 or Days 4 to 12 after intracarotid administration of BCNU. In 11 rats in Group 2, there were no changes of BBB permeability. Transient BBB permeability changes were seen in the striatum or hippocampus in 3 of the 5 rats (60%) in Group 3 within 24 hours. In 8 of 9 rats (89%) in the same group, late BBB permeability changes were observed in the hypothalamus with or without histological changes. BBB permeability changes were seen in all rats of Group 4. Focal increase of local cerebral blood flow on the infused side compared with the non-infused side of the brain was observed, although not at a significant level, in 5 of 25 rats examined with [18F]fluoroantipyrine. The results of BBB permeability and histological examinations and study of heterogenous distribution by [18F]fluorodeoxyglucose indicated that the ipsilateral subcortical structures such as the hypothalamus, amygdala, internal capsule, and caudate putamen have the highest incidence of neurotoxicity, which are closely related to histopathological damage seen in human BCNU leucoencephalopathy

  10. The thermodynamic meaning of local temperature of nonequilibrium open quantum systems

    OpenAIRE

    Ye, LvZhou; Zheng, Xiao; Yan, YiJing; Di Ventra, Massimiliano

    2016-01-01

    Measuring the local temperature of nanoscale systems out of equilibrium has emerged as a new tool to study local heating effects and other local thermal properties of systems driven by external fields. Although various experimental protocols and theoretical definitions have been proposed to determine the local temperature, the thermodynamic meaning of the measured or defined quantities remains unclear. By performing analytical and numerical analysis of bias-driven quantum dot systems both in ...

  11. Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system

    Science.gov (United States)

    Aryal, Muna; Arvanitis, Costas D.; Alexander, Phillip M.; McDannold, Nathan

    2014-01-01

    The physiology of the vasculature in the central nervous system (CNS), which includes the blood-brain barrier (BBB) and other factors, complicates the delivery of most drugs to the brain. Different methods have been used to bypass the BBB, but they have limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Focused ultrasound (FUS), when combined with circulating microbubbles, is a noninvasive method to locally and transiently disrupt the BBB at discrete targets. This review provides insight on the current status of this unique drug delivery technique, experience in preclinical models, and potential for clinical translation. If translated to humans, this method would offer a flexible means to target therapeutics to desired points or volumes in the brain, and enable the whole arsenal of drugs in the CNS that are currently prevented by the BBB. PMID:24462453

  12. Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

    Directory of Open Access Journals (Sweden)

    Umberto Tosi

    2017-02-01

    Full Text Available Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

  13. Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

    Science.gov (United States)

    Tosi, Umberto; Marnell, Christopher S.; Chang, Raymond; Cho, William C.; Ting, Richard; Maachani, Uday B.; Souweidane, Mark M.

    2017-01-01

    Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents. PMID:28208698

  14. Foliated Structure of The Kuranishi Space and Isomorphisms of Deformation Families of Compact Complex Manifolds

    OpenAIRE

    Meersseman, Laurent

    2009-01-01

    Consider the following uniformization problem. Take two holomorphic (parametrized by some analytic set defined on a neighborhood of $0$ in $\\Bbb C^p$, for some $p>0$) or differentiable (parametrized by an open neighborhood of $0$ in $\\Bbb R^p$, for some $p>0$) deformation families of compact complex manifolds. Assume they are pointwise isomorphic, that is for each point $t$ of the parameter space, the fiber over $t$ of the first family is biholomorphic to the fiber over $t$ of the second fami...

  15. Design of Local Ventilation by Full-Scale and Scale Modelling Techniques

    DEFF Research Database (Denmark)

    Nielsen, Peter V.

    This paper will show the experiments with local ventilation of a filling machine from the paint industry, local ventilation of a film developing machine, experiments with a vortex exhaust opening and local heating of a checkout assistant's working place.......This paper will show the experiments with local ventilation of a filling machine from the paint industry, local ventilation of a film developing machine, experiments with a vortex exhaust opening and local heating of a checkout assistant's working place....

  16. A feminist approach to open government: investing in gender ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    A feminist approach to open government: investing in gender equality to drive sustainable ... Current open government practices limit the ability of women and other ... accessing government information at the local level as compared to men.

  17. Open source GIS for HIV/AIDS management

    Directory of Open Access Journals (Sweden)

    Ricketts Adam

    2008-10-01

    Full Text Available Abstract Background Reliable access to basic services can improve a community's resilience to HIV/AIDS. Accordingly, work is being done to upgrade the physical infrastructure in affected areas, often employing a strategy of decentralised service provision. Spatial characteristics are one of the major determinants in implementing services, even in the smaller municipal areas, and good quality spatial information is needed to inform decision making processes. However, limited funds, technical infrastructure and human resource capacity result in little or no access to spatial information for crucial infrastructure development decisions at local level. This research investigated whether it would be possible to develop a GIS for basic infrastructure planning and management at local level. Given the resource constraints of the local government context, particularly in small municipalities, it was decided that open source software should be used for the prototype system. Results The design and development of a prototype system illustrated that it is possible to develop an open source GIS system that can be used within the context of local information management. Usability tests show a high degree of usability for the system, which is important considering the heavy workload and high staff turnover that characterises local government in South Africa. Local infrastructure management stakeholders interviewed in a case study of a South African municipality see the potential for the use of GIS as a communication tool and are generally positive about the use of GIS for these purposes. They note security issues that may arise through the sharing of information, lack of skills and resource constraints as the major barriers to adoption. Conclusion The case study shows that spatial information is an identified need at local level. Open source GIS software can be used to develop a system to provide local-level stakeholders with spatial information. However, the

  18. LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-β.

    Science.gov (United States)

    Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

    2012-11-14

    Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer's disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in cerebrovasculature, in particular in vascular smooth muscle cells. Previous studies have indicated a role of LRP1 in endothelial cells in transcytosing Aβ out of the brain across the BBB; however, whether this represents a significant pathway for brain Aβ clearance remains controversial. Here, we demonstrate that Aβ can be cleared locally in the cerebrovasculature by an LRP1-dependent endocytic pathway in smooth muscle cells. The uptake and degradation of both endogenous and exogenous Aβ were significantly reduced in LRP1-suppressed human brain vascular smooth muscle cells. Conditional deletion of Lrp1 in vascular smooth muscle cell in amyloid model APP/PS1 mice accelerated brain Aβ accumulation and exacerbated Aβ deposition as amyloid plaques and CAA without affecting Aβ production. Our results demonstrate that LRP1 is a major Aβ clearance receptor in cerebral vascular smooth muscle cell and a disturbance of this pathway contributes to Aβ accumulation. These studies establish critical functions of the cerebrovasculature system in Aβ metabolism and identify a new pathway involved in the pathogenesis of both AD and CAA.

  19. Open space preservation, property value, and optimal spatial configuration

    Science.gov (United States)

    Yong Jiang; Stephen K. Swallow

    2007-01-01

    The public has increasingly demonstrated a strong support for open space preservation. How to finance the socially efficient level of open space with the optimal spatial structure is of high policy relevance to local governments. In this study, we developed a spatially explicit open space model to help identify the socially optimal amount and optimal spatial...

  20. Blood-Brain Barrier Disruption After Cardiopulmonary Bypass: Diagnosis and Correlation to Cognition.

    Science.gov (United States)

    Abrahamov, Dan; Levran, Oren; Naparstek, Sharon; Refaeli, Yael; Kaptson, Shani; Abu Salah, Mahmud; Ishai, Yaron; Sahar, Gideon

    2017-07-01

    Cardiopulmonary bypass (CPB) elicits a systemic inflammatory response that may impair blood-brain barrier (BBB) integrity. BBB disruption can currently be detected by dynamic contrast enhancement magnetic resonance imaging (MRI), reflected by an increase in the permeability constant (K trans ). We aimed to determine (1) whether CPB induces BBB disruption, (2) duration until BBB disruption resolution, and (3) the obtainable correlation between BBB injury (location and intensity) and neurocognitive dysfunction. Seven patients undergoing CPB with coronary artery bypass grafting (CABG) were assigned to serial cerebral designated MRI evaluations, preoperatively and on postoperative day (POD) 1 and 5. Examinations were analyzed for BBB disruption and microemboli using dynamic contrast enhancement MRI and diffusion-weighted imaging methods, respectively. Neuropsychologic tests were performed 1 day preoperatively and on POD 5. A significant local K trans increase (0.03 min -1 vs 0.07 min -1 , p = 0.033) compatible with BBB disruption was evident in 5 patients (71%) on POD 1. Resolution was observed by POD 5 (mean, 0.012 min -1 ). The location of the disruption was most prominent in the frontal lobes (400% vs 150% K trans levels upsurge, p = 0.05). MRI evidence of microembolization was demonstrated in only 1 patient (14%). The postoperative global cognitive score was reduced in all patients (98.2 ± 12 vs 95.1 ± 11, p = 0.032), predominantly in executive and attention (frontal lobe-related) functions (91.8 ± 13 vs 86.9 ± 12, p = 0.042). The intensity of the dynamic contrast enhancement MRI BBB impairment correlated with the magnitude of cognition reduction (r = 0.69, p = 0.04). BBB disruption was evident in most patients, primarily in the frontal lobes. The location and intensity of the BBB disruption, rather than the microembolic load, correlated with postoperative neurocognitive dysfunction. Copyright © 2017 The Society of Thoracic Surgeons. Published by

  1. ScienceSoft: Open software for open science

    CERN Document Server

    Di Meglio, Alberto

    2012-01-01

    Most of the software developed today by research institutes, university, research projects, etc. is typically stored in local source and binary repositories and available for the duration of a project lifetime only. Finding software based on given functional characteristics is almost impossible and binary packages are mostly available from local university or project repositories rather than the open source community repositories like Fedora/EPEL or Debian. Furthermore general information about who develops, contributes to and most importantly uses a given software program is very difficult to find out and yet the widespread availability of such information would give more visibility and credibility to the software products. The creation of links or relationships not only among pieces of software, but equally among the people interacting with the software across and beyond specific project and communities would foster a more active community and create the conditions for sharing ideas and skills, a ...

  2. On Bitopological Supra B-Open Sets

    OpenAIRE

    M.Lellis Thivagar; B.Meera Devi

    2012-01-01

    In this paper, we introduce and investigate a new class of sets and maps be- tween bitopological spaces called supra(1,2) b-open, and supra (1,2) b-continuous maps, respectively. Furthermore, we introduce the concepts of supra(1,2) locally-closed, supra(1,2) locally b-closed sets. We also introduce supra(1,2) extremely disconnected. Finally, additional properties of these sets are investigated.

  3. IRSN review 2011/2014. Openness to society - Review of actions, 5 years after the chart

    International Nuclear Information System (INIS)

    2015-01-01

    After having recalled the commitments defined by the Charter for Openness to Society adopted by the IRSN in 2009, this report proposes a review of undertaken and performed actions in terms of access to information, of openness to partnership (notably with local information commissions or CLIs, and also with other local actors), of influence of the openness on the Institute work orientation, and of internal culture of openness

  4. Open source system OpenVPN in a function of Virtual Private Network

    Science.gov (United States)

    Skendzic, A.; Kovacic, B.

    2017-05-01

    Using of Virtual Private Networks (VPN) can establish high security level in network communication. VPN technology enables high security networking using distributed or public network infrastructure. VPN uses different security and managing rules inside networks. It can be set up using different communication channels like Internet or separate ISP communication infrastructure. VPN private network makes security communication channel over public network between two endpoints (computers). OpenVPN is an open source software product under GNU General Public License (GPL) that can be used to establish VPN communication between two computers inside business local network over public communication infrastructure. It uses special security protocols and 256-bit Encryption and it is capable of traversing network address translators (NATs) and firewalls. It allows computers to authenticate each other using a pre-shared secret key, certificates or username and password. This work gives review of VPN technology with a special accent on OpenVPN. This paper will also give comparison and financial benefits of using open source VPN software in business environment.

  5. Sorting Tubules Regulate Blood-Brain Barrier Transcytosis

    Directory of Open Access Journals (Sweden)

    Roberto Villaseñor

    2017-12-01

    Full Text Available Transcytosis across the blood-brain barrier (BBB regulates key processes of the brain, but the intracellular sorting mechanisms that determine successful receptor-mediated transcytosis in brain endothelial cells (BECs remain unidentified. Here, we used Transferrin receptor-based Brain Shuttle constructs to investigate intracellular transport in BECs, and we uncovered a pathway for the regulation of receptor-mediated transcytosis. By combining live-cell imaging and mathematical modeling in vitro with super-resolution microscopy of the BBB, we show that intracellular tubules promote transcytosis across the BBB. A monovalent construct (sFab sorted for transcytosis was localized to intracellular tubules, whereas a bivalent construct (dFab sorted for degradation formed clusters with impaired transport along tubules. Manipulating tubule biogenesis by overexpressing the small GTPase Rab17 increased dFab transport into tubules and induced its transcytosis in BECs. We propose that sorting tubules regulate transcytosis in BECs and may be a general mechanism for receptor-mediated transport across the BBB.

  6. A choline derivate-modified nanoprobe for glioma diagnosis using MRI

    Science.gov (United States)

    Li, Jianfeng; Huang, Shixian; Shao, Kun; Liu, Yang; An, Sai; Kuang, Yuyang; Guo, Yubo; Ma, Haojun; Wang, Xuxia; Jiang, Chen

    2013-04-01

    Gadolinium (Gd) chelate contrast-enhanced magnetic resonance imaging (MRI) is a preferred method of glioma detection and preoperative localisation because it offers high spatial resolution and non-invasive deep tissue penetration. Gd-based contrast agents, such as Gd-diethyltriaminepentaacetic acid (DTPA-Gd, Magnevist), are widely used clinically for tumor diagnosis. However, the Gd-based MRI approach is limited for patients with glioma who have an uncompromised blood-brain barrier (BBB). Moreover, the rapid renal clearance and non-specificity of such contrast agents further hinders their prevalence. We present a choline derivate (CD)-modified nanoprobe with BBB permeability, glioma specificity and a long blood half-life. Specific accumulation of the nanoprobe in gliomas and subsequent MRI contrast enhancement are demonstrated in vitro in U87 MG cells and in vivo in a xenograft nude model. BBB and glioma dual targeting by this nanoprobe may facilitate precise detection of gliomas with an uncompromised BBB and may offer better preoperative and intraoperative tumor localization.

  7. HARVESTING, INTEGRATING AND DISTRIBUTING LARGE OPEN GEOSPATIAL DATASETS USING FREE AND OPEN-SOURCE SOFTWARE

    Directory of Open Access Journals (Sweden)

    R. Oliveira

    2016-06-01

    Full Text Available Federal, State and Local government agencies in the USA are investing heavily on the dissemination of Open Data sets produced by each of them. The main driver behind this thrust is to increase agencies’ transparency and accountability, as well as to improve citizens’ awareness. However, not all Open Data sets are easy to access and integrate with other Open Data sets available even from the same agency. The City and County of Denver Open Data Portal distributes several types of geospatial datasets, one of them is the city parcels information containing 224,256 records. Although this data layer contains many pieces of information it is incomplete for some custom purposes. Open-Source Software were used to first collect data from diverse City of Denver Open Data sets, then upload them to a repository in the Cloud where they were processed using a PostgreSQL installation on the Cloud and Python scripts. Our method was able to extract non-spatial information from a ‘not-ready-to-download’ source that could then be combined with the initial data set to enhance its potential use.

  8. Global OpenSearch

    Science.gov (United States)

    Newman, D. J.; Mitchell, A. E.

    2015-12-01

    At AGU 2014, NASA EOSDIS demonstrated a case-study of an OpenSearch framework for Earth science data discovery. That framework leverages the IDN and CWIC OpenSearch API implementations to provide seamless discovery of data through the 'two-step' discovery process as outlined by the Federation for Earth Sciences (ESIP) OpenSearch Best Practices. But how would an Earth Scientist leverage this framework and what are the benefits? Using a client that understands the OpenSearch specification and, for further clarity, the various best practices and extensions, a scientist can discovery a plethora of data not normally accessible either by traditional methods (NASA Earth Data Search, Reverb, etc) or direct methods (going to the source of the data) We will demonstrate, via the CWICSmart web client, how an earth scientist can access regional data on a regional phenomena in a uniform and aggregated manner. We will demonstrate how an earth scientist can 'globalize' their discovery. You want to find local data on 'sea surface temperature of the Indian Ocean'? We can help you with that. 'European meteorological data'? Yes. 'Brazilian rainforest satellite imagery'? That too. CWIC allows you to get earth science data in a uniform fashion from a large number of disparate, world-wide agencies. This is what we mean by Global OpenSearch.

  9. Open development networked innovations in international development

    CERN Document Server

    Reilly, Katherine M A

    2014-01-01

    The emergence of open networked models made possible by digital technology has the potential to transform international development. Open network structures allow people to come together to share information, organize, and collaborate. Open development harnesses this power, to create new organizational forms and improve people's lives; it is not only an agenda for research and practice but also a statement about how to approach international development. In this volume, experts explore a variety of applications of openness, addressing challenges as well as opportunities. Open development requires new theoretical tools that focus on real world problems, consider a variety of solutions, and recognize the complexity of local contexts. After exploring the new theoretical terrain, the book describes a range of cases in which open models address such specific development issues as biotechnology research, improving education, and access to scholarly publications. Contributors then examine tensions between open model...

  10. Tip opening of premixed bunsen flames: Extinction with negative stretch and local Karlovitz number

    KAUST Repository

    Vu, Tranmanh; Cha, Min; Lee, Byeongjun; Chung, Suk-Ho

    2015-01-01

    The characteristics of tip openings in premixed bunsen flames have been studied experimentally by measuring OH radicals from laser-induced fluorescence and tip curvatures from chemiluminescent images. Results showed that the tip opening occurred

  11. Lipopolysaccharide precipitates hepatic encephalopathy and increases blood-brain barrier permeability in mice with acute liver failure.

    Science.gov (United States)

    Chastre, Anne; Bélanger, Mireille; Nguyen, Bich N; Butterworth, Roger F

    2014-03-01

    Acute liver failure (ALF) is frequently complicated by infection leading to precipitation of central nervous system complications such as hepatic encephalopathy (HE) and increased mortality. There is evidence to suggest that when infection occurs in ALF patients, the resulting pro-inflammatory mechanisms may be amplified that could, in turn, have a major impact on blood-brain barrier (BBB) function. The aim of this study was to investigate the role of endotoxemia on the progression of encephalopathy in relation to BBB permeability during ALF. Adult male C57-BL6 mice with ALF resulting from azoxymethane-induced toxic liver injury were administered trace amounts of the endotoxin component lipopolysaccharide (LPS). Effects on the magnitude of the systemic inflammatory response, liver pathology and BBB integrity were measured as a function of progression of HE, defined as time to loss of corneal reflex (coma). Lipopolysaccharide caused additional two- to seven-fold (P liver pathology and associated increases of circulating transaminases as well as increased hyperammonaemia consistent with a further loss of viable hepatocytes. LPS treatment of ALF mice led to a rapid precipitation of hepatic coma and the BBB became permeable to the 25-kDa protein immunoglobulin G (IgG). This extravasation of IgG was accompanied by ignificant up-regulation of matrix metalloproteinase-9 (MMP-9), an endopeptidase known to modulate opening of the BBB in a wide range of neurological disorders. These findings represent the first direct evidence of inflammation-related BBB permeability changes in ALF. © 2013 John Wiley & Sons A/S. Publishing by John Wiley & Sons Ltd.

  12. Quality of Public Open Spaces and Recreational Walking.

    Science.gov (United States)

    Sugiyama, Takemi; Gunn, Lucy D; Christian, Hayley; Francis, Jacinta; Foster, Sarah; Hooper, Paula; Owen, Neville; Giles-Corti, Billie

    2015-12-01

    We examined associations between specific public open space (POS) attributes and recreational walking to local POS. Between October 2004 and December 2006, 1465 adults of the RESIDential Environments Project, conducted in Perth, Australia, reported whether they walk to a POS for recreation. For each participant, we identified all open spaces larger than 0.8 hectares within 1.6 kilometers from home. On the basis of field audit data, we created 3 scores (presence, count, size-weighted presence) for 19 specific open space attributes. With logistic regression analyses, we found that walking to a POS was associated with the presence of gardens, grassed areas, walking paths, water features, wildlife, amenities, dog-related facilities, and off-leash areas for dogs. It was also associated with the highest number of these attributes in a single open space, but not with the total number of attributes in all POSs within 1.6 kilometers of home. Building 1 high-quality local park may be more effective in promoting recreational walking than is providing many average-quality parks.

  13. Adjustment of legally binding local plans

    DEFF Research Database (Denmark)

    Hvingel, Line Træholt; Aunsborg, Christian; Christensen, Finn Kjær

    2012-01-01

    Traditionally, and by law, new urban areas in Denmark are regulated and planned through legally binding local plans. Recently a tendency has occurred: The municipalities make the legally binding local plans quite open for future adjustment, and they are using a substantial amount of ‘empowerment ...... the considerations of legal rights, the extend of the legal use of empowerment provisions and the combination of the use of legal binding local plans and other legal instruments such as easements and sales agreements.......Traditionally, and by law, new urban areas in Denmark are regulated and planned through legally binding local plans. Recently a tendency has occurred: The municipalities make the legally binding local plans quite open for future adjustment, and they are using a substantial amount of ‘empowerment...... provisions’ which empower the municipalities to later ruling. This way of making plans postpones the actual regulation of an area (i.e. the planning permission) making it an individual ruling for instance at the application of building permits. Case studies show examples of this way of regulating an area...

  14. Open Data Day Hackathon 2014 at Edmonton Public Library

    Directory of Open Access Journals (Sweden)

    Alex Carruthers

    2014-12-01

    Full Text Available Edmonton Public Library (EPL hosted its first hackathon for International Open Data Day 2014. International Open Data Day promotes open data policies in local, regional, and national governments worldwide, in the spirit of transparency and civic innovation. The open data movement, like public libraries, values access to information and civic engagement, and it offers opportunities for public libraries to improve their efficiency, transparency, and programming. Celebrating the event provided the Library with the additional benefit of strengthening our relationship to local government. This case study provides a practical introduction to hosting an open data hackathon as a first step to engaging the open data movement. Two follow-up surveys, one immediately after the hackathon and another five months later, were used to assess the event and determine how the Library could better support the open data community in the future. The majority of hackathon participants labelled themselves beginner programmers, were not regular library users, and appreciated the opportunity to meet city employees and other hackers who shared their interests. The Library was encouraged to increase our output of open data and to host more hackathons. Results also suggested room for improvement in the areas of developing a more formal structure to the event, connecting participants with similar interests, and providing long term support for app development. By hosting a hackathon for International Open Data Day, EPL gained both the information and the relationships necessary to release meaningful datasets and put itself in an excellent position to understand and respond to the interests and needs of the open data community.

  15. Local energy losses at positive and negative steps in subcritical ...

    African Journals Online (AJOL)

    Local energy losses occur when there is a transition in open channel flow. Even though local losses in subcritical open channel flow due to changes in channel width have been studied, to date no studies have been reported for losses due to changes in bed elevations. Steps are commonly used in engineering applications ...

  16. Modeling localized delivery of Doxorubicin to the brain following focused ultrasound enhanced blood-brain barrier permeability

    International Nuclear Information System (INIS)

    Nhan, Tam; Burgess, Alison; Hynynen, Kullervo; Lilge, Lothar

    2014-01-01

    Doxorubicin (Dox) is a well-established chemotherapeutic agent, however it has limited efficacy in treating brain malignancies due to the presence of the blood-brain barrier (BBB). Recent preclinical studies have demonstrated that focused ultrasound induced BBB disruption (BBBD) enables efficient delivery of Dox to the brain. For future treatment planning of BBBD-based drug delivery, it is crucial to establish a mathematical framework to predict the effect of transient BBB permeability enhancement on the spatiotemporal distribution of Dox at the targeted area. The constructed model considers Dox concentrations within three compartments (plasma, extracellular, intracellular) that are governed by various transport processes (e.g. diffusion in interstitial space, exchange across vessel wall, clearance by cerebral spinal fluid, uptake by brain cells). By examining several clinical treatment aspects (e.g. sonication scheme, permeability enhancement, injection mode), our simulation results support the experimental findings of optimal interval delay between two consecutive sonications and therapeutically-sufficient intracellular concentration with respect to transfer constant K trans range of 0.01–0.03 min −1 . Finally, the model suggests that infusion over a short duration (20–60 min) should be employed along with single-sonication or multiple-sonication at 10 min interval to ensure maximum delivery to the intracellular compartment while attaining minimal cardiotoxicity via suppressing peak plasma concentration. (paper)

  17. Article Processing Charges and OpenAPC

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    The publication landscape is about to change. While being largely operated by subscription based journals in the past, recent political decisions force the publishing industry towards OpenAccess. Especially, the publication of the Finch report in 2012 put APC based Gold OpenAccess models almost everywhere on the agenda. These models also require quite some adoptions for library work flows to handle payments, bills and centralized funds for publication fees. Sometimes handled in specialized systems (e.g. first setups in Jülich) pretty early on discussions started to handle APCs in local repositories which would also hold the OpenAccess content resulting from these fees, e.g. the University of Regenburg uses ePrints for this purpose. Backed up by the OpenData movmement, libraries also saw opportunity to exchange data about fees payed. Thus, OpenAPC.de was born in 2014 on github to facilitate this exchange and aggregate large amounts of data for evaluation and comparison. Using the repository to hold payment d...

  18. 48 CFR 614.402-70 - Waiver of public opening of bids.

    Science.gov (United States)

    2010-10-01

    ... of public opening of bids. Overseas posts may request waiver of the public opening of bids if that activity is inconsistent with local law or legal practice, or with post security. For that purpose, the...

  19. Fractionated BNCT for locally recurrent head and neck cancer: Experience from a phase I/II clinical trial at Tsing Hua Open-Pool Reactor

    International Nuclear Information System (INIS)

    Wang, Ling-Wei; Chen, Yi-Wei; Ho, Ching-Yin; Hsueh Liu, Yen-Wan; Chou, Fong-In; Liu, Yuan-Hao; Liu, Hong-Ming; Peir, Jinn-Jer; Jiang, Shiang-Huei; Chang, Chi-Wei; Liu, Ching-Sheng; Wang, Shyh-Jen; Chu, Pen-Yuan; Yen, Sang-Hue

    2014-01-01

    To introduce our experience of treating locally and regionally recurrent head and neck cancer patients with BNCT at Tsing Hua Open-Pool Reactor in Taiwan, 12 patients (M/F=10/2, median age 55.5 Y/O) were enrolled and 11 received two fractions of treatment. Fractionated BNCT at 30-day interval with adaptive planning according to changed T/N ratios was feasible, effective and safe for selected recurrent head and neck cancer in this trial. - Highlights: • We treated 12 patients with recurrent Head and Neck (H and N) cancer after radical surgery and radiotherapy since 2010. • Four complete response (CR) and 3 partial response (PR) were found. Total response rate was 58%. • Two patients had local control longer than one year. • No grade 4 or higher toxicity was noted for both acute and chronic effects

  20. Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior

    Directory of Open Access Journals (Sweden)

    Samantha J. Hindle

    2017-10-01

    Full Text Available Summary: Central nervous system (CNS chemical protection depends upon discrete control of small-molecule access by the blood-brain barrier (BBB. Curiously, some drugs cause CNS side-effects despite negligible transit past the BBB. To investigate this phenomenon, we asked whether the highly BBB-enriched drug efflux transporter MDR1 has dual functions in controlling drug and endogenous molecule CNS homeostasis. If this is true, then brain-impermeable drugs could induce behavioral changes by affecting brain levels of endogenous molecules. Using computational, genetic, and pharmacologic approaches across diverse organisms, we demonstrate that BBB-localized efflux transporters are critical for regulating brain levels of endogenous steroids and steroid-regulated behaviors (sleep in Drosophila and anxiety in mice. Furthermore, we show that MDR1-interacting drugs are associated with anxiety-related behaviors in humans. We propose a general mechanism for common behavioral side effects of prescription drugs: pharmacologically challenging BBB efflux transporters disrupts brain levels of endogenous substrates and implicates the BBB in behavioral regulation. : Hindle et al. shed light on the curious finding that some drugs cause behavioral side-effects despite negligible access into the brain. These authors propose a unifying hypothesis that links blood-brain barrier drug transporter function and brain access of circulating steroids to common CNS adverse drug responses. Keywords: drug side effect mechanisms, central nervous system, blood brain barrier, behavior, toxicology, drug transporters, endobiotics, steroid hormones

  1. OpenAPC. Open-Access-Publikationskosten als Open Data

    OpenAIRE

    Tullney, Marco

    2015-01-01

    Präsentationsfolien zum Vortrag „OpenAPC. Open-Access-Publikationskosten als Open Data“ in der Session „Ausgestaltung eines wissenschaftsadäquaten APC-Marktes: Grundsätze, Finanzierungsansätze und Management“ der Open-Access-Tage 2015 in Zürich (https://www.open-access.net/community/open-access-tage/open-access-tage-2015-zuerich/programm/#c1974)

  2. OpenCL Performance Evaluation on Modern Multicore CPUs

    Directory of Open Access Journals (Sweden)

    Joo Hwan Lee

    2015-01-01

    Full Text Available Utilizing heterogeneous platforms for computation has become a general trend, making the portability issue important. OpenCL (Open Computing Language serves this purpose by enabling portable execution on heterogeneous architectures. However, unpredictable performance variation on different platforms has become a burden for programmers who write OpenCL applications. This is especially true for conventional multicore CPUs, since the performance of general OpenCL applications on CPUs lags behind the performance of their counterparts written in the conventional parallel programming model for CPUs. In this paper, we evaluate the performance of OpenCL applications on out-of-order multicore CPUs from the architectural perspective. We evaluate OpenCL applications on various aspects, including API overhead, scheduling overhead, instruction-level parallelism, address space, data location, data locality, and vectorization, comparing OpenCL to conventional parallel programming models for CPUs. Our evaluation indicates unique performance characteristics of OpenCL applications and also provides insight into the optimization metrics for better performance on CPUs.

  3. Influence of radiation on the blood-brain barrier and optimum time of chemotherapy

    International Nuclear Information System (INIS)

    Qin, D.X.; Zheng, R.; Tang, J.; Li, J.X.; Hu, Y.H.

    1990-01-01

    A pilot study of the destructive effects of radiation on the blood-brain barrier (BBB) was made on 14 patients with localized and limited brain tumors by 99MTc-GH imaging from August 1988 to November 1989. Count/pixel data were obtained from the unirradiated, irradiated, and tumor areas before and after radiotherapy of 30-40 Gy. It was observed that the BBB in the unirradiated area outside the radiation portal was not changed and the degree of destructive effect on the BBB in the irradiated normal area was directly proportional to the radiation dose. For 30-40 Gy, the count/pixel change enhances to average 24.7% [(147.6-118.4)/118.4], and (c) the BBB in the tumor area is partially destroyed on an average of 22.1% [(206.8-169.4)/169.4] by the tumor. The radiotherapy further enhances this effect to an average of 74.7% [(206.8-118.4)/118.4]. Case 3 showed that before radiation, the degree of destructive effect on the BBB in the tumor area was 22% [(167-137)/137] higher than normal brain tissue. After a dose of 30 Gy of irradiation, it increased to 76.7% [(242-137)/137]; 8 months later it decreased to 17% [(160.3-137)/137]. It has been proven that the BBB can recover at least partially. Based on these observations, the authors believe that in the combined treatment of operated brain tumors, radiotherapy should precede chemotherapy so as to enhance the destruction of the BBB, facilitating the incorporation of drugs into the tumor. The dose at which to start chemotherapy is 20-30 Gy

  4. 75 FR 23587 - Annual Seattle Yacht Club's “Opening Day” Marine Parade

    Science.gov (United States)

    2010-05-04

    ... Seattle Yacht Club's ``Opening Day'' Marine Parade AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement..., Portage Cut (Montlake Cut), and Union Bay, WA during the Annual Seattle Yacht Club's ``Opening Day... Special Local Regulation for the annual Seattle Yacht Club's ``Opening Day'' Marine Parade in 33 CFR 100...

  5. In a situation of incomprehension, a very opened process is necessary where the local dimension is the key

    International Nuclear Information System (INIS)

    Le Bars, Y.

    2003-01-01

    First and foremost, it is important to note the largely diverging opinions between specialists and the public on the current state of radioactive-waste management. The lack of a common understanding of what may constitute a waste-induced risk complicates any social negotiation pertaining to risk. In order to proceed towards solutions that are respectful of the long term, the countries concerned have implemented procedures that share many features in common. By selecting a stepwise approach - that is fully in line with the reversibility principle - it is possible to structure the different levels and policies, while allowing for ongoing observation and apprenticeship. The clear identification of the role of the different actors, as well as their behaviours, constitute the key elements for reinforcing their confidence. The local dimension of the procedure is essential and, even more in France, since she remains the only country in the world to investigate the feasibility of waste repositories outside areas that are already familiar with nuclear energy. Three guarantees must be provided: understanding the safety of the facilities, applying equity in the site-selection process while integrating development incentives in the projects, and ensuring an open local debate. Under those conditions, it is likely that appropriate means will be defined to manage radioactive waste over the long term while respecting the principle of sustainable development. (author)

  6. Open Standards, Open Source, and Open Innovation: Harnessing the Benefits of Openness

    Science.gov (United States)

    Committee for Economic Development, 2006

    2006-01-01

    Digitization of information and the Internet have profoundly expanded the capacity for openness. This report details the benefits of openness in three areas--open standards, open-source software, and open innovation--and examines the major issues in the debate over whether openness should be encouraged or not. The report explains each of these…

  7. Build back better principles for economic recovery: case study of the Victorian bushfires.

    Science.gov (United States)

    Mannakkara, Sandeeka; Wilkinson, Suzanne

    This paper looks at developing build back better (BBB) principles for economic recovery using the 2009 Victorian bushfires in Australia as a case study. The concept behind BBB-based economic recovery is to rejuvenate the economy in disaster-affected communities along with rebuilding to create resilient sustainable communities. A review of the literature identified several principles that can be applied to economic recovery to build back better. Data were collected in 2010 and 2011 by conducting semi- structured interviews with stakeholders who were directly involved in the Victorian bushfires recovery efforts, along with reports and other documentation. The recovery in Victoria displayed the use of BBB-based initiatives for economic recovery. The successes and shortcomings contributed to the creation of a modified list of BBB principles for economic recovery, including: creating an economic strategy based on thorough data collection; providing effective funding through grants and flexible low-interest loans; establishing business advice and mentoring services; providing incentives for businesses; assisting speedy rebuilding of business buildings; providing subsidised employee training and up-skilling programmes; and promoting local businesses through advertising.

  8. Disruption in the Blood-Brain Barrier: The Missing Link between Brain and Body Inflammation in Bipolar Disorder?

    Directory of Open Access Journals (Sweden)

    Jay P. Patel

    2015-01-01

    Full Text Available The blood-brain barrier (BBB regulates the transport of micro- and macromolecules between the peripheral blood and the central nervous system (CNS in order to maintain optimal levels of essential nutrients and neurotransmitters in the brain. In addition, the BBB plays a critical role protecting the CNS against neurotoxins. There has been growing evidence that BBB disruption is associated with brain inflammatory conditions such as Alzheimer’s disease and multiple sclerosis. Considering the increasing role of inflammation and oxidative stress in the pathophysiology of bipolar disorder (BD, here we propose a novel model wherein transient or persistent disruption of BBB integrity is associated with decreased CNS protection and increased permeability of proinflammatory (e.g., cytokines, reactive oxygen species substances from the peripheral blood into the brain. These events would trigger the activation of microglial cells and promote localized damage to oligodendrocytes and the myelin sheath, ultimately compromising myelination and the integrity of neural circuits. The potential implications for research in this area and directions for future studies are discussed.

  9. A Transparent Runtime Data Distribution Engine for OpenMP

    Directory of Open Access Journals (Sweden)

    Dimitrios S. Nikolopoulos

    2000-01-01

    Full Text Available This paper makes two important contributions. First, the paper investigates the performance implications of data placement in OpenMP programs running on modern NUMA multiprocessors. Data locality and minimization of the rate of remote memory accesses are critical for sustaining high performance on these systems. We show that due to the low remote-to-local memory access latency ratio of contemporary NUMA architectures, reasonably balanced page placement schemes, such as round-robin or random distribution, incur modest performance losses. Second, the paper presents a transparent, user-level page migration engine with an ability to gain back any performance loss that stems from suboptimal placement of pages in iterative OpenMP programs. The main body of the paper describes how our OpenMP runtime environment uses page migration for implementing implicit data distribution and redistribution schemes without programmer intervention. Our experimental results verify the effectiveness of the proposed framework and provide a proof of concept that it is not necessary to introduce data distribution directives in OpenMP and warrant the simplicity or the portability of the programming model.

  10. Nanoparticle-Based Strategies to Treat Neuro-Inflammation

    Directory of Open Access Journals (Sweden)

    Rémy Poupot

    2018-02-01

    Full Text Available Neuro-inflammation is a pivotal physio-pathological feature of brain disorders, including neurodegenerative diseases. As such, it is a relevant therapeutic target against which drugs have to be proposed. Targeting neuro-inflammation implies crossing the Blood-Brain Barrier (BBB to reach the Central Nervous System (CNS. Engineered nanoparticles (ENPs are promising candidates to carry and deliver drugs to the CNS by crossing the BBB. There are several strategies to design ENPs intended for crossing through the BBB. Herein, we first put nanotechnologies back in their historical context and introduce neuro-inflammation and its consequences in terms of public health. In a second part, we explain how ENPs can get access to the brain and review this area by highlighting recent papers in the field. Finally, after pointing out potential guidelines for preclinical studies involving ENPs, we conclude by opening the debate on the questions of nanosafety and toxicity of these ENPs and in particular on ecotoxicity related to regulatory issues and public concerns.

  11. GODAN Local Farming Challenge 2017 - Encourage Geo-Innovation Solutions for Zero Hunger

    Science.gov (United States)

    Anand, Suchith; Hogan, Patrick; Brovelli, Maria; Schaap, Ben; Musker, Ruthie; Laperrière, André

    2017-04-01

    The initial ideas for Open Geospatial Science [1] were presented nearly a decade ago. They build upon the proposition of Open science which argues that scientific knowledge develops more rapidly and productively if openly shared (as early as is practical in the discovery process). The key ingredients that make Open Geospatial Science possible are enshrined in Open Principles, i.e.: open source geospatial software, open data, open standards, open educational resources, and open access to research publications. OpenCitySmart[2] is an initiative of Geo for All [3] that aims to develop a suite of tools for city-related infrastructure management (utilities, traffic, services, etc.). Its purpose will be to continually refine and add functionality that not only streamlines operational efficiency but also considers the need for sustainability and quality of urban life. OpenCitySmart employs Open solutions to build richer tools that empower organisations and individuals to utilizespatial and non-spatial data alike. This will create opportunities for innovation both globally and locally. As the population of cities grow, the concern of food security will shift from rural to urban areas. Currently, nearly 800 million people struggle with debilitating hunger and malnutrition and can be found in every corner of the globe. That's one in every nine people, with the majority being women and children. The Global Open Data for Agriculture and Nutrition (GODAN) [4] supports the proactive sharing of open data to make information about agriculture and nutrition available, accessible and usable to deal with the urgent challenge of ensuring world food security. A core principle behind GODAN is that a solution to Zero Hunger lies within existing, but often unavailable, agriculture and nutrition data. Through an online survey, GODAN found that the most needed data type across its 430+ partner network was geospatial data. Through the GODAN Europa Challenge we want to bring together

  12. An open ecosystem engagement strategy through the lens of global food safety

    Science.gov (United States)

    Stacey, Paul; Fons, Garin; Bernardo, Theresa M

    2015-01-01

    The Global Food Safety Partnership (GFSP) is a public/private partnership established through the World Bank to improve food safety systems through a globally coordinated and locally-driven approach. This concept paper aims to establish a framework to help GFSP fully leverage the potential of open models. In preparing this paper the authors spoke to many different GFSP stakeholders who asked questions about open models such as: what is it?what’s in it for me?why use an open rather than a proprietary model?how will open models generate equivalent or greater sustainable revenue streams compared to the current “traditional” approaches?  This last question came up many times with assertions that traditional service providers need to see opportunity for equivalent or greater revenue dollars before they will buy-in. This paper identifies open value propositions for GFSP stakeholders and proposes a framework for creating and structuring that value. Open Educational Resources (OER) were the primary open practice GFSP partners spoke to us about, as they provide a logical entry point for collaboration. Going forward, funders should consider requiring that educational resources and concomitant data resulting from their sponsorship should be open, as a public good. There are, however, many other forms of open practice that bring value to the GFSP. Nine different open strategies and tactics (Appendix A) are described, including: open content (including OER and open courseware), open data, open access (research), open government, open source software, open standards, open policy, open licensing and open hardware. It is recommended that all stakeholders proactively pursue "openness" as an operating principle. This paper presents an overall GFSP Open Ecosystem Engagement Strategy within which specific local case examples can be situated. Two different case examples, China and Colombia, are presented to show both project-based and crowd-sourced, direct-to-public paths

  13. Effect of the decommissioned Roger open dump, João Pessoa, Brazil, on local groundwater quality

    Directory of Open Access Journals (Sweden)

    Giulliano de Souza Fagundes

    2009-04-01

    Full Text Available Throughout 45 years (1958-2003 the solid wastes from João Pessoa were disposed off in the former Roger’s open dump, which is situated adjacent to the mangrove at the sides of Sanhauá river, intensifying environmental problems and threatening the health of people living nearby. Between 1999 and 2003 the decommissioned open dump received wastes from the cities of Cabedelo and Bayeux. Several environmental impacts result from this inadequate disposal of solid wastes, including the pollution of groundwater nearby the former Roger´s open dump, which is the major point of investigation of this paper. The water quality of 6 wells situated in the region of influence of the open dump were monitored. Results have shown that the groundwater near the open dump cannot be drunk by the population without previous treatment, since it has some parameters of water quality in discordance with Brazilian legislation concerned with drinking water. Results have also shown that the level of pollution is higher in the wells closer to the open dump.

  14. OpenQ∗D simulation code for QCD+QED

    DEFF Research Database (Denmark)

    Campos, Isabel; Fritzsch, Patrick; Hansen, Martin

    2018-01-01

    The openQ∗D code for the simulation of QCD+QED with C∗ boundary conditions is presented. This code is based on openQCD-1.6, from which it inherits the core features that ensure its efficiency: the locally-deflated SAP-preconditioned GCR solver, the twisted-mass frequency splitting of the fermion....... An alpha version of this code is publicly available and can be downloaded from http://rcstar.web.cern.ch/....

  15. Generalizations of γ-open set in topological spaces

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Baby, E-mail: babybhatt75@gmail.com; Paul, Arnab, E-mail: mrarnabpaul87@gmail.com [Department of Mathematics, NIT Agartala, Jirania, Tripura (India)

    2016-06-21

    The main aim of this work is to study three generalized forms of γ-open set due to D. Andrijevic (D. Andrijevic, On the Topology Generated by pre-open sets, Presented at the Sixth Prague Topological Symposium, 39 (1987), 367-376)in a topological space. Out of which the dual appearance of one is the stronger form of b-locally closed set in the sense of Arafa A. Nasef (A. A Nasef,On b-locally closed sets and related topics, CHAOS SOLITONS & FRACTALS 12(2001) 1909-1915). Also, we introduce the concept of different types of continuity and study their basic properties by using these newly defined sets. Finally, we establish the interrelationships among themselves together with some already existing generalized forms of continuity.

  16. Pressure-driven opening of carbon nanotubes

    Science.gov (United States)

    Chaban, Vitaly V.; Prezhdo, Oleg V.

    2016-03-01

    The closing and opening of carbon nanotubes (CNTs) is essential for their applications in nanoscale chemistry and biology. We report reactive molecular dynamics simulations of CNT opening triggered by internal pressure of encapsulated gas molecules. Confined argon generates 4000 bars of pressure inside capped CNT and lowers the opening temperature by 200 K. Chemical interactions greatly enhance the efficiency of CNT opening: fluorine-filled CNTs open by fluorination of carbon bonds at temperature and pressure that are 700 K and 1000 bar lower than for argon-filled CNTs. Moreover, pressure induced CNT opening by confined gases leaves the CNT cylinders intact and removes only the fullerene caps, while the empty CNT decomposes completely. In practice, the increase in pressure can be achieved by near-infrared light, which penetrates through water and biological tissues and is absorbed by CNTs, resulting in rapid local heating. Spanning over a thousand of bars and Kelvin, the reactive and non-reactive scenarios of CNT opening represent extreme cases and allow for a broad experimental control over properties of the CNT interior and release conditions of the confined species. The detailed insights into the thermodynamic conditions and chemical mechanisms of the pressure-induced CNT opening provide practical guidelines for the development of novel nanoreactors, catalysts, photo-catalysts, imaging labels and drug delivery vehicles.

  17. The Green-Kubo formula for locally interacting fermionic open systems

    CERN Document Server

    Jaksic, V; Pillet, C A

    2006-01-01

    We consider a model describing finitely many free Fermi gas reservoirs coupled by local interactions and prove the Green-Kubo formulas and the Onsager reciprocity relations for heat and charge fluxes generated by temperature and chemical potential differentials.

  18. Transfer closed and transfer open multimaps in minimal spaces

    International Nuclear Information System (INIS)

    Alimohammady, M.; Roohi, M.; Delavar, M.R.

    2009-01-01

    This paper is devoted to introduce the concepts of transfer closed and transfer open multimaps in minimal spaces. Also, some characterizations of them are considered. Further, the notion of minimal local intersection property will be introduced and characterized. Moreover, some maximal element theorems via minimal transfer closed multimaps and minimal local intersection property are given.

  19. A Comparative Study on Metadata Scheme of Chinese and American Open Data Platforms

    Directory of Open Access Journals (Sweden)

    Yang Sinan

    2018-01-01

    Full Text Available [Purpose/significance] Open government data is conducive to the rational development and utilization of data resources. It can encourage social innovation and promote economic development. Besides, in order to ensure effective utilization and social increment of open government data, high-quality metadata schemes is necessary. [Method/process] Firstly, this paper analyzed the related research of open government data at home and abroad. Then, it investigated the open metadata schemes of some Chinese main local governments’ data platforms, and made a comparison with the metadata standard of American open government data. [Result/conclusion] This paper reveals that there are some disadvantages about Chinese local government open data affect the use effect of open data, which including that different governments use different data metadata schemes, the description of data set is too simple for further utilization and usually presented in HTML Web page format with lower machine-readable. Therefore, our government should come up with a standardized metadata schemes by drawing on the international mature and effective metadata standard, to ensure the social needs of high quality and high value data.

  20. Computational Prediction of Blood-Brain Barrier Permeability Using Decision Tree Induction

    Directory of Open Access Journals (Sweden)

    Jörg Huwyler

    2012-08-01

    Full Text Available Predicting blood-brain barrier (BBB permeability is essential to drug development, as a molecule cannot exhibit pharmacological activity within the brain parenchyma without first transiting this barrier. Understanding the process of permeation, however, is complicated by a combination of both limited passive diffusion and active transport. Our aim here was to establish predictive models for BBB drug permeation that include both active and passive transport. A database of 153 compounds was compiled using in vivo surface permeability product (logPS values in rats as a quantitative parameter for BBB permeability. The open source Chemical Development Kit (CDK was used to calculate physico-chemical properties and descriptors. Predictive computational models were implemented by machine learning paradigms (decision tree induction on both descriptor sets. Models with a corrected classification rate (CCR of 90% were established. Mechanistic insight into BBB transport was provided by an Ant Colony Optimization (ACO-based binary classifier analysis to identify the most predictive chemical substructures. Decision trees revealed descriptors of lipophilicity (aLogP and charge (polar surface area, which were also previously described in models of passive diffusion. However, measures of molecular geometry and connectivity were found to be related to an active drug transport component.

  1. Outcome of patients undergoing open heart surgery at the Uganda heart institute, Mulago hospital complex.

    Science.gov (United States)

    Aliku, Twalib O; Lubega, Sulaiman; Lwabi, Peter; Oketcho, Michael; Omagino, John O; Mwambu, Tom

    2014-12-01

    Heart disease is a disabling condition and necessary surgical intervention is often lacking in many developing countries. Training of the superspecialties abroad is largely limited to observation with little or no opportunity for hands on experience. An approach in which open heart surgeries are conducted locally by visiting teams enabling skills transfer to the local team and helps build to build capacity has been adopted at the Uganda Heart Institute (UHI). We reviewed the progress of open heart surgery at the UHI and evaluated the postoperative outcomes and challenges faced in conducting open heart surgery in a developing country. Medical records of patients undergoing open heart surgery at the UHI from October 2007 to June 2012 were reviewed. A total of 124 patients underwent open heart surgery during the study period. The commonest conditions were: venticular septal defects (VSDs) 34.7% (43/124), Atrial septal defects (ASDs) 34.7% (43/124) and tetralogy of fallot (TOF) in 10.5% (13/124). Non governmental organizations (NGOs) funded 96.8% (120/124) of the operations, and in only 4 patients (3.2%) families paid for the surgeries. There was increasing complexity in cases operated upon from predominantly ASDs and VSDs at the beginning to more complex cases like TOFs and TAPVR. The local team independently operated 19 patients (15.3%). Postoperative morbidity was low with arrhythmias, left ventricular dysfunction and re-operations being the commonest seen. Post operative sepsis occurred in only 2 cases (1.6%). The overall mortality rate was 3.2. Open heart surgery though expensive is feasible in a developing country. With increased direct funding from governments and local charities to support open heart surgeries, more cardiac patients access surgical treatment locally.

  2. Safe and stable noninvasive focal gene delivery to the mammalian brain following focused ultrasound.

    Science.gov (United States)

    Stavarache, Mihaela A; Petersen, Nicholas; Jurgens, Eric M; Milstein, Elizabeth R; Rosenfeld, Zachary B; Ballon, Douglas J; Kaplitt, Michael G

    2018-04-27

    OBJECTIVE Surgical infusion of gene therapy vectors has provided opportunities for biological manipulation of specific brain circuits in both animal models and human patients. Transient focal opening of the blood-brain barrier (BBB) by MR-guided focused ultrasound (MRgFUS) raises the possibility of noninvasive CNS gene therapy to target precise brain regions. However, variable efficiency and short follow-up of studies to date, along with recent suggestions of the potential for immune reactions following MRgFUS BBB disruption, all raise questions regarding the viability of this approach for clinical translation. The objective of the current study was to evaluate the efficiency, safety, and long-term stability of MRgFUS-mediated noninvasive gene therapy in the mammalian brain. METHODS Focused ultrasound under the control of MRI, in combination with microbubbles consisting of albumin-coated gas microspheres, was applied to rat striatum, followed by intravenous infusion of an adeno-associated virus serotype 1/2 (AAV1/2) vector expressing green fluorescent protein (GFP) as a marker. Following recovery, animals were followed from several hours up to 15 months. Immunostaining for GFP quantified transduction efficiency and stability of expression. Quantification of neuronal markers was used to determine histological safety over time, while inflammatory markers were examined for evidence of immune responses. RESULTS Transitory disruption of the BBB by MRgFUS resulted in efficient delivery of the AAV1/2 vector to the targeted rodent striatum, with 50%-75% of striatal neurons transduced on average. GFP transgene expression appeared to be stable over extended periods of time, from 2 weeks to 6 months, with evidence of ongoing stable expression as long as 16 months in a smaller cohort of animals. No evidence of substantial toxicity, tissue injury, or neuronal loss was observed. While transient inflammation from BBB disruption alone was noted for the first few days, consistent

  3. Tissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid nanoparticles for delivery across the blood–brain barrier

    Directory of Open Access Journals (Sweden)

    Chaturvedi M

    2014-01-01

    Full Text Available Mayank Chaturvedi,1 Yves Molino,2 Bojja Sreedhar,3 Michel Khrestchatisky,4 Leszek Kaczmarek1 1Laboratory of Neurobiology, Nencki Institute, Warsaw, Poland; 2Vect-Horus, Marseille, France; 3Indian Institute of Chemical Technology, Hyderabad, India; 4Aix-Marseille Université, CNRS, NICN, UMR7259, Marseille, France Aim: The aim of this study was to develop poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs for delivery of a protein – tissue inhibitor of matrix metalloproteinases 1 (TIMP-1 – across the blood–brain barrier (BBB to inhibit deleterious matrix metalloproteinases (MMPs. Materials and methods: The NPs were formulated by multiple-emulsion solvent-evaporation, and for enhancing BBB penetration, they were coated with polysorbate 80 (Ps80. We compared Ps80-coated and uncoated NPs for their toxicity, binding, and BBB penetration on primary rat brain capillary endothelial cell cultures and the rat brain endothelial 4 cell line. These studies were followed by in vivo studies for brain delivery of these NPs. Results: Results showed that neither Ps80-coated nor uncoated NPs caused significant opening of the BBB, and essentially they were nontoxic. NPs without Ps80 coating had more binding to endothelial cells compared to Ps80-coated NPs. Penetration studies showed that TIMP-1 NPs + Ps80 had 11.21%±1.35% penetration, whereas TIMP-1 alone and TIMP-1 NPs without Ps80 coating did not cross the endothelial monolayer. In vivo studies indicated BBB penetration of intravenously injected TIMP-1 NPs + Ps80. Conclusion: The study demonstrated that Ps80 coating of NPs does not cause significant toxic effects to endothelial cells and that it can be used to enhance the delivery of protein across endothelial cell barriers, both in vitro and in vivo. Keywords: PLGA nanoparticles, drug delivery, protein delivery, sustained release, brain delivery, BBB penetration, RBCEC culture

  4. Dendritic cell CNS recruitment correlates with disease severity in EAE via CCL2 chemotaxis at the blood–brain barrier through paracellular transmigration and ERK activation

    Directory of Open Access Journals (Sweden)

    Sagar Divya

    2012-10-01

    Full Text Available Abstract Background Transmigration of circulating dendritic cells (DCs into the central nervous system (CNS across the blood–brain barrier (BBB has not thus far been investigated. An increase in immune cell infiltration across the BBB, uncontrolled activation and antigen presentation are influenced by chemokines. Chemokine ligand 2 (CCL2 is a potent chemoattractant known to be secreted by the BBB but has not been implicated in the recruitment of DCs specifically at the BBB. Methods Experimental autoimmune encephalomyelitis (EAE was induced in C57BL/6 mice by injection of MOG35–55 peptide and pertussis toxin intraperitoneally. Animals with increasing degree of EAE score were sacrificed and subjected to near-infrared and fluorescence imaging analysis to detect and localize the accumulation of CD11c+-labeled DCs with respect to CCL2 expression. To further characterize the direct effect of CCL2 in DC trafficking at the BBB, we utilized an in vitro BBB model consisting of human brain microvascular endothelial cells to compare migratory patterns of monocyte-derived dendritic cells, CD4+ and CD8+ T cells. Further, this model was used to image transmigration using fluorescence microcopy and to assess specific molecular signaling pathways involved in transmigration. Results Near-infrared imaging of DC transmigration correlated with the severity of inflammation during EAE. Ex vivo histology confirmed the presence of CCL2 in EAE lesions, with DCs emerging from perivascular spaces. DCs exhibited more efficient transmigration than T cells in BBB model studies. These observations correlated with transwell imaging, which indicated a paracellular versus transcellular pattern of migration by DCs and T cells. Moreover, at the molecular level, CCL2 seems to facilitate DC transmigration in an ERK1/2-dependent manner. Conclusion CNS recruitment of DCs correlates with disease severity in EAE via CCL2 chemotaxis and paracellular transmigration across the BBB

  5. Interfacing HTCondor-CE with OpenStack

    Science.gov (United States)

    Bockelman, B.; Caballero Bejar, J.; Hover, J.

    2017-10-01

    Over the past few years, Grid Computing technologies have reached a high level of maturity. One key aspect of this success has been the development and adoption of newer Compute Elements to interface the external Grid users with local batch systems. These new Compute Elements allow for better handling of jobs requirements and a more precise management of diverse local resources. However, despite this level of maturity, the Grid Computing world is lacking diversity in local execution platforms. As Grid Computing technologies have historically been driven by the needs of the High Energy Physics community, most resource providers run the platform (operating system version and architecture) that best suits the needs of their particular users. In parallel, the development of virtualization and cloud technologies has accelerated recently, making available a variety of solutions, both commercial and academic, proprietary and open source. Virtualization facilitates performing computational tasks on platforms not available at most computing sites. This work attempts to join the technologies, allowing users to interact with computing sites through one of the standard Computing Elements, HTCondor-CE, but running their jobs within VMs on a local cloud platform, OpenStack, when needed. The system will re-route, in a transparent way, end user jobs into dynamically-launched VM worker nodes when they have requirements that cannot be satisfied by the static local batch system nodes. Also, once the automated mechanisms are in place, it becomes straightforward to allow an end user to invoke a custom Virtual Machine at the site. This will allow cloud resources to be used without requiring the user to establish a separate account. Both scenarios are described in this work.

  6. September 2013: the doors open

    CERN Document Server

    Antonella Del Rosso

    2013-01-01

    Three special days and one public open day: at the end of September our Laboratory will open its doors to visitors from CERN, the local region and all over the world. With over 150,000 visitors expected in total, the organisation of the OpenDays is a challenge that a core team of eleven people have taken up with enthusiasm.   They come from several departments but share one goal: making the last four days of September an unforgettable experience for all the visitors who will come to discover the Laboratory and its scientists. The core team in charge of the organisation of the events is co-ordinated by Hermann Schmickler. “The events are an opportunity for us to celebrate  the discoveries, the excellent performance of the technical installations and the vital contribution of all the CERN personnel, the thousands of users and those working under support contracts,” says Hermann Schmickler. The four-day programme will start on Friday 27 September with an “...

  7. Toward Enhanced Access to Africa's Research and Local Content: A ...

    African Journals Online (AJOL)

    Institutional Repositories (IR) enhance access to institutional information resources that are of a local nature, and which also often focus on local issues. Also, the digital representation and availability of such local content through open access institutional repositories makes available to global researchers the information ...

  8. OpenNFT: An open-source Python/Matlab framework for real-time fMRI neurofeedback training based on activity, connectivity and multivariate pattern analysis.

    Science.gov (United States)

    Koush, Yury; Ashburner, John; Prilepin, Evgeny; Sladky, Ronald; Zeidman, Peter; Bibikov, Sergei; Scharnowski, Frank; Nikonorov, Artem; De Ville, Dimitri Van

    2017-08-01

    Neurofeedback based on real-time functional magnetic resonance imaging (rt-fMRI) is a novel and rapidly developing research field. It allows for training of voluntary control over localized brain activity and connectivity and has demonstrated promising clinical applications. Because of the rapid technical developments of MRI techniques and the availability of high-performance computing, new methodological advances in rt-fMRI neurofeedback become possible. Here we outline the core components of a novel open-source neurofeedback framework, termed Open NeuroFeedback Training (OpenNFT), which efficiently integrates these new developments. This framework is implemented using Python and Matlab source code to allow for diverse functionality, high modularity, and rapid extendibility of the software depending on the user's needs. In addition, it provides an easy interface to the functionality of Statistical Parametric Mapping (SPM) that is also open-source and one of the most widely used fMRI data analysis software. We demonstrate the functionality of our new framework by describing case studies that include neurofeedback protocols based on brain activity levels, effective connectivity models, and pattern classification approaches. This open-source initiative provides a suitable framework to actively engage in the development of novel neurofeedback approaches, so that local methodological developments can be easily made accessible to a wider range of users. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Two faces of global open society

    Directory of Open Access Journals (Sweden)

    Cvetićanin Neven

    2008-01-01

    Full Text Available The Essay considers 'the rule' of the so called post-civil political centre that corresponds to the familiar concept of open society, questioning the good as well as the bad sides of such 'rule'. The research is in the first place about global open society stability and attention is addressed to its present enemies - from terrorism, over organized crime, all the way to the so called local legitimates that are confronting the universal and global legitimates represented by the followers of the open society from the post civil political centre area. The Essay presents the debate with Fukuyama's thesis about the 'end of history' considering that open society, i.e. global post civil political centre has visible enemies who do not allow for dialectics of history to stand still as Fukuyama believed. Instead of Fukuyama's 'end of history' the Essay comes to the conclusion that present global situation is marked by post-modern opposition of liberal-democratic post civil centre and extreme anti civil margins, with reference to the opposition of open society and its enemies, which will put under limits further steps of history towards new socio-historical forms.

  10. Impacts of a lengthening open water season on Alaskan coastal communities: deriving locally relevant indices from large-scale datasets and community observations

    Science.gov (United States)

    Rolph, Rebecca J.; Mahoney, Andrew R.; Walsh, John; Loring, Philip A.

    2018-05-01

    Using thresholds of physical climate variables developed from community observations, together with two large-scale datasets, we have produced local indices directly relevant to the impacts of a reduced sea ice cover on Alaska coastal communities. The indices include the number of false freeze-ups defined by transient exceedances of ice concentration prior to a corresponding exceedance that persists, false break-ups, timing of freeze-up and break-up, length of the open water duration, number of days when the winds preclude hunting via boat (wind speed threshold exceedances), the number of wind events conducive to geomorphological work or damage to infrastructure from ocean waves, and the number of these wind events with on- and along-shore components promoting water setup along the coastline. We demonstrate how community observations can inform use of large-scale datasets to derive these locally relevant indices. The two primary large-scale datasets are the Historical Sea Ice Atlas for Alaska and the atmospheric output from a regional climate model used to downscale the ERA-Interim atmospheric reanalysis. We illustrate the variability and trends of these indices by application to the rural Alaska communities of Kotzebue, Shishmaref, and Utqiaġvik (previously Barrow), although the same procedure and metrics can be applied to other coastal communities. Over the 1979-2014 time period, there has been a marked increase in the number of combined false freeze-ups and false break-ups as well as the number of days too windy for hunting via boat for all three communities, especially Utqiaġvik. At Utqiaġvik, there has been an approximate tripling of the number of wind events conducive to coastline erosion from 1979 to 2014. We have also found a delay in freeze-up and earlier break-up, leading to a lengthened open water period for all of the communities examined.

  11. Impacts of a lengthening open water season on Alaskan coastal communities: deriving locally relevant indices from large-scale datasets and community observations

    Directory of Open Access Journals (Sweden)

    R. J. Rolph

    2018-05-01

    Full Text Available Using thresholds of physical climate variables developed from community observations, together with two large-scale datasets, we have produced local indices directly relevant to the impacts of a reduced sea ice cover on Alaska coastal communities. The indices include the number of false freeze-ups defined by transient exceedances of ice concentration prior to a corresponding exceedance that persists, false break-ups, timing of freeze-up and break-up, length of the open water duration, number of days when the winds preclude hunting via boat (wind speed threshold exceedances, the number of wind events conducive to geomorphological work or damage to infrastructure from ocean waves, and the number of these wind events with on- and along-shore components promoting water setup along the coastline. We demonstrate how community observations can inform use of large-scale datasets to derive these locally relevant indices. The two primary large-scale datasets are the Historical Sea Ice Atlas for Alaska and the atmospheric output from a regional climate model used to downscale the ERA-Interim atmospheric reanalysis. We illustrate the variability and trends of these indices by application to the rural Alaska communities of Kotzebue, Shishmaref, and Utqiaġvik (previously Barrow, although the same procedure and metrics can be applied to other coastal communities. Over the 1979–2014 time period, there has been a marked increase in the number of combined false freeze-ups and false break-ups as well as the number of days too windy for hunting via boat for all three communities, especially Utqiaġvik. At Utqiaġvik, there has been an approximate tripling of the number of wind events conducive to coastline erosion from 1979 to 2014. We have also found a delay in freeze-up and earlier break-up, leading to a lengthened open water period for all of the communities examined.

  12. Scrutinizing Open Government Data to Understand Patterns in eGovernment Uptake

    DEFF Research Database (Denmark)

    Zinner Henriksen, Helle

    2015-01-01

    reflects on the impact of communication via local print media and discusses the body of literature which focuses on print media as a vehicle for communication to citizens. The study opens for a discussion of how open government data-sets give new opportunities for generating scholarly insights but also how...

  13. Ebooks without Vendors: Using Open Source Software to Create and Share Meaningful Ebook Collections

    Directory of Open Access Journals (Sweden)

    Matt Weaver

    2014-07-01

    Full Text Available The Community Cookbook project began with wondering how to take local cookbooks in the library’s collection and create a recipe database. The final website is both a recipe website and collection of ebook versions of local cookbooks. This article will discuss the use of open source software at every stage in the project, which proves that an open source publishing model is possible for any library.

  14. The open letters of priest Feodor Vasilevsky to the all-Russia Church local Council of 1917–1918: about the sacrament of baptism and the destiny of the orthodoxy

    Directory of Open Access Journals (Sweden)

    Kail' Maksim

    2012-04-01

    Full Text Available The open letters of Smolensk priest Feodor Vasilevsky to the All-Russia Church Local Council werefound out in the Fund № 834 of the Holy Synod’s manuscripts atthe Russian state historical archive (RGIA. The letters not only display of intra-church discussions during the revolutionary time, but also represent the various typicalreflections which werecharacteristic for thefaith of provincial priests.

  15. Regulatory mechanisms for iron transport across the blood-brain barrier.

    Science.gov (United States)

    Duck, Kari A; Simpson, Ian A; Connor, James R

    2017-12-09

    Many critical metabolic functions in the brain require adequate and timely delivery of iron. However, most studies when considering brain iron uptake have ignored the iron requirements of the endothelial cells that form the blood-brain barrier (BBB). Moreover, current models of BBB iron transport do not address regional regulation of brain iron uptake or how neurons, when adapting to metabolic demands, can acquire more iron. In this study, we demonstrate that both iron-poor transferrin (apo-Tf) and the iron chelator, deferoxamine, stimulate release of iron from iron-loaded endothelial cells in an in vitro BBB model. The role of the endosomal divalent metal transporter 1 (DMT1) in BBB iron acquisition and transport has been questioned. Here, we show that inhibition of DMT1 alters the transport of iron and Tf across the endothelial cells. These data support an endosome-mediated model of Tf-bound iron uptake into the brain and identifies mechanisms for local regional regulation of brain iron uptake. Moreover, our data provide an explanation for the disparity in the ratio of Tf to iron transport into the brain that has confounded the field. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Open Source, Open Access, Open Review, Open Data. Initiativen zu mehr Offenheit in der digitalen Welt

    OpenAIRE

    Herb, Ulrich

    2011-01-01

    The article discusses the principles of openess, open access and open availability of information based on the examples of open access to scientific information, open government data, open geographical data and open source software.

  17. Optimization of Rear Local Al-Contacts on High Efficiency Commercial PERC Solar Cells with Dot and Line Openings

    Directory of Open Access Journals (Sweden)

    Peisheng Liu

    2014-01-01

    Full Text Available Crystalline silicon PERCs with dot or line openings on rear surface were studied here. By measuring the minor carrier lifetimes of the PERCs with dot and line openings, passivation effects of rear surface with dot and line openings were discussed. The performance affected by dot and line openings was analyzed in detail by testing the open-circuit voltages, short-circuit current densities, fill factors, and conversion efficiencies of the PERCs. The results show that the wider space resulted in better minor carrier lifetimes on the rear surface. And the cells with a line opening space of 0.5 mm had an average of 0.22% improvement of conversion efficiency, compared with the cells with full-area Al-BSF. On the other hand, the dot opening PERCs exhibited only a conversion efficiency of 17.4%, although there had been good rear surface reflectivity. The bad Al-Si alloy layer and large hollow densities in dot Al-contacts resulted in bad performance of the PERCs with dot openings.

  18. Open system LANs and their global interconnection electronics and communications reference series

    CERN Document Server

    Houldsworth, Jack; Caves, Keith; Mazda, FF

    2014-01-01

    Open System LANs and Their Global Interconnection focuses on the OSI layer 1 to 4 standards (the OSI bearer service) and also introduces TCP/IP and some of the proprietary PC Local Area Network (LAN) standards.The publication first provides an introduction to Local Area Networks (LANs) and Wide Area Networks (WANs), Open Systems Interconnection (OSI), and LAN standards. Discussions focus on MAC bridging, token bus, slotted ring, MAC constraints and design considerations, OSI functional standards, OSI model, value of the transport model, benefits and origins of OSI, and significance of the tran

  19. Local product structure for expansive homeomorphisms

    OpenAIRE

    Artigue, Alfonso; Brum, Joaquin; Potrie, Rafael

    2008-01-01

    Let $f\\colon M\\to M$ be an expansive homeomorphism with dense topologically hyperbolic periodic points, $M$ a compact manifold. Then there is a local product structure in an open and dense subset of $M$. Moreover, if some topologically hyperbolic periodic point has codimension one, then this local product structure is uniform. In particular, we conclude that the homeomorphism is conjugated to a linear Anosov diffeomorphism of a torus.

  20. Openly Published Environmental Sensing (OPEnS) | Advancing Open-Source Research, Instrumentation, and Dissemination

    Science.gov (United States)

    Udell, C.; Selker, J. S.

    2017-12-01

    The increasing availability and functionality of Open-Source software and hardware along with 3D printing, low-cost electronics, and proliferation of open-access resources for learning rapid prototyping are contributing to fundamental transformations and new technologies in environmental sensing. These tools invite reevaluation of time-tested methodologies and devices toward more efficient, reusable, and inexpensive alternatives. Building upon Open-Source design facilitates community engagement and invites a Do-It-Together (DIT) collaborative framework for research where solutions to complex problems may be crowd-sourced. However, barriers persist that prevent researchers from taking advantage of the capabilities afforded by open-source software, hardware, and rapid prototyping. Some of these include: requisite technical skillsets, knowledge of equipment capabilities, identifying inexpensive sources for materials, money, space, and time. A university MAKER space staffed by engineering students to assist researchers is one proposed solution to overcome many of these obstacles. This presentation investigates the unique capabilities the USDA-funded Openly Published Environmental Sensing (OPEnS) Lab affords researchers, within Oregon State and internationally, and the unique functions these types of initiatives support at the intersection of MAKER spaces, Open-Source academic research, and open-access dissemination.

  1. Open Data and Open Governance in Canada: A Critical Examination of New Opportunities and Old Tensions

    Directory of Open Access Journals (Sweden)

    Jeffrey Roy

    2014-06-01

    Full Text Available As governments develop open data strategies, such efforts reflect the advent of the Internet, the digitization of government, and the emergence of meta-data as a wider socio-economic and societal transformational. Within this context the purpose of this article is twofold. First, we seek to both situate and examine the evolution and effectiveness of open data strategies in the Canadian public sector, with a particular focus on municipal governments that have led this movement. Secondly, we delve more deeply into—if and how, open data can facilitate more open and innovative forms of governance enjoining an outward-oriented public sector (across all government levels with an empowered and participative society. This latter vantage point includes four main and inter-related dimensions: (i conceptualizing public value and public engagement; (ii media relations—across traditional intermediaries and channels and new social media; (iii political culture and the politics of privacy in an increasingly data-centric world; and (iv federated architectures and the alignment of localized, sub-national, and national strategies and governance mechanisms. This article demonstrates how each of these dimensions includes important determinants of not only open data’s immediate impacts but also its catalytic ability to forge wider and collective innovation and more holistic governance renewal.

  2. Market integration of local energy systems: Is local energy management compatible with European regulation for retail competition?

    OpenAIRE

    Eid, Cherrelle; Bollinger, L. Andrew; Koirala, Binod; Scholten, Daniel; Facchinetti, Emanuele; Lilliestam, Johan; Hakvoort, Rudi

    2016-01-01

    The growing penetration of distributed energy resources is opening up opportunities for local energy management (LEM) – the coordination of decentralized energy supply, storage, transport, conversion and consumption within a given geographical area. Because European electricity market liberalization concentrates competition at the wholesale level, local energy management at the distribution level is likely to impose new roles and responsibilities on existing and/or new actors. This paper prov...

  3. Provincial corruption and local development bank performance

    Directory of Open Access Journals (Sweden)

    Murharsito Murharsito

    2017-03-01

    Full Text Available This paper investigates the effect of provincial corruption on the performance of local development bank, specifically to the profitability and credit quality. We use the data of 26 local development banks in 2012 and 2013. For the provincial corruption measurement we use “Public Institution Openness Index”. Results of this study are first, corruption significantly has a negative effect on the profitability of local development bank. Second, corruption doesn’t affect the credit quality of local development bank. These results are expected to enrich the within country corruption effect to the economic studies, particularly to the local development bank which is infrequently investigated.

  4. Institutional and pedagogical criteria for productive open source learning environments

    DEFF Research Database (Denmark)

    Svendsen, Brian Møller; Ryberg, Thomas; Semey, Ian Peter

    2004-01-01

    In this article we present some institutional and pedagogical criteria for making an informed decision in relation to identifying and choosing a productive open source learning environment. We argue that three concepts (implementation, maintainability and further development) are important when...... considering the sustainability and cost efficiency of an open source system, and we outline a set of key points for evaluating an open source software in terms of cost of system adoption. Furthermore we identify a range of pedagogical concepts and criteria to emphasize the importance of considering...... the relation between the local pedagogical practice and the pedagogical design of the open source learning environment. This we illustrate through an analysis of an open source system and our own pedagogical practice at Aalborg University, Denmark (POPP)....

  5. Building Energy Management Open Source Software

    Energy Technology Data Exchange (ETDEWEB)

    2017-06-20

    This is the repository for Building Energy Management Open Source Software (BEMOSS), which is an open source operating system that is engineered to improve sensing and control of equipment in small- and medium-sized commercial buildings. BEMOSS offers the following key features: (1) Open source, open architecture – BEMOSS is an open source operating system that is built upon VOLTTRON – a distributed agent platform developed by Pacific Northwest National Laboratory (PNNL). BEMOSS was designed to make it easy for hardware manufacturers to seamlessly interface their devices with BEMOSS. Software developers can also contribute to adding additional BEMOSS functionalities and applications. (2) Plug & play – BEMOSS was designed to automatically discover supported load controllers (including smart thermostats, VAV/RTUs, lighting load controllers and plug load controllers) in commercial buildings. (3) Interoperability – BEMOSS was designed to work with load control devices form different manufacturers that operate on different communication technologies and data exchange protocols. (4) Cost effectiveness – Implementation of BEMOSS deemed to be cost-effective as it was built upon a robust open source platform that can operate on a low-cost single-board computer, such as Odroid. This feature could contribute to its rapid deployment in small- or medium-sized commercial buildings. (5) Scalability and ease of deployment – With its multi-node architecture, BEMOSS provides a distributed architecture where load controllers in a multi-floor and high occupancy building could be monitored and controlled by multiple single-board computers hosting BEMOSS. This makes it possible for a building engineer to deploy BEMOSS in one zone of a building, be comfortable with its operation, and later on expand the deployment to the entire building to make it more energy efficient. (6) Ability to provide local and remote monitoring – BEMOSS provides both local and remote monitoring

  6. Open science initiatives: challenges for public health promotion.

    Science.gov (United States)

    Holzmeyer, Cheryl

    2018-03-07

    While academic open access, open data and open science initiatives have proliferated in recent years, facilitating new research resources for health promotion, open initiatives are not one-size-fits-all. Health research particularly illustrates how open initiatives may serve various interests and ends. Open initiatives not only foster new pathways of research access; they also discipline research in new ways, especially when associated with new regimes of research use and peer review, while participating in innovation ecosystems that often perpetuate existing systemic biases toward commercial biomedicine. Currently, many open initiatives are more oriented toward biomedical research paradigms than paradigms associated with public health promotion, such as social determinants of health research. Moreover, open initiatives too often dovetail with, rather than challenge, neoliberal policy paradigms. Such initiatives are unlikely to transform existing health research landscapes and redress health inequities. In this context, attunement to social determinants of health research and community-based local knowledge is vital to orient open initiatives toward public health promotion and health equity. Such an approach calls for discourses, norms and innovation ecosystems that contest neoliberal policy frameworks and foster upstream interventions to promote health, beyond biomedical paradigms. This analysis highlights challenges and possibilities for leveraging open initiatives on behalf of a wider range of health research stakeholders, while emphasizing public health promotion, health equity and social justice as benchmarks of transformation.

  7. Open string T-duality in double space

    International Nuclear Information System (INIS)

    Sazdovic, B.

    2017-01-01

    The role of double space is essential in the new interpretation of T-duality and consequently in an attempt to construct M-theory. The case of the open string is missing in such an approach because until now there has been no appropriate formulation of open string T-duality. In the previous paper (Sazdovic, From geometry to non-geometry via T-duality, arXiv:1606.01938, 2017), we showed how to introduce vector gauge fields A"N_a and A"D_i at the end-points of an open string in order to enable open string invariance under local gauge transformations of the Kalb-Ramond field and its T-dual ''restricted general coordinate transformations''. We demonstrated that gauge fields A"N_a and A"D_i are T-dual to each other. In the present article we prove that all above results can be interpreted as coordinate permutations in double space. (orig.)

  8. Open string T-duality in double space

    Energy Technology Data Exchange (ETDEWEB)

    Sazdovic, B. [University of Belgrade, Institute of Physics, Belgrade (Serbia)

    2017-09-15

    The role of double space is essential in the new interpretation of T-duality and consequently in an attempt to construct M-theory. The case of the open string is missing in such an approach because until now there has been no appropriate formulation of open string T-duality. In the previous paper (Sazdovic, From geometry to non-geometry via T-duality, arXiv:1606.01938, 2017), we showed how to introduce vector gauge fields A{sup N}{sub a} and A{sup D}{sub i} at the end-points of an open string in order to enable open string invariance under local gauge transformations of the Kalb-Ramond field and its T-dual ''restricted general coordinate transformations''. We demonstrated that gauge fields A{sup N}{sub a} and A{sup D}{sub i} are T-dual to each other. In the present article we prove that all above results can be interpreted as coordinate permutations in double space. (orig.)

  9. Predicting Good Features for Image Geo-Localization Using Per-Bundle VLAD (Open Access)

    Science.gov (United States)

    2016-02-18

    the database, we propose per -bundle vector of locally aggregated de- scriptors (PBVLAD), where each maximally stable region is described by a vector of...a large area. We propose a per -bundle vector of locally aggregated descriptors (PBVLAD) for fea- ture representation, where each maximally stable

  10. Fusion Pore Diameter Regulation by Cations Modulating Local Membrane Anisotropy

    Directory of Open Access Journals (Sweden)

    Doron Kabaso

    2012-01-01

    Full Text Available The fusion pore is an aqueous channel that is formed upon the fusion of the vesicle membrane with the plasma membrane. Once the pore is open, it may close again (transient fusion or widen completely (full fusion to permit vesicle cargo discharge. While repetitive transient fusion pore openings of the vesicle with the plasma membrane have been observed in the absence of stimulation, their frequency can be further increased using a cAMP-increasing agent that drives the opening of nonspecific cation channels. Our model hypothesis is that the openings and closings of the fusion pore are driven by changes in the local concentration of cations in the connected vesicle. The proposed mechanism of fusion pore dynamics is considered as follows: when the fusion pore is closed or is extremely narrow, the accumulation of cations in the vesicle (increased cation concentration likely leads to lipid demixing at the fusion pore. This process may affect local membrane anisotropy, which reduces the spontaneous curvature and thus leads to the opening of the fusion pore. Based on the theory of membrane elasticity, we used a continuum model to explain the rhythmic opening and closing of the fusion pore.

  11. Open access, open education resources and open data in Uganda ...

    African Journals Online (AJOL)

    As a follow up to OpenCon 2014, International Federation of Medical Students' Associations (IFMSA) students organized a 3 day workshop Open Access, Open Education Resources and Open Data in Kampala from 15-18 December 2014. One of the aims of the workshop was to engage the Open Access movement in ...

  12. Post-operative pain relief using local infiltration analgesia during open abdominal hysterectomy: a randomized, double-blind study.

    Science.gov (United States)

    Hayden, J M; Oras, J; Karlsson, O I; Olausson, K G; Thörn, S-E; Gupta, A

    2017-05-01

    Post-operative pain is common and often severe after open abdominal hysterectomy, and analgesic consumption high. This study assessed the efficacy of local infiltration analgesia (LIA) injected systematically into different tissues during surgery compared with saline on post-operative pain and analgesia. Fifty-nine patients were randomized to Group LIA (n = 29) consisting of 156 ml of a mixture of 0.2% ropivacaine + 30 mg ketorolac + 0.5 mg (5 ml) adrenaline, where the drugs were injected systematically in the operating site, around the proximal vagina, the ligaments, in the fascia and subcutaneously, or to saline and intravenous ketorolac, Group C (Control, n = 28), in a double-blind study. Post-operative pain, analgesic consumption, side-effects, and home discharge were analysed. Median dose of rescue morphine given 0-24 h after surgery was significantly lower in group LIA (18 mg, IQR 5-25 mg) compared with group C (27 mg, IQR 15-43 mg, P = 0.028). Median time to first analgesic injection was significantly longer in group LIA (40 min, IQR 20-60 min) compared with group C (20 min, IQR 12-30 min, P = 0.009). NRS score was lower in the group LIA compared with group C in the direct post-operative period (0-2 h). No differences were found in post-operative side-effects or home discharge between the groups. Systematically injected local infiltration analgesia for pain management was superior to saline in the primary endpoint, resulting in significantly lower rescue morphine requirements during 0-24 h, longer time to first analgesic request and lower early post-operative pain intensity. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  13. Developing Open Source System Expertise in Europe

    DEFF Research Database (Denmark)

    Nyborg, Mads; Gustafsson, Finn; Christensen, Jørgen Erik

    2011-01-01

    programme (IP). The aim of this IP is to exchange knowledge of and experience in local methods and techniques in the field of open source software knowledge in ICT by engaging a group of international students and lecturers in a joint, explorative investigation of contemporary methods of open...... are interested in knowing which factors play a role in information systems and what the similarities and differences between the various national approaches in open source software systems and techniques are. The event forms a unique opportunity in promoting active learning in an international environment...... source software systems. In addition the program focuses on the students learning interpersonal skills, such as personal and professional skills, multidisciplinary teamwork, communication, communication in a foreign language and leadership. The target group consists of European engineering students who...

  14. The blood-brain barrier: structure, function and therapeutic approaches to cross it.

    Science.gov (United States)

    Tajes, Marta; Ramos-Fernández, Eva; Weng-Jiang, Xian; Bosch-Morató, Mònica; Guivernau, Biuse; Eraso-Pichot, Abel; Salvador, Bertrán; Fernàndez-Busquets, Xavier; Roquer, Jaume; Muñoz, Francisco J

    2014-08-01

    The blood-brain barrier (BBB) is constituted by a specialized vascular endothelium that interacts directly with astrocytes, neurons and pericytes. It protects the brain from the molecules of the systemic circulation but it has to be overcome for the proper treatment of brain cancer, psychiatric disorders or neurodegenerative diseases, which are dramatically increasing as the population ages. In the present work we have revised the current knowledge on the cellular structure of the BBB and the different procedures utilized currently and those proposed to cross it. Chemical modifications of the drugs, such as increasing their lipophilicity, turn them more prone to be internalized in the brain. Other mechanisms are the use of molecular tools to bind the drugs such as small immunoglobulins, liposomes or nanoparticles that will act as Trojan Horses favoring the drug delivery in brain. This fusion of the classical pharmacology with nanotechnology has opened a wide field to many different approaches with promising results to hypothesize that BBB will not be a major problem for the new generation of neuroactive drugs. The present review provides an overview of all state-of-the-art of the BBB structure and function, as well as of the classic strategies and these appeared in recent years to deliver drugs into the brain for the treatment of Central Nervous System (CNS) diseases.

  15. Market integration of local energy systems: Is local energy management compatible with European regulation for retail competition?

    NARCIS (Netherlands)

    Eid, C.; Bollinger, L.A.; Koirala, B.P.; Scholten, D.J.; Facchinetti, E.; Lilliestam, J.; Hakvoort, R.A.

    2016-01-01

    The growing penetration of distributed energy resources is opening up opportunities for local energy management (LEM) – the coordination of decentralized energy supply, storage, transport, conversion and consumption within a given geographical area. Because European electricity market liberalization

  16. openPSTD: The open source pseudospectral time-domain method for acoustic propagation

    Science.gov (United States)

    Hornikx, Maarten; Krijnen, Thomas; van Harten, Louis

    2016-06-01

    An open source implementation of the Fourier pseudospectral time-domain (PSTD) method for computing the propagation of sound is presented, which is geared towards applications in the built environment. Being a wave-based method, PSTD captures phenomena like diffraction, but maintains efficiency in processing time and memory usage as it allows to spatially sample close to the Nyquist criterion, thus keeping both the required spatial and temporal resolution coarse. In the implementation it has been opted to model the physical geometry as a composition of rectangular two-dimensional subdomains, hence initially restricting the implementation to orthogonal and two-dimensional situations. The strategy of using subdomains divides the problem domain into local subsets, which enables the simulation software to be built according to Object-Oriented Programming best practices and allows room for further computational parallelization. The software is built using the open source components, Blender, Numpy and Python, and has been published under an open source license itself as well. For accelerating the software, an option has been included to accelerate the calculations by a partial implementation of the code on the Graphical Processing Unit (GPU), which increases the throughput by up to fifteen times. The details of the implementation are reported, as well as the accuracy of the code.

  17. Delivery of chemotherapeutics across the blood-brain barrier: challenges and advances.

    Science.gov (United States)

    Doolittle, Nancy D; Muldoon, Leslie L; Culp, Aliana Y; Neuwelt, Edward A

    2014-01-01

    The blood-brain barrier (BBB) limits drug delivery to brain tumors. We utilize intraarterial infusion of hyperosmotic mannitol to reversibly open the BBB by shrinking endothelial cells and opening tight junctions between the cells. This approach transiently increases the delivery of chemotherapy, antibodies, and nanoparticles to brain. Our preclinical studies have optimized the BBB disruption (BBBD) technique and clinical studies have shown its safety and efficacy. The delivery of methotrexate-based chemotherapy in conjunction with BBBD provides excellent outcomes in primary central nervous system lymphoma (PCNSL) including stable or improved cognitive function in survivors a median of 12 years (range 2-26 years) after diagnosis. The addition of rituximab to chemotherapy with BBBD for PCNSL can be safely accomplished with excellent overall survival. Our translational studies of thiol agents to protect against platinum-induced toxicities led to the development of a two-compartment model in brain tumor patients. We showed that delayed high-dose sodium thiosulfate protects against carboplatin-induced hearing loss, providing the framework for large cooperative group trials of hearing chemoprotection. Neuroimaging studies have identified that ferumoxytol, an iron oxide nanoparticle blood pool agent, appears to be a superior contrast agent to accurately assess therapy-induced changes in brain tumor vasculature, in brain tumor response to therapy, and in differentiating central nervous system lesions with inflammatory components. This chapter reviews the breakthroughs, challenges, and future directions for BBBD. © 2014 Elsevier Inc. All rights reserved.

  18. Delivery of Chemotherapeutics Across the Blood–Brain Barrier: Challenges and Advances

    Science.gov (United States)

    Doolittle, Nancy D.; Muldoon, Leslie L.; Culp, Aliana Y.; Neuwelt, Edward A.

    2017-01-01

    The blood–brain barrier (BBB) limits drug delivery to brain tumors. We utilize intraarterial infusion of hyperosmotic mannitol to reversibly open the BBB by shrinking endothelial cells and opening tight junctions between the cells. This approach transiently increases the delivery of chemotherapy, antibodies, and nanoparticles to brain. Our preclinical studies have optimized the BBB disruption (BBBD) technique and clinical studies have shown its safety and efficacy. The delivery of methotrexate-based chemotherapy in conjunction with BBBD provides excellent outcomes in primary central nervous system lymphoma (PCNSL) including stable or improved cognitive function in survivors a median of 12 years (range 2–26 years) after diagnosis. The addition of rituximab to chemotherapy with BBBD for PCNSL can be safely accomplished with excellent overall survival. Our translational studies of thiol agents to protect against platinum-induced toxicities led to the development of a two-compartment model in brain tumor patients. We showed that delayed high-dose sodium thiosulfate protects against carboplatin-induced hearing loss, providing the framework for large cooperative group trials of hearing chemoprotection. Neuroimaging studies have identified that ferumoxytol, an iron oxide nanoparticle blood pool agent, appears to be a superior contrast agent to accurately assess therapy-induced changes in brain tumor vasculature, in brain tumor response to therapy, and in differentiating central nervous system lesions with inflammatory components. This chapter reviews the breakthroughs, challenges, and future directions for BBBD. PMID:25307218

  19. Jumping Hurdles: Peptides Able To Overcome Biological Barriers.

    Science.gov (United States)

    Sánchez-Navarro, Macarena; Teixidó, Meritxell; Giralt, Ernest

    2017-08-15

    The cell membrane, the gastrointestinal tract, and the blood-brain barrier (BBB) are good examples of biological barriers that define and protect cells and organs. They impose different levels of restriction, but they also share common features. For instance, they all display a high lipophilic character. For this reason, hydrophilic compounds, like peptides, proteins, or nucleic acids have long been considered as unable to bypass them. However, the discovery of cell-penetrating peptides (CPPs) opened a vast field of research. Nowadays, CPPs, homing peptides, and blood-brain barrier peptide shuttles (BBB-shuttles) are good examples of peptides able to target and to cross various biological barriers. CPPs are a group of peptides able to interact with the plasma membrane and enter the cell. They display some common characteristics like positively charged residues, mainly arginines, and amphipathicity. In this field, our group has been focused on the development of proline rich CPPs and in the analysis of the importance of secondary amphipathicity in the internalization process. Proline has a privileged structure being the only amino acid with a secondary amine and a cyclic side chain. These features constrain its structure and hamper the formation of H-bonds. Taking advantage of this privileged structure, three different families of proline-rich peptides have been developed, namely, a proline-rich dendrimer, the sweet arrow peptide (SAP), and a group of foldamers based on γ-peptides. The structure and the mechanism of internalization of all of them has been evaluated and analyzed. BBB-shuttles are peptides able to cross the BBB and to carry with them compounds that cannot reach the brain parenchyma unaided. These peptides take advantage of the natural transport mechanisms present at the BBB, which are divided in active and passive transport mechanisms. On the one hand, we have developed BBB-shuttles that cross the BBB by a passive transport mechanism, like

  20. OSGeo - Open Source Geospatial Foundation

    Directory of Open Access Journals (Sweden)

    Margherita Di Leo

    2012-09-01

    Full Text Available L'esigenza nata verso la fine del 2005 di selezionare ed organizzare più di 200 progetti FOSS4G porta alla nascita nel Febbraio2006 di OSGeo (the Open Source Geospatial Foundation, organizzazione internazionale la cui mission è promuovere lo sviluppo collaborativo di software libero focalizzato sull'informazione geografica (FOSS4G.Open   Source   Geospatial   Foundation (OSGeoThe Open Source Geospatial Foundation (OSGeo  is  a  not-for-profit  organization, created  in  early  2006  to  the  aim  at  sup-porting   the   collaborative   development of  geospatial  open  source  software,  and promote its widespread use. The founda-tion provides financial, organizational and legal support to the broader open source geospatial community. It also serves as an independent  legal  entity  to  which  com-munity  members  can  contribute  code, funding  and  other  resources,  secure  in the knowledge that their contributions will be maintained for public benefit. OSGeo also  serves  as  an  outreach  and  advocacy organization for the open source geospa-tial  community,  and  provides  a  common forum  and  shared  infrastructure  for  im-proving  cross-project  collaboration.  The foundation's projects are all freely available and  useable  under  an  OSI-certified  open source license. The Italian OSGeo local chapter is named GFOSS.it     (Associazione     Italiana     per l'informazione Geografica Libera.

  1. Entanglement in open quantum systems

    International Nuclear Information System (INIS)

    Isar, A.

    2007-01-01

    In the framework of the theory of open systems based on quantum dynamical semigroups, we solve the master equation for two independent bosonic oscillators interacting with an environment in the asymptotic long-time regime. We give a description of the continuous-variable entanglement in terms of the covariance matrix of the quantum states of the considered system for an arbitrary Gaussian input state. Using the Peres-Simon necessary and sufficient condition for separability of two-mode Gaussian states, we show that the two non-interacting systems immersed in a common environment and evolving under a Markovian, completely positive dynamics become asymptotically entangled for certain environments, so that their non-local quantum correlations exist in the long-time regime. (author) Key words: quantum information theory, open systems, quantum entanglement, inseparable states

  2. Open Educational Resources: American Ideals, Global Questions

    Science.gov (United States)

    Weiland, Steven

    2015-01-01

    Educational relations between societies and cultures that begin with benevolent intentions can come to be seen as threats to national autonomy and local preferences. Indeed, side by side with the growth since the first years of this century of Open Educational Resources (OER) there has been worry about their impact on global educational…

  3. Hack The Government! Empowering Citizens to Make Meaningful Use of Open Data

    DEFF Research Database (Denmark)

    Molinari, Francesco; Concilio, Grazia; Mulder, Ingrid

    2016-01-01

    Citizens’ use of Open Data is often limited to the use of apps. The design of the (app based) public service as well as the interpretation of the data is done for them. The organization of local hackathons can promote citizens’ data literacy and better use of available Open Data for service...

  4. Land & Development in Latin America: Issues and Openings for ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... openings and constraints with regard to such policies at the local, national, and international levels? ... land policy initiatives in areas like titling, credit, taxation, and sustainable land use; and ... ROSSA's latest bulletin puts a focus on women.

  5. Consistent boundary conditions for open strings

    International Nuclear Information System (INIS)

    Lindstroem, Ulf; Rocek, Martin; Nieuwenhuizen, Peter van

    2003-01-01

    We study boundary conditions for the bosonic, spinning (NSR) and Green-Schwarz open string, as well as for (1+1)-dimensional supergravity. We consider boundary conditions that arise from (1) extremizing the action, (2) BRST, rigid or local supersymmetry, or κ(Siegel)-symmetry of the action, (3) closure of the set of boundary conditions under the symmetry transformations, and (4) the boundary limits of bulk Euler-Lagrange equations that are 'conjugate' to other boundary conditions. We find corrections to Neumann boundary conditions in the presence of a bulk tachyon field. We discuss a boundary superspace formalism. We also find that path integral quantization of the open string requires an infinite tower of boundary conditions that can be interpreted as a smoothness condition on the doubled interval; we interpret this to mean that for a path-integral formulation of open strings with only Neuman boundary conditions, the description in terms of orientifolds is not just natural, but is actually fundamental

  6. openQ*D simulation code for QCD+QED

    Science.gov (United States)

    Campos, Isabel; Fritzsch, Patrick; Hansen, Martin; Krstić Marinković, Marina; Patella, Agostino; Ramos, Alberto; Tantalo, Nazario

    2018-03-01

    The openQ*D code for the simulation of QCD+QED with C* boundary conditions is presented. This code is based on openQCD-1.6, from which it inherits the core features that ensure its efficiency: the locally-deflated SAP-preconditioned GCR solver, the twisted-mass frequency splitting of the fermion action, the multilevel integrator, the 4th order OMF integrator, the SSE/AVX intrinsics, etc. The photon field is treated as fully dynamical and C* boundary conditions can be chosen in the spatial directions. We discuss the main features of openQ*D, and we show basic test results and performance analysis. An alpha version of this code is publicly available and can be downloaded from http://rcstar.web.cern.ch/.

  7. Targeted, noninvasive blockade of cortical neuronal activity

    Science.gov (United States)

    McDannold, Nathan; Zhang, Yongzhi; Power, Chanikarn; Arvanitis, Costas D.; Vykhodtseva, Natalia; Livingstone, Margaret

    2015-11-01

    Here we describe a novel method to noninvasively modulate targeted brain areas through the temporary disruption of the blood-brain barrier (BBB) via focused ultrasound, enabling focal delivery of a neuroactive substance. Ultrasound was used to locally disrupt the BBB in rat somatosensory cortex, and intravenous administration of GABA then produced a dose-dependent suppression of somatosensory-evoked potentials in response to electrical stimulation of the sciatic nerve. No suppression was observed 1-5 days afterwards or in control animals where the BBB was not disrupted. This method has several advantages over existing techniques: it is noninvasive; it is repeatable via additional GABA injections; multiple brain regions can be affected simultaneously; suppression magnitude can be titrated by GABA dose; and the method can be used with freely behaving subjects. We anticipate that the application of neuroactive substances in this way will be a useful tool for noninvasively mapping brain function, and potentially for surgical planning or novel therapies.

  8. Nuclear shielding of openings in ITER Tokamak building

    Energy Technology Data Exchange (ETDEWEB)

    Dammann, A., E-mail: alexis.dammann@iter.org [ITER Organization, Route de Vinon sur Verdon, 13115 Saint Paul Lez Durance (France); Arumugam, A.P.; Beaudoin, V.; Beltran, D.; Benchikhoune, M.; Berruyer, F.; Cortes, P.; Gandini, F. [ITER Organization, Route de Vinon sur Verdon, 13115 Saint Paul Lez Durance (France); Ghirelli, N. [ASSYSTEM E.O.S, ZAC Saint Martin, 23, rue Benjamin Franklin, 84120 Pertuis (France); Gray, A.; Hurzlmeier, H.; Le Page, M. [ITER Organization, Route de Vinon sur Verdon, 13115 Saint Paul Lez Durance (France); Lemée, A. [SOGETI High Tech, 180 Rue René Descartes, 13851 Aix en Provence (France); Lentini, G.; Loughlin, M.; Mita, Y.; Patisson, L.; Rigoni, G.; Rathi, D.; Song, I. [ITER Organization, Route de Vinon sur Verdon, 13115 Saint Paul Lez Durance (France)

    2013-10-15

    Highlights: ► Establishment of a methodology to design shielded opening in external wall of the Tokamak building. ► Analysis of the shielding requirement, case by case, depending on the localization and the context. ► Implementation of an integrated solution for shielded opening. -- Abstract: The external walls of the Tokamak building, made of thick concrete, provide the nuclear shielding for operators working in adjacent buildings and for the environment. There are a series of openings to these external walls, devoted to ducts or pipes for ventilation, waveguides and transmission lines for heating systems and diagnostics, cooling pipes, cable trays or busbars. The shielding properties of the wall shall be preserved by adequate design of the openings in order not to affect the radiological zoning in adjacent areas. For some of them, shielding properties of the wall are not affected because the size of the network is quite small or the source is far from the opening. But for most of the openings, specific features shall be considered. Even if the approach is the same and the ways to shield can be standardized, specific analysis is requested in any case because the constraints are different.

  9. Open life science research, open software and the open century

    Directory of Open Access Journals (Sweden)

    Youhua Chen

    2015-05-01

    Full Text Available At the age of knowledge explosion and mass scientific information, I highlighted the importance of conducting open science in life and medical researches through the extensive usage of open software and documents. The proposal of conducting open science is to reduce the limited repeatability of researches in life science. I outlined the essential steps for conducting open life science and the necessary standards for creating, reusing and reproducing open materials. Different Creative Commons licenses were presented and compared of their usage scope and restriction. As a conclusion, I argued that open materials should be widely adopted in doing life and medical researches.

  10. Analisis Kinerja Local Area Network Menggunakan Router.

    OpenAIRE

    Hutahaean, Yosua

    2012-01-01

    Perangkat internetworking menawarkan komunikasi di antara segmen Local Area Network (LAN). Ada empat tipe utama perangkat internetworking ini: repeater, bridge, router, dan gateway. Perangkat ini dibedakan atas dasar system lapisan Open System Interconnection (OSI) yang digunakan, berfungsi sebagai media komunikasi dari LAN ke LAN. Pada Tugas Akhir ini penulis tertarik untuk membahas analisis kinerja Local Area Network (LAN) menggunakan Router yang menggunakan sistem antrian M/M/1 dimana j...

  11. Assessment of crack opening area for leak rates

    International Nuclear Information System (INIS)

    Sharples, J.K.; Bouchard, P.J.

    1997-01-01

    This paper outlines the background to recommended crack opening area solutions given in a proposed revision to leak before break guidance for the R6 procedure. Comparisons with experimental and analytical results are given for some selected cases of circumferential cracks in cylinders. It is shown that elastic models can provide satisfactory estimations of crack opening displacement (and area) but they become increasingly conservative for values of L r greater than approximately 0.4. The Dugdale small scale yielding model gives conservative estimates of crack opening displacement with increasing enhancement for L r values greater than 0.4. Further validation of the elastic-plastic reference stress method for up to L r values of about 1.0 is presented by experimental and analytical comparisons. Although a more detailed method, its application gives a best estimate of crack opening displacement which may be substantially greater than small scale plasticity models. It is also shown that the local boundary conditions in pipework need to be carefully considered when evaluating crack opening area for through-wall bending stresses resulting from welding residual stresses or geometry discontinuities

  12. Rapid and efficient localization of depth electrodes and cortical labeling using free and open source medical software in epilepsy surgery candidates

    Directory of Open Access Journals (Sweden)

    Juan Pablo Princich

    2013-12-01

    Full Text Available Depth intracranial electrodes (IEs placement is one of the most used procedures to identify the epileptogenic zone (EZ in surgical treatment of drug resistant epilepsy patients, about 20-30% of this population. IEs localization is therefore a critical issue defining the EZ and its relation with eloquent functional areas. That information is then used to target the resective surgery and has great potential to affect outcome.We designed a methodological procedure intended to avoid the need for highly specialized medical resources and reduce time to identify the anatomical location of IEs, during the first instances of intracranial EEG recordings. This workflow is based on established open source software; 3D Slicer and Freesurfer that uses MRI and Post-implant CT fusion for the localization of IEs and its relation with automatic labeled surrounding cortex. To test this hypothesis we assessed the time elapsed between the surgical implantation process and the final anatomical localization of IEs by means of our proposed method compared against traditional visual analysis of raw post-implant imaging in two groups of patients.All IEs were identified in the first 24 Hs (6-24 Hs of implantation using our method in 4 patients of the first group. For the control group; all IEs were identified by experts with an overall time range of 36 h to 3 days using traditional visual analysis. It included (7 patients, 3 patients implanted with IEs and the same 4 patients from the first group. Time to localization was restrained in this group by the specialized personnel and the image quality available.To validate our method; we trained two inexperienced operators to assess the position of IEs contacts on four patients (5 intracranial electrodes using the proposed method. We quantified the discrepancies between operators and we also assessed the efficiency of our method to define the EZ comparing the findings against the results of traditional analysis.

  13. Weak openness and almost openness

    Directory of Open Access Journals (Sweden)

    David A. Rose

    1984-01-01

    Full Text Available Weak openness and almost openness for arbitrary functions between topological spaces are defined as duals to the weak continuity of Levine and the almost continuity of Husain respectively. Independence of these two openness conditions is noted and comparison is made between these and the almost openness of Singal and Singal. Some results dual to those known for weak continuity and almost continuity are obtained. Nearly almost openness is defined and used to obtain an improved link from weak continuity to almost continuity.

  14. NEMESIS : A Multigigabit Optical Local Area Network

    OpenAIRE

    Popescu, Adrian; Akyildizapo, Ian

    1994-01-01

    A new architecture is developed for an integrated 20 Gbps fiber optic Local Area Network (LAN) that supports data rates up to 9.6 Gbps. The architecture does not follow the standard, vertically-oriented Open System Interconnection (OSI) layering approach of other LANs. Instead, a horizontally-oriented model is introduced for the communication process to open up the three fundamental bottlenecks, i.e., opto-electronic, service and processing bottlenecks, that occur in a multi-Gbps integrated c...

  15. The Rural Open Air Museums: Visitors, Community and Place

    Directory of Open Access Journals (Sweden)

    Pawlikowska-Piechotka Anna

    2015-12-01

    Full Text Available Contemporary rural museums perform not only the traditional tasks but are also the places where both the visitors and the local community members have chances for entertainment and attractive leisure time. Consequently one can find in museums numerous catering offers such as cafes, bistros, snack bars, restaurants, pubs and wine bars. The material presented is the result of theoretical and field studies carried out in the selected open air museums in Poland and focused on newly introduced commercial activities (as catering. Our research results show that the development of sustainable cultural tourism as a generator of income in the open air rural museums is important in the challenging economic time. Museums having catering services of different character could easier overcome financial struggle. Moreover there is no doubt that the introduction of an interesting and ambitious cuisine in the restaurants located in the rural open air museum is of great importance also in other terms: popularization of the food culture, rural tradition of region, healthy diet and lifestyle, chance to increase the museum attractiveness, important economic support to the museum and the local community and the improvement of living quality.

  16. Local Heat Application for the Treatment of Buruli Ulcer: Results of a Phase II Open Label Single Center Non Comparative Clinical Trial.

    Science.gov (United States)

    Vogel, Moritz; Bayi, Pierre F; Ruf, Marie-Thérèse; Bratschi, Martin W; Bolz, Miriam; Um Boock, Alphonse; Zwahlen, Marcel; Pluschke, Gerd; Junghanss, Thomas

    2016-02-01

    Buruli ulcer (BU) is a necrotizing skin disease most prevalent among West African children. The causative organism, Mycobacterium ulcerans, is sensitive to temperatures above 37°C. We investigated the safety and efficacy of a local heat application device based on phase change material. In a phase II open label single center noncomparative clinical trial (ISRCTN 72102977) under GCP standards in Cameroon, laboratory confirmed BU patients received up to 8 weeks of heat treatment. We assessed efficacy based on the endpoints 'absence of clinical BU specific features' or 'wound closure' within 6 months ("primary cure"), and 'absence of clinical recurrence within 24 month' ("definite cure"). Of 53 patients 51 (96%) had ulcerative disease. 62% were classified as World Health Organization category II, 19% each as category I and III. The average lesion size was 45 cm(2). Within 6 months after completion of heat treatment 92.4% (49 of 53, 95% confidence interval [CI], 81.8% to 98.0%) achieved cure of their primary lesion. At 24 months follow-up 83.7% (41 of 49, 95% CI, 70.3% to 92.7%) of patients with primary cure remained free of recurrence. Heat treatment was well tolerated; adverse effects were occasional mild local skin reactions. Local thermotherapy is a highly effective, simple, cheap and safe treatment for M. ulcerans disease. It has in particular potential as home-based remedy for BU suspicious lesions at community level where laboratory confirmation is not available. ISRCT 72102977. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  17. Open Education and the Open Science Economy

    Science.gov (United States)

    Peters, Michael A.

    2009-01-01

    Openness as a complex code word for a variety of digital trends and movements has emerged as an alternative mode of "social production" based on the growing and overlapping complexities of open source, open access, open archiving, open publishing, and open science. This paper argues that the openness movement with its reinforcing structure of…

  18. Implementing an Open Source Learning Management System: A Critical Analysis of Change Strategies

    Science.gov (United States)

    Uys, Philip M.

    2010-01-01

    This paper analyses the change and innovation strategies that Charles Sturt University (CSU) used from 2007 to 2009 during the implementation and mainstreaming of an open source learning management system (LMS), Sakai, named locally as "CSU Interact". CSU was in January 2008 the first Australian University to implement an open source…

  19. Accelerating Translational Research through Open Science: The Neuro Experiment.

    Science.gov (United States)

    Gold, E Richard

    2016-12-01

    Translational research is often afflicted by a fundamental problem: a limited understanding of disease mechanisms prevents effective targeting of new treatments. Seeking to accelerate research advances and reimagine its role in the community, the Montreal Neurological Institute (Neuro) announced in the spring of 2016 that it is launching a five-year experiment during which it will adopt Open Science-open data, open materials, and no patenting-across the institution. The experiment seeks to examine two hypotheses. The first is whether the Neuro's Open Science initiative will attract new private partners. The second hypothesis is that the Neuro's institution-based approach will draw companies to the Montreal region, where the Neuro is based, leading to the creation of a local knowledge hub. This article explores why these hypotheses are likely to be true and describes the Neuro's approach to exploring them.

  20. Accelerating Translational Research through Open Science: The Neuro Experiment.

    Directory of Open Access Journals (Sweden)

    E Richard Gold

    2016-12-01

    Full Text Available Translational research is often afflicted by a fundamental problem: a limited understanding of disease mechanisms prevents effective targeting of new treatments. Seeking to accelerate research advances and reimagine its role in the community, the Montreal Neurological Institute (Neuro announced in the spring of 2016 that it is launching a five-year experiment during which it will adopt Open Science-open data, open materials, and no patenting-across the institution. The experiment seeks to examine two hypotheses. The first is whether the Neuro's Open Science initiative will attract new private partners. The second hypothesis is that the Neuro's institution-based approach will draw companies to the Montreal region, where the Neuro is based, leading to the creation of a local knowledge hub. This article explores why these hypotheses are likely to be true and describes the Neuro's approach to exploring them.

  1. Towards an Open Modelling Interface (OpenMI the HarmonIT project

    Directory of Open Access Journals (Sweden)

    M. Blind

    2005-01-01

    Full Text Available The Water Framework Directive (WFD poses an immense challenge to water management in Europe. Aiming at a "good ecological status" of surface waters in 2015, integrated river basin management plans need to be in place by 2009, and broadly supported by stakeholders. Information & Communication Technology (ICT tools, such as computational models, are very helpful in designing river basin management plans (rbmp-s. However, many scientists believe that a single integrated modelling system to support the WFD cannot be developed, and integrated systems need to be quite tailored to the local situation and evolve during a collaborative planning process. As a consequence there is an urgent need to increase the flexibility of modelling systems, such that dedicated model systems can be developed from available building blocks. In the recent past a number of initiatives have been started to develop an IT framework for modelling to meet the required flexibility. In Europe the international project HarmonIT, which is sponsored by the European Commission, is developing and implementing a standard interface for modelling components and other relevant tools: The Open Modelling Interface (OpenMI. This paper describes the HarmonIT project and objectives in general. The current progress is described. It describes the roles for different types of stakeholders in modelling, varying from software coders to non-specialized users of decision support systems. It will provide insight in the requirements imposed when using the OpenMI.

  2. A Design-Adaptive Local Polynomial Estimator for the Errors-in-Variables Problem

    KAUST Repository

    Delaigle, Aurore

    2009-03-01

    Local polynomial estimators are popular techniques for nonparametric regression estimation and have received great attention in the literature. Their simplest version, the local constant estimator, can be easily extended to the errors-in-variables context by exploiting its similarity with the deconvolution kernel density estimator. The generalization of the higher order versions of the estimator, however, is not straightforward and has remained an open problem for the last 15 years. We propose an innovative local polynomial estimator of any order in the errors-in-variables context, derive its design-adaptive asymptotic properties and study its finite sample performance on simulated examples. We provide not only a solution to a long-standing open problem, but also provide methodological contributions to error-invariable regression, including local polynomial estimation of derivative functions.

  3. Global forces and local currents in Argentina's science policy crossroads: restricted access or open knowledge

    Directory of Open Access Journals (Sweden)

    Horacio Javier Etchichury

    2014-11-01

    Full Text Available The article describes the tensions between two competing approaches to scientific policy in Argentina. The traditional vision favors autonomous research. The neoliberal conception fosters the link between science and markets. In the past few years, a neodevelopmentalist current also tries to stress relevance of scientific research. Finally, the article describes how the Open Access movement has entered the debate. The World Bank intervention and the human rights dimension of the question are discussed in depth. The article introduces the notion of open knowledge as a guiding criterion to design a human-rights based scientific policy.

  4. Use of the Paid Open Access Option in Hybrid Open Access Journals in Agriculture: A Mixed-Methods Study

    Directory of Open Access Journals (Sweden)

    Megan Kocher

    2016-12-01

    Full Text Available We explore the use and usefulness of the hybrid open access publishing model in agricultural sciences using a combination of quantitative and qualitative methods. To ascertain the level of usage of the paid open access option in hybrid open access journals in agriculture, we studied the agriculture-related journals published by six commercial publishers. These publishers offer authors the option of paying a fee, often close to $3,000 per article, to make their article immediately freely available, usually with a Creative Commons license. We defined agriculture broadly but also assigned each journal to a subspecialty (e.g., animal science in order to see if there were differences based on these subdivisions. For each journal we gathered data for 2014-2015 and noted the total number of research articles and the number of those that were made freely available by authors paying the open access fee. To give context to our results we also surveyed local faculty in agricultural sciences, asking their reasons for considering the paid open access options and the sources of the funds to pay for it. Survey respondents were asked about their academic position and rank to see if there were differences to be noted. We also investigated the findability of the open access articles, noting if each individual publisher offered a way to easily locate all the freely available articles in a particular journal and if there are other avenues to easily locate these articles.

  5. Facilitating Full-text Access to Biomedical Literature Using Open Access Resources.

    Science.gov (United States)

    Kang, Hongyu; Hou, Zhen; Li, Jiao

    2015-01-01

    Open access (OA) resources and local libraries often have their own literature databases, especially in the field of biomedicine. We have developed a method of linking a local library to a biomedical OA resource facilitating researchers' full-text article access. The method uses a model based on vector space to measure similarities between two articles in local library and OA resources. The method achieved an F-score of 99.61%. This method of article linkage and mapping between local library and OA resources is available for use. Through this work, we have improved the full-text access of the biomedical OA resources.

  6. Bundle branch block after ablation for Wolff-Parkinson-White syndrome.

    Science.gov (United States)

    Fuenmayor A, Abdel J; Rodríguez S, Yenny A

    2013-09-20

    Bundle branch block (BBB) is a difficult diagnosis in the Wolff-Parkinson-White syndrome (WPW). We investigated the clinical implications of BBB that appears after performing an accessory pathway (AP) ablation. We studied 199 patients with WPW who were submitted to AP ablation. Thirty (15%) exhibited BBB after the ablation. Twenty-two patients had right BBB and 8 had left BBB. Thirteen patients had right-sided AP and 17 had left-sided AP. They were compared with 82 similar patients without BBB after the AP ablation. Among the patients with BBB, 86.66% showed delays in the middle part of the QRS in the ECG recorded before ablation vs. 18.29% of the patients without BBB (p<0.05) (sensitivity 86%, specificity 81%, positive predictive value 67% and negative predictive value 93%). Forty-four percent of the patients with BBB had BBB morphology during orthodromic tachycardia vs. 10% of the patients without BBB (p<0.05) (sensitivity 44%, specificity 89%, positive predictive value 57% and negative predictive value 82%). No relationship was found between AP location and the site of the BBB. Ejection fraction was normal before (0.61 ± 0.03) and upon completion of follow-up (0.61 ± 0.07). BBB disappeared in 95.3% of the patients. Delays in the middle portion of the QRS may predict BBB after AP ablation. BBB after performing AP ablation is frequent, transient, benign, and not related to either the ablation lesion location or progression to structural heart disease. BBB after AP ablation may be related to cardiac memory. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. Critical appraisal of outcomes following open radical prostatectomy.

    Science.gov (United States)

    Galvin, David J; Eastham, James A

    2009-05-01

    Radical prostatectomy has evolved enormously over the last 25 years. Improvements include the use of smaller incisions, reduced blood loss, shorter hospital stays, and surgical refinement to improve the recovery of continence and potency. In addition, new technologies and minimally invasive techniques with the potential to further improve patient outcomes have been introduced. This article focuses on outcomes with open radical prostatectomy and is not meant to compare open radical prostatectomy and minimally invasive approaches. Despite a lack of randomized controlled trials, strong observational cohort studies demonstrate lower rates of positive surgical margins, high 10-year and 15-year biochemical recurrence-free rates, excellent prostate cancer-specific mortality rates, and improved recovery of urinary incontinence and erectile function after open radical prostatectomy. We review publications from the past 24 months regarding oncologic outcome, continence, and erectile function, as well as some earlier manuscripts that emphasize key aspects of open radical prostatectomy. Today open radical prostatectomy is a less-invasive procedure with low morbidity providing excellent control of clinically localized prostate cancer. Although open radical prostatectomy now accounts for a minority of radical prostatectomies in the United States, the concepts that have improved oncologic and quality-of-life outcomes are equally applicable to minimally invasive procedures.

  8. The Brainomics/Localizer database.

    Science.gov (United States)

    Papadopoulos Orfanos, Dimitri; Michel, Vincent; Schwartz, Yannick; Pinel, Philippe; Moreno, Antonio; Le Bihan, Denis; Frouin, Vincent

    2017-01-01

    The Brainomics/Localizer database exposes part of the data collected by the in-house Localizer project, which planned to acquire four types of data from volunteer research subjects: anatomical MRI scans, functional MRI data, behavioral and demographic data, and DNA sampling. Over the years, this local project has been collecting such data from hundreds of subjects. We had selected 94 of these subjects for their complete datasets, including all four types of data, as the basis for a prior publication; the Brainomics/Localizer database publishes the data associated with these 94 subjects. Since regulatory rules prevent us from making genetic data available for download, the database serves only anatomical MRI scans, functional MRI data, behavioral and demographic data. To publish this set of heterogeneous data, we use dedicated software based on the open-source CubicWeb semantic web framework. Through genericity in the data model and flexibility in the display of data (web pages, CSV, JSON, XML), CubicWeb helps us expose these complex datasets in original and efficient ways. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Assessment of crack opening area for leak rates

    Energy Technology Data Exchange (ETDEWEB)

    Sharples, J.K.; Bouchard, P.J.

    1997-04-01

    This paper outlines the background to recommended crack opening area solutions given in a proposed revision to leak before break guidance for the R6 procedure. Comparisons with experimental and analytical results are given for some selected cases of circumferential cracks in cylinders. It is shown that elastic models can provide satisfactory estimations of crack opening displacement (and area) but they become increasingly conservative for values of L{sub r} greater than approximately 0.4. The Dugdale small scale yielding model gives conservative estimates of crack opening displacement with increasing enhancement for L{sub r} values greater than 0.4. Further validation of the elastic-plastic reference stress method for up to L{sub r} values of about 1.0 is presented by experimental and analytical comparisons. Although a more detailed method, its application gives a best estimate of crack opening displacement which may be substantially greater than small scale plasticity models. It is also shown that the local boundary conditions in pipework need to be carefully considered when evaluating crack opening area for through-wall bending stresses resulting from welding residual stresses or geometry discontinuities.

  10. Open hardware for open science

    CERN Multimedia

    CERN Bulletin

    2011-01-01

    Inspired by the open source software movement, the Open Hardware Repository was created to enable hardware developers to share the results of their R&D activities. The recently published CERN Open Hardware Licence offers the legal framework to support this knowledge and technology exchange.   Two years ago, a group of electronics designers led by Javier Serrano, a CERN engineer, working in experimental physics laboratories created the Open Hardware Repository (OHR). This project was initiated in order to facilitate the exchange of hardware designs across the community in line with the ideals of “open science”. The main objectives include avoiding duplication of effort by sharing results across different teams that might be working on the same need. “For hardware developers, the advantages of open hardware are numerous. For example, it is a great learning tool for technologies some developers would not otherwise master, and it avoids unnecessary work if someone ha...

  11. Treatment of Unicameral Bone Cysts: A Comparison on the Use of Steroid Injectionand Open Surgery

    Directory of Open Access Journals (Sweden)

    Celil Alemdar

    2014-03-01

    Full Text Available Aim: In this study we compared the clinical outcomes of the patients who underwent steroid injection and the ones who received additional local adjuvant therapy (cauterization alcohol following open surgery. Material and Method: The retrospective study included 73 patients who were diagnosed with unicameral bone cyst and underwent steroid injection or open surgery between 1995 and 2011. The patients comprised 23 (31.5% females and 50 (68.5% males, with a mean age of 9 (6-18 years and mean follow-up period of 4.71 (2-9 years. Open surgery was performed in 49 and steroid injection in 24 patients. In the open surgery group, local adjuvant treatment was added subsequently. In this group, healing was viewed radiologically. The patients were analyzed in three groups depending on the rate of the filling of the cystic area with a new bone: (I complete healing, (II residual healing, and (III inadequate healing. Results: In the steroid injection group, complete healing was observed in 5 (20.8%, residual healing in 13 (54.1%, and complete failure in 6 (25% patients. Average healing time was 32 (13-45 months. In the open surgery group, complete healing occurred in 24 (48.9%, residual healing in 20 (40.8%, and complete failure in 5 (10.2% patients. Average healing time was 15 (10-29 months. Discussion: Steroid Injection is a practical and minimally-invasive method, yet it leads to a lower success rate when compared to open surgery combined with local adjuvant therapy.

  12. Interface Between Research, Development and Local Actors in ...

    African Journals Online (AJOL)

    Interface Between Research, Development and Local Actors in Enhancing ... Open Access DOWNLOAD FULL TEXT ... Environmental sustainability is a key area of focus in academic and development circles mainly because of the role that the ...

  13. Dimensional enrichment of statistical linked open data

    DEFF Research Database (Denmark)

    Varga, Jovan; Vaisman, Alejandro; Romero, Oscar

    2016-01-01

    On-Line Analytical Processing (OLAP) is a data analysis technique typically used for local and well-prepared data. However, initiatives like Open Data and Open Government bring new and publicly available data on the web that are to be analyzed in the same way. The use of semantic web technologies...... for this context is especially encouraged by the Linked Data initiative. There is already a considerable amount of statistical linked open data sets published using the RDF Data Cube Vocabulary (QB) which is designed for these purposes. However, QB lacks some essential schema constructs (e.g., dimension levels......) to support OLAP. Thus, the QB4OLAP vocabulary has been proposed to extend QB with the necessary constructs and be fully compliant with OLAP. In this paper, we focus on the enrichment of an existing QB data set with QB4OLAP semantics. We first thoroughly compare the two vocabularies and outline the benefits...

  14. Open access, open education resources and open data in Uganda.

    Science.gov (United States)

    Salvo, Ivana Di; Mwoka, Meggie; Kwaga, Teddy; Rukundo, Priscilla Aceng; Ernest, Dennis Ssesanga; Osaheni, Louis Aikoriogie; John, Kasibante; Shafik, Kasirye; de Sousa, Agostinho Moreira

    2015-01-01

    As a follow up to OpenCon 2014, International Federation of Medical Students' Associations (IFMSA) students organized a 3 day workshop Open Access, Open Education Resources and Open Data in Kampala from 15-18 December 2014. One of the aims of the workshop was to engage the Open Access movement in Uganda which encompasses the scientific community, librarians, academia, researchers and students. The IFMSA students held the workshop with the support of: Consortium for Uganda University Libraries (CUUL), The Right to Research Coalition, Electronic Information for Libraries (EIFL), Makerere University, International Health Sciences University (IHSU), Pan African Medical Journal (PAMJ) and the Centre for Health Human Rights and Development (CEHURD). All these organizations are based or have offices in Kampala. The event culminated in a meeting with the Science and Technology Committee of Parliament of Uganda in order to receive the support of the Ugandan Members of Parliament and to make a concrete change for Open Access in the country.

  15. Interaction between Cities and Climate Change: Modelling Urban Morphology and Local Urban Planning Scenarios from Open Datasets across European Cities

    Science.gov (United States)

    Thomas, Bart; Stevens, Catherine; Grommen, Mart

    2015-04-01

    Cities are characterised by a large spatiotemporal diversity of local climates induced by a superposition of various factors and processes interacting at global and regional scales but also at the micro level such as the urban heat island effect. As urban areas are known as 'hot spots' prone to climate and its variability over time leading to changes in the severity and occurrence of extreme events such as heat waves, it is of crucial importance to capture the spatial heterogeneity resulting from variations in land use land cover (LULC) and urban morphology in an effective way to drive local urban climate simulations. The first part of the study conducted in the framework of the NACLIM FP7 project funded by the European Commission focusses on the extraction of land surface parameters linked to urban morphology characteristics from detailed 3D city models and their relationship with openly accessible European datasets such as the degree of soil sealing and disaggregated population densities from the European Environment Agency (EEA) and the Joint Research Centre (JRC). While it has been demonstrated that good correlations can be found between those datasets and the planar and frontal area indices, the present work has expanded the research to other urban morphology parameters including the average and variation of the building height and the sky view factor. Correlations up to 80% have been achieved depending on the considered parameter and the specific urban area including the cities of Antwerp (Belgium), Berlin (Germany) and Almada (Portugal) represented by different climate and urban characteristics. Moreover, the transferability of the established relations has been investigated across the various cities. Secondly, a flexible and scalable approach as a function of the required the level of detail has been elaborated to update the various morphology parameters in case of integration with urban planning data to analyse the local impact of future land use scenarios

  16. Open Content in Open Context

    Science.gov (United States)

    Kansa, Sarah Whitcher; Kansa, Eric C.

    2007-01-01

    This article presents the challenges and rewards of sharing research content through a discussion of Open Context, a new open access data publication system for field sciences and museum collections. Open Context is the first data repository of its kind, allowing self-publication of research data, community commentary through tagging, and clear…

  17. Openness, Web 2.0 Technology, and Open Science

    Science.gov (United States)

    Peters, Michael A.

    2010-01-01

    Open science is a term that is being used in the literature to designate a form of science based on open source models or that utilizes principles of open access, open archiving and open publishing to promote scientific communication. Open science increasingly also refers to open governance and more democratized engagement and control of science…

  18. OpenAPS Data Commons on Open Humans

    OpenAIRE

    Lewis, Dana M.; Ball, Madeleine

    2017-01-01

    Poster describing OpenAPS, Open Humans, and joint work creating a data commons for OpenAPS data in the Open Humans platform. Presented at the 2017 Sage Assembly Bionetworks Assembly and recipient of a Young Innovator/Investigator award.

  19. Keynesian Substantiation of the Marketing Policies in Local Development

    Directory of Open Access Journals (Sweden)

    Lucica MATEI

    2010-06-01

    Full Text Available The local development means the existence of several goods and services and their performance, expressed through adequate marketing policies, thus determining the overall development performance.The paper approaches the economic fundamental issues of local development and in this context it determines the basic components of public service marketing, relevant for local development: price, multiplier of revenues/expenditures, respectively the export multiplier.Those elements will express the ratios between resources and outcomes and their balance is based on a Keynesian model in an open economy.

  20. Diagnosis of a terminal deletion of 4p with duplication of Xp22.31 in a patient with findings of Opitz G/BBB syndrome and Wolf-Hirschhorn syndrome.

    Science.gov (United States)

    So, Joyce; Müller, Ines; Kunath, Melanie; Herrmann, Susanne; Ullmann, Reinhard; Schweiger, Susann

    2008-01-01

    Opitz G/BBB syndrome (OS) is a congenital midline malformation syndrome characterized by hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and cardiac defects. The X-linked form is caused by mutations in the MID1 gene, while no gene has yet been identified for the autosomal dominant form. Here, we report on a 15-year-old boy who was referred for MID1 mutation analysis with findings typical of OS, including apparent hypertelorism, hypospadias, a history of feeding difficulties, dysphagia secondary to esophageal arteria lusoria, growth retardation and developmental delay. No MID1 mutation was found, but subsequent sub-megabase resolution array CGH unexpectedly documented a 2.34 Mb terminal 4p deletion, suggesting a diagnosis of WHS, and a duplication in Xp22.31. Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving terminal chromosome 4p deletions, in particular 4p16.3. WHS is characterized by typical facial appearance ("Greek helmet facies"), mental retardation, congenital hypotonia, and growth retardation. While the severity of developmental delay in this patient supports the diagnosis of WHS rather than OS, this case illustrates the striking similarities of clinical findings in seemingly unrelated syndromes, suggesting common or interacting pathways at the molecular and pathogenetic level. This is the first report of arteria lusoria (esophageal vascular ring) in a patient with WHS. (c) 2007 Wiley-Liss, Inc.

  1. Pericardial effusion and pericardial compartments after open heart surgery

    International Nuclear Information System (INIS)

    Duvernoy, O.; Larsson, S.G.; Persson, K.; Thuren, J.; Wikstroem, G.; Akademiska Sjukhuset, Uppsala; Akademiska Sjukhuset, Uppsala

    1990-01-01

    Thirty-three patients with pericardial effusion after open heart surgery were investigated with computed tomography (CT). Twelve of the 33 patients also underwent echocardiography prior to pericardiocentesis. The effusions were typed according to the results of the CT investigation. Because of postoperative adhesions, typical patterns of localized pericardial effusions were found in 16 patients. The localized compartments were seen on the right and left side of the heart and around the aorta and the pulmonary artery. CT was therefore shown to be of value for selecting the approach for drainage with catheter pericardiocentesis. (orig.)

  2. 78 FR 75376 - State, Local, Tribal, and Private Sector Policy Advisory Committee (SLTP-PAC)

    Science.gov (United States)

    2013-12-11

    ...] State, Local, Tribal, and Private Sector Policy Advisory Committee (SLTP-PAC) AGENCY: National Archives... (NARA) announces a meeting of the State, Local, Tribal, and Private Sector Policy Advisory Committee... Information Program for State, Local, Tribal, and Private Sector Entities. The meeting will be open to the...

  3. Open innovation with an effective open innovation team.

    OpenAIRE

    Vanvoorden, Jonas

    2014-01-01

    This master's thesis explores how open innovation teams can successfully support open innovation inside of an organisation. Open innovation is a paradigm introduced by Henry Chesbrough (2003) a decade ago. It expands the innovation potential of organisations by opening them up to new ways of working with external partners. To implement open innovation, many companies rely on a small group of managers named open innovation teams. Although open innovation teams can potentially be vital for impl...

  4. From Open Source Software to Open Source Hardware

    OpenAIRE

    Viseur , Robert

    2012-01-01

    Part 2: Lightning Talks; International audience; The open source software principles progressively give rise to new initiatives for culture (free culture), data (open data) or hardware (open hardware). The open hardware is experiencing a significant growth but the business models and legal aspects are not well known. This paper is dedicated to the economics of open hardware. We define the open hardware concept and determine intellectual property tools we can apply to open hardware, with a str...

  5. Novel agents in CNS myeloma treatment.

    Science.gov (United States)

    Gozzetti, Alessandro; Cerase, Alfonso

    2014-01-01

    Central nervous system localization of multiple myeloma (CNS-MM) accounts for about 1% of all MM.Treatment is still unsatisfactory. Many treatments have been described in the literature: chemotherapy (CHT), intrathecal therapy (IT), and radiotherapy (RT), with survivals reported between one month and six months. Recent drugs such as the immunomodulatory drugs (IMiDs) and proteasome inhibitors (bortezomib) have changed the treatment of patients with MM, both younger and older, with a significant improvement in response and survival. The activity of new drugs in CNSMM has been reported but is still not well known. Bortezomib does not cross the blood brain barrier (BBB), and IMID’s seem to have only a minimal crossover. The role of novel agents in CNS MM management will be discussed as well as the potential role of other new immunomodulatory drugs (pomalidomide) and proteasome inhibitors that seem to cross the BBB and hold promise into the treatment of this rare and still incurable localization of the disease.

  6. Glucose transporter 1 and monocarboxylate transporters 1, 2, and 4 localization within the glial cells of shark blood-brain-barriers.

    Directory of Open Access Journals (Sweden)

    Carolina Balmaceda-Aguilera

    Full Text Available Although previous studies showed that glucose is used to support the metabolic activity of the cartilaginous fish brain, the distribution and expression levels of glucose transporter (GLUT isoforms remained undetermined. Optic/ultrastructural immunohistochemistry approaches were used to determine the expression of GLUT1 in the glial blood-brain barrier (gBBB. GLUT1 was observed solely in glial cells; it was primarily located in end-feet processes of the gBBB. Western blot analysis showed a protein with a molecular mass of 50 kDa, and partial sequencing confirmed GLUT1 identity. Similar approaches were used to demonstrate increased GLUT1 polarization to both apical and basolateral membranes in choroid plexus epithelial cells. To explore monocarboxylate transporter (MCT involvement in shark brain metabolism, the expression of MCTs was analyzed. MCT1, 2 and 4 were expressed in endothelial cells; however, only MCT1 and MCT4 were present in glial cells. In neurons, MCT2 was localized at the cell membrane whereas MCT1 was detected within mitochondria. Previous studies demonstrated that hypoxia modified GLUT and MCT expression in mammalian brain cells, which was mediated by the transcription factor, hypoxia inducible factor-1. Similarly, we observed that hypoxia modified MCT1 cellular distribution and MCT4 expression in shark telencephalic area and brain stem, confirming the role of these transporters in hypoxia adaptation. Finally, using three-dimensional ultrastructural microscopy, the interaction between glial end-feet and leaky blood vessels of shark brain was assessed in the present study. These data suggested that the brains of shark may take up glucose from blood using a different mechanism than that used by mammalian brains, which may induce astrocyte-neuron lactate shuttling and metabolic coupling as observed in mammalian brain. Our data suggested that the structural conditions and expression patterns of GLUT1, MCT1, MCT2 and MCT4 in shark

  7. Open-Ocean and Coastal Properties of Recent Major Tsunamis

    Science.gov (United States)

    Rabinovich, A.; Thomson, R.; Zaytsev, O.

    2017-12-01

    The properties of six major tsunamis during the period 2009-2015 (2009 Samoa; 2010 Chile; 2011 Tohoku; 2012 Haida Gwaii; 2014 and 2015 Chile) were thoroughly examined using coastal data from British Columbia, the U.S. West Coast and Mexico, and offshore open-ocean DART and NEPTUNE stations. Based on joint spectral analyses of the tsunamis and background noise, we have developed a method to suppress the influence of local topography and to use coastal observations to determine the underlying spectra of tsunami waves in the deep ocean. The "reconstructed" open-ocean tsunami spectra were found to be in close agreement with the actual tsunami spectra evaluated from the analysis of directly measured open-ocean tsunami records. We have further used the spectral estimates to parameterize tsunamis based on their integral open-ocean spectral characteristics. Three key parameters are introduced to describe individual tsunami events: (1) Integral open-ocean energy; (2) Amplification factor (increase of the mean coastal tsunami variance relative to the open-ocean variance); and (3) Tsunami colour, the frequency composition of the open-ocean tsunami waves. In particular, we found that the strongest tsunamis, associated with large source areas (the 2010 Chile and 2011 Tohoku) are "reddish" (indicating the dominance of low-frequency motions), while small-source events (the 2009 Samoa and 2012 Haida Gwaii) are "bluish" (indicating strong prevalence of high-frequency motions).

  8. Non-locality of non-Abelian anyons

    International Nuclear Information System (INIS)

    Brennen, G K; Iblisdir, S; Pachos, J K; Slingerland, J K

    2009-01-01

    Entangled states of quantum systems can give rise to measurement correlations of separated observers that cannot be described by local hidden variable theories. Usually, it is assumed that entanglement between particles is generated due to some distance-dependent interaction. Yet anyonic particles in two dimensions have a nontrivial interaction that is purely topological in nature. In other words, it does not depend on the distance between two particles, but rather on their exchange history. The information encoded in anyons is inherently non-local even in the single subsystem level making the treatment of anyons non-conventional. We describe a protocol to reveal the non-locality of anyons in terms of correlations in the outcomes of measurements in two separated regions. This gives a clear operational measure of non-locality for anyonic states and it opens up the possibility to test Bell inequalities in quantum Hall liquids or spin lattices.

  9. Non-locality of non-Abelian anyons

    Science.gov (United States)

    Brennen, G. K.; Iblisdir, S.; Pachos, J. K.; Slingerland, J. K.

    2009-10-01

    Entangled states of quantum systems can give rise to measurement correlations of separated observers that cannot be described by local hidden variable theories. Usually, it is assumed that entanglement between particles is generated due to some distance-dependent interaction. Yet anyonic particles in two dimensions have a nontrivial interaction that is purely topological in nature. In other words, it does not depend on the distance between two particles, but rather on their exchange history. The information encoded in anyons is inherently non-local even in the single subsystem level making the treatment of anyons non-conventional. We describe a protocol to reveal the non-locality of anyons in terms of correlations in the outcomes of measurements in two separated regions. This gives a clear operational measure of non-locality for anyonic states and it opens up the possibility to test Bell inequalities in quantum Hall liquids or spin lattices.

  10. Causal localizations in relativistic quantum mechanics

    Science.gov (United States)

    Castrigiano, Domenico P. L.; Leiseifer, Andreas D.

    2015-07-01

    Causal localizations describe the position of quantum systems moving not faster than light. They are constructed for the systems with finite spinor dimension. At the center of interest are the massive relativistic systems. For every positive mass, there is the sequence of Dirac tensor-localizations, which provides a complete set of inequivalent irreducible causal localizations. They obey the principle of special relativity and are fully Poincaré covariant. The boosters are determined by the causal position operator and the other Poincaré generators. The localization with minimal spinor dimension is the Dirac localization. Thus, the Dirac equation is derived here as a mere consequence of the principle of causality. Moreover, the higher tensor-localizations, not known so far, follow from Dirac's localization by a simple construction. The probability of localization for positive energy states results to be described by causal positive operator valued (PO-) localizations, which are the traces of the causal localizations on the subspaces of positive energy. These causal Poincaré covariant PO-localizations for every irreducible massive relativistic system were, all the more, not known before. They are shown to be separated. Hence, the positive energy systems can be localized within every open region by a suitable preparation as accurately as desired. Finally, the attempt is made to provide an interpretation of the PO-localization operators within the frame of conventional quantum mechanics attributing an important role to the negative energy states.

  11. Processing and utilization of soyabean in Toro local government ...

    African Journals Online (AJOL)

    Processing and utilization of soyabean in Toro local government area of Bauchi state, Nigeria. ... Open Access DOWNLOAD FULL TEXT ... from the farmers on their socio-economic characteristics, information sources and adoption of soybean ...

  12. Solar Open Flux Migration from Pole to Pole: Magnetic Field Reversal.

    Science.gov (United States)

    Huang, G-H; Lin, C-H; Lee, L C

    2017-08-25

    Coronal holes are solar regions with low soft X-ray or low extreme ultraviolet intensities. The magnetic fields from coronal holes extend far away from the Sun, and thus they are identified as regions with open magnetic field lines. Coronal holes are concentrated in the polar regions during the sunspot minimum phase, and spread to lower latitude during the rising phase of solar activity. In this work, we identify coronal holes with outward and inward open magnetic fluxes being in the opposite poles during solar quiet period. We find that during the sunspot rising phase, the outward and inward open fluxes perform pole-to-pole trans-equatorial migrations in opposite directions. The migration of the open fluxes consists of three parts: open flux areas migrating across the equator, new open flux areas generated in the low latitude and migrating poleward, and new open flux areas locally generated in the polar region. All three components contribute to the reversal of magnetic polarity. The percentage of contribution from each component is different for different solar cycle. Our results also show that the sunspot number is positively correlated with the lower-latitude open magnetic flux area, but negatively correlated with the total open flux area.

  13. OpenFOAM Analysis of CANDU-6 Moderator Flow

    International Nuclear Information System (INIS)

    Kim, Hyoung Tae; Chang, Se-Myong

    2015-01-01

    In this study OpenFOAM (Open Field Operation and Manipulation), an open source CFD solver, is used to simulate the three-dimensional moderator flow in calandria tank of CANDU-6 reactor improving the computational efficiency by parallel computing which does not need any proprietary license. A prototype of CANDU-6 reactor is numerically analyzed about three-dimensional moderator flow in calandrian tank with OpenFOAM, an open source CFD code. The horizontal fuel channels in a CANDU-6 reactor (a pressurized heavy water reactor) are submerged in the heavy water (D 2 O) pool which is contained by a cylindrical tank, calandria. Each fuel channel consists of concentric tubes: a Pressure Tube (PT) and a Calandria Tube (CT). And the CO 2 gas is filled between these tubes. Consequently, a heat flux is rapidly transferred to the outer CT so that a film boiling may occur in CT. As a result, it is important to keep the subcooling in the moderator. It is one of the major concerns in the CANDU safety analyses to estimate the local subcooling margin of the moderator inside the calandria tank. Previous experimental studies showed that the film boiling would be unlikely to occur if the local moderator subcooling is sufficient. Therefore, an accurate prediction of the moderator temperature distribution in the calandria tank is needed to confirm the channel integrity. There have been numerous computational efforts to estimate the thermal hydraulics in the calandria tank using CFD codes. Hadaller et al. obtained a tube bank pressure drop model for tube bundle region of the calandria tank and implemented it into the MODTURC C LAS code. Yoon et al. used the CFX code to develop a CFD model with a porous media approach for the core region. However, it is known that porous media modeling provide only average values of flow velocities and temperatures and do not give any information about local flow variables near tube solid walls, which are necessary to implement accurate heat transfer

  14. OpenFOAM Analysis of CANDU-6 Moderator Flow

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyoung Tae [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Chang, Se-Myong [Kunsan National University, Gunsan (Korea, Republic of)

    2015-10-15

    In this study OpenFOAM (Open Field Operation and Manipulation), an open source CFD solver, is used to simulate the three-dimensional moderator flow in calandria tank of CANDU-6 reactor improving the computational efficiency by parallel computing which does not need any proprietary license. A prototype of CANDU-6 reactor is numerically analyzed about three-dimensional moderator flow in calandrian tank with OpenFOAM, an open source CFD code. The horizontal fuel channels in a CANDU-6 reactor (a pressurized heavy water reactor) are submerged in the heavy water (D{sub 2}O) pool which is contained by a cylindrical tank, calandria. Each fuel channel consists of concentric tubes: a Pressure Tube (PT) and a Calandria Tube (CT). And the CO{sub 2} gas is filled between these tubes. Consequently, a heat flux is rapidly transferred to the outer CT so that a film boiling may occur in CT. As a result, it is important to keep the subcooling in the moderator. It is one of the major concerns in the CANDU safety analyses to estimate the local subcooling margin of the moderator inside the calandria tank. Previous experimental studies showed that the film boiling would be unlikely to occur if the local moderator subcooling is sufficient. Therefore, an accurate prediction of the moderator temperature distribution in the calandria tank is needed to confirm the channel integrity. There have been numerous computational efforts to estimate the thermal hydraulics in the calandria tank using CFD codes. Hadaller et al. obtained a tube bank pressure drop model for tube bundle region of the calandria tank and implemented it into the MODTURC{sub C}LAS code. Yoon et al. used the CFX code to develop a CFD model with a porous media approach for the core region. However, it is known that porous media modeling provide only average values of flow velocities and temperatures and do not give any information about local flow variables near tube solid walls, which are necessary to implement accurate heat

  15. Non-Supramenable Groups Acting on Locally Compact Spaces

    DEFF Research Database (Denmark)

    Kellerhals, Julian; Monod, Nicolas; Rørdam, Mikael

    2013-01-01

    Supramenability of groups is characterised in terms of invariant measures on locally compact spaces. This opens the door to constructing interesting crossed product $C^*$-algebras for non-supramenable groups. In particular, stable Kirchberg algebras in the UCT class are constructed using crossed ...

  16. Histamine Induces Alzheimer’s Disease-Like Blood Brain Barrier Breach and Local Cellular Responses in Mouse Brain Organotypic Cultures

    Directory of Open Access Journals (Sweden)

    Jonathan C. Sedeyn

    2015-01-01

    Full Text Available Among the top ten causes of death in the United States, Alzheimer’s disease (AD is the only one that cannot be cured, prevented, or even slowed down at present. Significant efforts have been exerted in generating model systems to delineate the mechanism as well as establishing platforms for drug screening. In this study, a promising candidate model utilizing primary mouse brain organotypic (MBO cultures is reported. For the first time, we have demonstrated that the MBO cultures exhibit increased blood brain barrier (BBB permeability as shown by IgG leakage into the brain parenchyma, astrocyte activation as evidenced by increased expression of glial fibrillary acidic protein (GFAP, and neuronal damage-response as suggested by increased vimentin-positive neurons occur upon histamine treatment. Identical responses—a breakdown of the BBB, astrocyte activation, and neuronal expression of vimentin—were then demonstrated in brains from AD patients compared to age-matched controls, consistent with other reports. Thus, the histamine-treated MBO culture system may provide a valuable tool in combating AD.

  17. From Open Source to Open Collaboration

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    Open source is the right to modify, not the right to contribute. Are external contributions absent from your project? Have you ever thought about what is it like to be a new contributor on your project? I challenge you to transform your project from Open Source to an Open Collaboration.

  18. OpenDolphin: presentation models for compelling user interfaces

    CERN Multimedia

    CERN. Geneva

    2014-01-01

    Shared applications run on the server. They still need a display, though, be it on the web or on the desktop. OpenDolphin introduces a shared presentation model to clearly differentiate between "what" to display and "how" to display. The "what" is managed on the server and is independent of the UI technology whereas the "how" can fully exploit the UI capabilities like the ubiquity of the web or the power of the desktop in terms of interactivity, animations, effects, 3D worlds, and local devices. If you run a server-centric architecture and still seek to provide the best possible user experience, then this talk is for you. About the speaker Dierk König (JavaOne Rock Star) works as a fellow for Canoo Engineering AG, Basel, Switzerland. He is a committer to many open-source projects including OpenDolphin, Groovy, Grails, GPars and GroovyFX. He is lead author of the "Groovy in Action" book, which is among ...

  19. Digitization and the open management of data: New prospects for electricity distributors

    International Nuclear Information System (INIS)

    Derdevet, Michel

    2017-01-01

    At the core of both the energy transition and the digital revolution are the grids for distributing electricity during this era of big data. The electricity grid is becoming smarter and smarter, as it is equipped with sensors capable of providing information and data - the leading example being the 35 million smart electricity meters to be installed in French households by 2021. Backed by recent legislation, the trend toward open data is, for distributors, both a requirement and a lever: an economic, social and environmental requirement for enabling localities to prove their sense of responsibility and for developing innovative services for citizens; but also a lever for distributors to become operators who, processing dynamic data, are open to their ecosystem - a lever for making new business models emerge for the local management of energy

  20. Violation of local realism with freedom of choice.

    Science.gov (United States)

    Scheidl, Thomas; Ursin, Rupert; Kofler, Johannes; Ramelow, Sven; Ma, Xiao-Song; Herbst, Thomas; Ratschbacher, Lothar; Fedrizzi, Alessandro; Langford, Nathan K; Jennewein, Thomas; Zeilinger, Anton

    2010-11-16

    Bell's theorem shows that local realistic theories place strong restrictions on observable correlations between different systems, giving rise to Bell's inequality which can be violated in experiments using entangled quantum states. Bell's theorem is based on the assumptions of realism, locality, and the freedom to choose between measurement settings. In experimental tests, "loopholes" arise which allow observed violations to still be explained by local realistic theories. Violating Bell's inequality while simultaneously closing all such loopholes is one of the most significant still open challenges in fundamental physics today. In this paper, we present an experiment that violates Bell's inequality while simultaneously closing the locality loophole and addressing the freedom-of-choice loophole, also closing the latter within a reasonable set of assumptions. We also explain that the locality and freedom-of-choice loopholes can be closed only within nondeterminism, i.e., in the context of stochastic local realism.

  1. Pulsed focused ultrasound combined with micro-bubble contrast agent can open the blood-brain barrier of gliblastoma patients and improve the efficacy of Temozolomide treatment

    Directory of Open Access Journals (Sweden)

    Qian DONG

    2017-06-01

    Full Text Available Objective This research examined the effect of microbubble contrast agent plus ultrasound on the permeability of blood-brain barrier, and explored whether it affects the efficacy of chemotherapeutic drugs on cerebral glioblastoma. Methods Wistar rats were divided into three groups to find the optimal concentration of ultrasonic contrast agent. To identify the best ultrasound mode that affected the permeability of blood brain barrier, we employed transmission electron microscopy for study of brain ultrastructure. Western blotting was used to detect the tight junction protein claudin-5. Evans blue staining of brain tissues was utilized to identify the best ultrasonic contrast agent concentration and mode. Rat glioma cells (line 9L were injected into Wistar rats. After temozolomide chemotherapy, the tumor size was measured and the tumor marker GFAP in serum was detected by ELISA. Results The best contrast agent concentration which increases permeability of BBB in rats was found to be 1ml/kg and the best ultrasound mode was intermittently- triggered pulses lasting for 10min (with interval was set at 400ms. More Evans blue passed the blood-brain barrier in ultrasonic cavitation effect group than in control group (P<0.05. After temozolomide chemotherapy, more tumor marker GFAP was detected in ultrasonic cavitation effect group than in control group (P<0.05. Conclusion The permeability of BBB was increased and more temozolomide went through BBB when the rats were subjected to intermittently triggered ultrasonic pulses and were injected at contrast agent at 1ml/kg, which could help to achieve better therapeutic efficacy for glioblastoma. DOI: 10.11855/j.issn.0577-7402.2017.05.06

  2. Local zoning ordinances -- how they limit or restrict mining

    International Nuclear Information System (INIS)

    Ingram, H.

    1991-01-01

    Local regulation of mining by zoning has taken place for a long period of time. The delegation to local municipalities of land use planning, zoning and nuisance abatement authority which may affect mining by state governments has been consistently upheld by appellate courts as valid exercises of the police power. Recently, mine operators and mineral owners have been confronted by efforts of local municipalities, often initiated by anti-mining citizen's groups, to impose more stringent restrictions on mining activities within their borders. In some situations, existing ordinances are being enforced for the first time, in others, new ordinances have been adopted without much awareness or involvement by the public. Enforced to the letter, these ordinances can sterilize large blocks of mineable reserves open-quotes operatingclose quotes or performance standards in excess of SMCRA-based regulatory requirements. It is fair to say that investigation of the potential impacts of local zoning and other related ordinances is essential in the planning for the expansion of existing operations or for new operations. There may be new rules in the game. This paper identifies problem areas in typical open-quotes modernclose quotes ordinances and discusses legal and constitutional issues which may arise by their enforcement in coal producing regions

  3. Identification of Reversible Disruption of the Human Blood-Brain Barrier Following Acute Ischemia.

    Science.gov (United States)

    Simpkins, Alexis N; Dias, Christian; Leigh, Richard

    2016-09-01

    Animal models of acute cerebral ischemia have demonstrated that diffuse blood-brain barrier (BBB) disruption can be reversible after early reperfusion. However, irreversible, focal BBB disruption in humans is associated with hemorrhagic transformation in patients receiving intravenous thrombolytic therapy. The goal of this study was to use a magnetic resonance imaging biomarker of BBB permeability to differentiate these 2 forms of BBB disruption. Acute stroke patients imaged with magnetic resonance imaging before, 2 hours after, and 24 hours after treatment with intravenous tissue-type plasminogen activator were included. The average BBB permeability of the acute ischemic region before and 2 hours after treatment was calculated using a T2* perfusion-weighted source images. Change in average permeability was compared with percent reperfusion using linear regression. Focal regions of maximal BBB permeability from the pretreatment magnetic resonance imaging were compared with the occurrence of parenchymal hematoma (PH) formation on the 24-hour magnetic resonance imaging scan using logistic regression. Signals indicating reversible BBB permeability were detected in 18/36 patients. Change in average BBB permeability correlated inversely with percent reperfusion (P=0.006), indicating that early reperfusion is associated with decreased BBB permeability, whereas sustained ischemia is associated with increased BBB disruption. Focal regions of maximal BBB permeability were significantly associated with subsequent formation of PH (P=0.013). This study demonstrates that diffuse, mild BBB disruption in the acutely ischemic human brain is reversible with reperfusion. This study also confirms prior findings that focal severe BBB disruption confers an increased risk of hemorrhagic transformation in patients treated with intravenous tissue-type plasminogen activator. © 2016 American Heart Association, Inc.

  4. Launching transverse-electric Localized Waves from a circular waveguide

    KAUST Repository

    Salem, Mohamed; Niver, Edip

    2011-01-01

    Axially symmetric transverse electric (TE) modes of a circular waveguide section are used to synthesize the vector TE Localized Wave (LW) field at the open end of the waveguide section. The necessary excitation coefficients of these modes

  5. Open Source, Openness, and Higher Education

    Science.gov (United States)

    Wiley, David

    2006-01-01

    In this article David Wiley provides an overview of how the general expansion of open source software has affected the world of education in particular. In doing so, Wiley not only addresses the development of open source software applications for teachers and administrators, he also discusses how the fundamental philosophy of the open source…

  6. Open Government and (Linked (Open (Government (Data

    Directory of Open Access Journals (Sweden)

    Christian Philipp Geiger

    2012-12-01

    Full Text Available This article explores the opening and the free usage of stored public sector data, supplied by state. In the age of Open Government and Open Data it’s not enough just to put data online. It should be rather weighed out whether, how and which supplied public sector data can be published. Open Data are defined as stored data which could be made accessible in a public interest without any restrictions for usage and distribution. These Open Data can possibly be statistics, geo data, maps, plans, environmental data and weather data in addition to materials of the parliaments, ministries and authorities. The preparation and the free access to existing data permit varied approaches to the reuse of data, discussed in the article. In addition, impulses can be given for Open Government – the opening of state and administration, to more transparency, participation and collaboration as well as to innovation and business development. The Open Data movement tries to get to the bottom of current publication processes in the public sector which could be formed even more friendly to citizens and enterprises.

  7. Early Blood-Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke.

    Science.gov (United States)

    Shi, Zhong-Song; Duckwiler, Gary R; Jahan, Reza; Tateshima, Satoshi; Szeder, Viktor; Saver, Jeffrey L; Kim, Doojin; Sharma, Latisha K; Vespa, Paul M; Salamon, Noriko; Villablanca, J Pablo; Viñuela, Fernando; Feng, Lei; Loh, Yince; Liebeskind, David S

    2018-05-01

    The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes. Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome. Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome. Copyright © 2018 by the American Society of Neuroimaging.

  8. Agronomic performance of locally adapted sweet potato ( Ipomoea ...

    African Journals Online (AJOL)

    Tissue culture techniques have opened a new frontier in agricultural science by addressing food security and agricultural production issues. A study was conducted to compare growth and yield characteristics between the tissue culture regenerated and conventionally propagated sweet potato cultivars. Five locally adapted ...

  9. Can Opening ‘Ethics Files’ on Medical Staff Improve Patients’ Care?

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Healthcare workers in Shanghai are walking the line after recent news that regulations issued by local health authorities will soon enforce the opening of an “ethics file” for each of the city’s 140,000 medical workers. According to the regulations, once

  10. Data networks and open systems

    International Nuclear Information System (INIS)

    Rosner, R.A.

    1985-01-01

    Computing in the LEP era will require a variety of communications facilities, ranging from high-speed local area networks forming the backbones of distributed control systems to wide area networks connecting data analysis centres together. The ISO model for Open Systems Interconnection (OSI) offers a possible framework for the general study of communications environments, whatever their performance parameters or geographical extent. This series of lectures uses the model as the basis for discussing elements of the communications hierarchy likely to be required for LEP computing. Examples are given of the practical application of OSI principles to real communications problems. (orig.)

  11. Local understanding of forest conservation in land use change dynamics

    DEFF Research Database (Denmark)

    Shaleh, Muhammad Adha; Guth, Miriam Karen; Rahman, Syed Ajijur

    2016-01-01

    Forest (SEPPSF), Malaysia. Nine in-depth interviews were conducted with Orang Asli Jakun living in SEPPSF using open-ended questions. Local communities have positive perspectives toward the forest conservation program, despite massive environmental changes in their living landscape. This study suggests......The success of local forest conservation program depends on a critical appreciation of local communities. Based on this understanding, the present study aims to explore people’s perspective of forest conservation in a context of changes in their living landscape at South East Pahang Peat Swamp...

  12. Experimental methods and transport models for drug delivery across the blood-brain barrier.

    Science.gov (United States)

    Fu, Bingmei M

    2012-06-01

    The blood-brain barrier (BBB) is a dynamic barrier essential for maintaining the micro-environment of the brain. Although the special anatomical features of the BBB determine its protective role for the central nervous system (CNS) from blood-born neurotoxins, however, the BBB extremely limits the therapeutic efficacy of drugs into the CNS, which greatly hinders the treatment of major brain diseases. This review summarized the unique structures of the BBB, described a variety of in vivo and in vitro experimental methods for determining the transport properties of the BBB, e.g., the permeability of the BBB to water, ions, and solutes including nutrients, therapeutic agents and drug carriers, and presented newly developed mathematical models which quantitatively correlate the anatomical structures of the BBB with its barrier functions. Finally, on the basis of the experimental observations and the quantitative models, several strategies for drug delivery through the BBB were proposed.

  13. Probabilistic Open Set Recognition

    Science.gov (United States)

    Jain, Lalit Prithviraj

    support vector machines. Building from the success of statistical EVT based recognition methods such as PI-SVM and W-SVM on the open set problem, we present a new general supervised learning algorithm for multi-class classification and multi-class open set recognition called the Extreme Value Local Basis (EVLB). The design of this algorithm is motivated by the observation that extrema from known negative class distributions are the closest negative points to any positive sample during training, and thus should be used to define the parameters of a probabilistic decision model. In the EVLB, the kernel distribution for each positive training sample is estimated via an EVT distribution fit over the distances to the separating hyperplane between positive training sample and closest negative samples, with a subset of the overall positive training data retained to form a probabilistic decision boundary. Using this subset as a frame of reference, the probability of a sample at test time decreases as it moves away from the positive class. Possessing this property, the EVLB is well-suited to open set recognition problems where samples from unknown or novel classes are encountered at test. Our experimental evaluation shows that the EVLB provides a substantial improvement in scalability compared to standard radial basis function kernel machines, as well as P I-SVM and W-SVM, with improved accuracy in many cases. We evaluate our algorithm on open set variations of the standard visual learning benchmarks, as well as with an open subset of classes from Caltech 256 and ImageNet. Our experiments show that PI-SVM, WSVM and EVLB provide significant advances over the previous state-of-the-art solutions for the same tasks.

  14. Open data and beyond : Exploring existing open data projects to prepare a successful open data strategy; Deelrapport inleiding open data

    NARCIS (Netherlands)

    Van Loenen, B.

    2012-01-01

    Netwerkbedrijf Alliander was begin 2011 zich aan het oriënteren naar de mogelijkheid om haar gegevens als open data ter beschikking te stellen aan een ieder. Echter wat open data nu precies is, welke mogelijke knelpunten moeten worden opgelost om open data te implementeren, de impact die open data

  15. Public open space for disaster mitigation in Tangerang housing estates

    Science.gov (United States)

    Winandari, M. I. R.

    2018-01-01

    Public open space in housing estates plays an important role particularly in disaster mitigation. In some housing, there are indications of shape and use of space changes post-handover to local government. The aim of this study is to explore the relationship between public open space condition and management related to disaster mitigation in Tangerang housing estates. Multiple case study method is used to analyse of 2 housing cases. Aspects of access and boundaries were used to evaluate the cases. The results showed that gated community housing type should have more than 1 access to facilitate evacuation by considering the farthest unit to the housing gate. This is necessary to provide open spaces that are easily accessible from all units as the first evacuation site during and post disaster.

  16. The OpenPMU Platform for Open Source Phasor Measurements

    OpenAIRE

    Laverty, David M.; Best, Robert J.; Brogan, Paul; Al-Khatib, Iyad; Vanfretti, Luigi; Morrow, D John

    2013-01-01

    OpenPMU is an open platform for the development of phasor measurement unit (PMU) technology. A need has been identified for an open-source alternative to commercial PMU devices tailored to the needs of the university researcher and for enabling the development of new synchrophasor instruments from this foundation. OpenPMU achieves this through open-source hardware design specifications and software source code, allowing duplicates of the OpenPMU to be fabricated under open-source licenses. Th...

  17. Colloquium: Non-Markovian dynamics in open quantum systems

    Science.gov (United States)

    Breuer, Heinz-Peter; Laine, Elsi-Mari; Piilo, Jyrki; Vacchini, Bassano

    2016-04-01

    The dynamical behavior of open quantum systems plays a key role in many applications of quantum mechanics, examples ranging from fundamental problems, such as the environment-induced decay of quantum coherence and relaxation in many-body systems, to applications in condensed matter theory, quantum transport, quantum chemistry, and quantum information. In close analogy to a classical Markovian stochastic process, the interaction of an open quantum system with a noisy environment is often modeled phenomenologically by means of a dynamical semigroup with a corresponding time-independent generator in Lindblad form, which describes a memoryless dynamics of the open system typically leading to an irreversible loss of characteristic quantum features. However, in many applications open systems exhibit pronounced memory effects and a revival of genuine quantum properties such as quantum coherence, correlations, and entanglement. Here recent theoretical results on the rich non-Markovian quantum dynamics of open systems are discussed, paying particular attention to the rigorous mathematical definition, to the physical interpretation and classification, as well as to the quantification of quantum memory effects. The general theory is illustrated by a series of physical examples. The analysis reveals that memory effects of the open system dynamics reflect characteristic features of the environment which opens a new perspective for applications, namely, to exploit a small open system as a quantum probe signifying nontrivial features of the environment it is interacting with. This Colloquium further explores the various physical sources of non-Markovian quantum dynamics, such as structured environmental spectral densities, nonlocal correlations between environmental degrees of freedom, and correlations in the initial system-environment state, in addition to developing schemes for their local detection. Recent experiments addressing the detection, quantification, and control of

  18. Open Data, Open Source and Open Standards in chemistry: The Blue Obelisk five years on

    Science.gov (United States)

    2011-01-01

    Background The Blue Obelisk movement was established in 2005 as a response to the lack of Open Data, Open Standards and Open Source (ODOSOS) in chemistry. It aims to make it easier to carry out chemistry research by promoting interoperability between chemistry software, encouraging cooperation between Open Source developers, and developing community resources and Open Standards. Results This contribution looks back on the work carried out by the Blue Obelisk in the past 5 years and surveys progress and remaining challenges in the areas of Open Data, Open Standards, and Open Source in chemistry. Conclusions We show that the Blue Obelisk has been very successful in bringing together researchers and developers with common interests in ODOSOS, leading to development of many useful resources freely available to the chemistry community. PMID:21999342

  19. [Medical globalization and local culture.

    Science.gov (United States)

    Paci, Eugenio

    2017-03-01

    Biomedical globalization is a reality in the presence of local worlds with growing human sufferance and inequalities. In this structural and cultural context, characterised by the new communication by Internet and social media, polarisation of medical and scientific debate is enhancing. Based on episodes related to public health issues like vaccines, the quest for better access of Italian professionals and public opinion to an open scientific debate on health research and practice is discussed.

  20. Global Drums and Local Masquerades

    Directory of Open Access Journals (Sweden)

    Liwhu Betiang

    2013-12-01

    Full Text Available TV broadcasting has been in Nigeria for more than 50 years (1959-2009. Its development has brought about a series of local responses to global socioeconomic and political environments and “soft” stimuli. This conclusion is based on a critical, interpretive reading of the history, form, and content of television in Nigeria from Obafemi Awolowo’s Western Nigeria Television in Ibadan through the federal government’s reactive establishment of the national network: the Nigeria Television Authority, and later, states and private television stations. The ultimate deregulation of television broadcasting in 1992, perceived as Babangida’s “politically-correct” reaction to the pressures from the Bretton Woods institutions, opened up national media markets for global penetration, and fast-tracked media globalization and its effects in Nigeria. While television stations in Nigeria have multiplied in numerical terms, programming/content/form have followed the global market/technological determinism turning Nigerian TV into localized versions of commercialized western master-scripts with very little local ideological direction.

  1. Diagnostic Yield of Microscopic Colitis in Open Access Endoscopy Center.

    Science.gov (United States)

    Ellingson, Derek; Miick, Ronald; Chang, Faye; Hillard, Robert; Choudhary, Abhishek; Ashraf, Imran; Bechtold, Matthew; Diaz-Arias, Alberto

    2011-08-01

    The diagnostic yield in open access endoscopy has been evaluated which generally support the effectiveness and efficiency of open access endoscopy. With a few exceptions, diagnostic yield studies have not been performed in open access endoscopy for more specific conditions. Therefore, we conducted a study to determine the efficiency of open access endoscopy in the detection of microscopic colitis as compared to traditional referral via a gastroenterologist. A retrospective search of the pathology database at the University of Missouri for specimens from a local open access endoscopy center was conducted via SNOMED code using the terms: "microscopic", "lymphocytic", "collagenous", "spirochetosis", "focal active colitis", "melanosis coli" and "histopathologic" in the diagnosis line for the time period between January 1, 2004 and May 25, 2006. Specimens and colonoscopy reports were reviewed by a single pathologist. Of 266 consecutive patients with chronic diarrhea and normal colonoscopies, the number of patients with microscopic disease are as follows: Lymphocytic colitis (n = 12, 4.5%), collagenous colitis (n = 17, 6.4%), focal active colitis (n = 15, 5.6%), and spirochetosis (n = 2, 0.4%). The diagnostic yield of microscopic colitis in this study of an open access endoscopy center does not differ significantly from that seen in major medical centers. In terms of diagnostic yield, open access endoscopy appears to be as effective in diagnosing microscopic colitis.

  2. Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats I: Magnetic resonance imaging.

    Science.gov (United States)

    van Vliet, Erwin A; Otte, Willem M; Wadman, Wytse J; Aronica, Eleonora; Kooij, Gijs; de Vries, Helga E; Dijkhuizen, Rick M; Gorter, Jan A

    2016-01-01

    The mammalian target of rapamycin (mTOR) pathway has received increasing attention as a potential antiepileptogenic target. Treatment with the mTOR inhibitor rapamycin after status epilepticus reduces the development of epilepsy in a rat model. To study whether rapamycin mediates this effect via restoration of blood-brain barrier (BBB) dysfunction, contrast-enhanced magnetic resonance imaging (CE-MRI) was used to determine BBB permeability throughout epileptogenesis. Imaging was repeatedly performed until 6 weeks after kainic acid-induced status epilepticus in rapamycin (6 mg/kg for 6 weeks starting 4 h after SE) and vehicle-treated rats, using gadobutrol as contrast agent. Seizures were detected using video monitoring in the week following the last imaging session. Gadobutrol leakage was widespread and extensive in both rapamycin and vehicle-treated epileptic rats during the acute phase, with the piriform cortex and amygdala as the most affected regions. Gadobutrol leakage was higher in rapamycin-treated rats 4 and 8 days after status epilepticus compared to vehicle-treated rats. However, during the chronic epileptic phase, gadobutrol leakage was lower in rapamycin-treated epileptic rats along with a decreased seizure frequency. This was confirmed by local fluorescein staining in the brains of the same rats. Total brain volume was reduced by this rapamycin treatment regimen. The initial slow recovery of BBB function in rapamycin-treated epileptic rats indicates that rapamycin does not reduce seizure activity by a gradual recovery of BBB integrity. The reduced BBB leakage during the chronic phase, however, could contribute to the decreased seizure frequency in post-status epilepticus rats treated with rapamycin. Furthermore, the data show that CE-MRI (using step-down infusion with gadobutrol) can be used as biomarker for monitoring the effect of drug therapy in rats. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  3. Developmental changes of l-arginine transport at the blood-brain barrier in rats.

    Science.gov (United States)

    Tachikawa, Masanori; Hirose, Shirou; Akanuma, Shin-Ichi; Matsuyama, Ryo; Hosoya, Ken-Ichi

    2018-05-01

    l-Arginine is required for regulating synapse formation/patterning and angiogenesis in the developing brain. We hypothesized that this requirement would be met by increased transporter-mediated supply across the blood-brain barrier (BBB). Thus, the purpose of this work was to test the idea that elevation of blood-to-brain l-arginine transport across the BBB in the postnatal period coincides with up-regulation of cationic acid transporter 1 (CAT1) expression in developing brain capillaries. We found that the apparent brain-to-plasma concentration ratio (Kp, app) of l-arginine after intravenous administration during the first and second postnatal weeks was 2-fold greater than that at the adult stage. Kp, app of l-serine was also increased at the first postnatal week. In contrast, Kp, app of d-mannitol, a passively BBB-permeable molecule, did not change, indicating that increased transport of l-arginine and l-serine is not due to BBB immaturity. Double immunohistochemical staining of CAT1 and a marker protein, glucose transporter 1, revealed that CAT1 was localized on both luminal and abluminal membranes of brain capillary endothelial cells during the developmental and adult stages. A dramatic increase in CAT1 expression in the brain was seen at postnatal day 7 (P7) and day 14 (P14) and the expression subsequently decreased as the brain matured. In accordance with this, intense immunostaining of CAT1 was observed in brain capillaries at P7 and P14. These findings strongly support our hypothesis and suggest that the supply of blood-born l-arginine to the brain via CAT1 at the BBB plays a key role in meeting the elevated demand for l-arginine in postnatal brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Challenging metastatic breast cancer with the natural defensin PvD1.

    Science.gov (United States)

    Figueira, Tiago N; Oliveira, Filipa D; Almeida, Inês; Mello, Érica O; Gomes, Valdirene M; Castanho, Miguel A R B; Gaspar, Diana

    2017-11-09

    Metastatic breast cancer is a very serious life threatening condition that poses many challenges for the pharmaceutical development of effective chemotherapeutics. As the therapeutics targeted to the localized masses in breast improve, metastatic lesions in the brain slowly increase in their incidence compromising successful treatment outcomes overall. The blood-brain-barrier (BBB) is one important obstacle for the management of breast cancer brain metastases. New therapeutic approaches are in demand for overcoming the BBB's breaching by breast tumor cells. In this work we demonstrate the potential dual role of a natural antimicrobial plant defensin, PvD 1 : it interferes with the formation of solid tumors in the breast and concomitantly controls adhesion of breast cancer cells to human brain endothelial cells. We have used a combination of techniques that probe PvD 1 's effect at the single cell level and reveal that this peptide can effectively damage breast tumor cells, leaving healthy breast and brain cells unaffected. Results suggest that PvD1 quickly internalizes in cancer cells but remains located in the membrane of normal cells with no significant damage to its structure and biomechanical properties. These interactions in turn modulate cell adhesiveness between tumor and BBB cells. PvD 1 is a potential template for the design of innovative pharmacological approaches for metastatic breast cancer treatment: the manipulation of the biomechanical properties of tumor cells that ultimately prevent their attachment to the BBB.

  5. Compact, open-architecture computed radiography system

    International Nuclear Information System (INIS)

    Huang, H.K.; Lim, A.; Kangarloo, H.; Eldredge, S.; Loloyan, M.; Chuang, K.S.

    1990-01-01

    Computed radiography (CR) was introduced in 1982, and its basic system design has not changed. Current CR systems have certain limitations: spatial resolution and signal-to-noise ratios are lower than those of screen-film systems, they are complicated and expensive to build, and they have a closed architecture. The authors of this paper designed and implemented a simpler, lower-cost, compact, open-architecture CR system to overcome some of these limitations. The open-architecture system is a manual-load-single-plate reader that can fit on a desk top. Phosphor images are stored in a local disk and can be sent to any other computer through standard interfaces. Any manufacturer's plate can be read with a scanning time of 90 second for a 35 x 43-cm plate. The standard pixel size is 174 μm and can be adjusted for higher spatial resolution. The data resolution is 12 bits/pixel over an x-ray exposure range of 0.01-100 mR

  6. Sharing Lessons-Learned on Effective Open Data, Open-Source Practices from OpenAQ, a Global Open Air Quality Community.

    Science.gov (United States)

    Hasenkopf, C. A.

    2017-12-01

    Increasingly, open data, open-source projects are unearthing rich datasets and tools, previously impossible for more traditional avenues to generate. These projects are possible, in part, because of the emergence of online collaborative and code-sharing tools, decreasing costs of cloud-based services to fetch, store, and serve data, and increasing interest of individuals to contribute their time and skills to 'open projects.' While such projects have generated palpable enthusiasm from many sectors, many of these projects face uncharted paths for sustainability, visibility, and acceptance. Our project, OpenAQ, is an example of an open-source, open data community that is currently forging its own uncharted path. OpenAQ is an open air quality data platform that aggregates and universally formats government and research-grade air quality data from 50 countries across the world. To date, we make available more than 76 million air quality (PM2.5, PM10, SO2, NO2, O3, CO and black carbon) data points through an open Application Programming Interface (API) and a user-customizable download interface at https://openaq.org. The goal of the platform is to enable an ecosystem of users to advance air pollution efforts from science to policy to the private sector. The platform is also an open-source project (https://github.com/openaq) and has only been made possible through the coding and data contributions of individuals around the world. In our first two years of existence, we have seen requests for data to our API skyrocket to more than 6 million datapoints per month, and use-cases as varied as ingesting data aggregated from our system into real-time models of wildfires to building open-source statistical packages (e.g. ropenaq and py-openaq) on top of the platform to creating public-friendly apps and chatbots. We will share a whirl-wind trip through our evolution and the many lessons learned so far related to platform structure, community engagement, organizational model type

  7. Quantum localization and bound-state formation in Bose-Einstein condensates

    International Nuclear Information System (INIS)

    Franzosi, Roberto; Giampaolo, Salvatore M.; Illuminati, Fabrizio

    2010-01-01

    We discuss the possibility of exponential quantum localization in systems of ultracold bosonic atoms with repulsive interactions in open optical lattices without disorder. We show that exponential localization occurs in the maximally excited state of the lowest energy band. We establish the conditions under which the presence of the upper energy bands can be neglected, determine the successive stages and the quantum phase boundaries at which localization occurs, and discuss schemes to detect it experimentally by visibility measurements. The discussed mechanism is a particular type of quantum localization that is intuitively understood in terms of the interplay between nonlinearity and a bounded energy spectrum.

  8. OpenSWPC: an open-source integrated parallel simulation code for modeling seismic wave propagation in 3D heterogeneous viscoelastic media

    Science.gov (United States)

    Maeda, Takuto; Takemura, Shunsuke; Furumura, Takashi

    2017-07-01

    We have developed an open-source software package, Open-source Seismic Wave Propagation Code (OpenSWPC), for parallel numerical simulations of seismic wave propagation in 3D and 2D (P-SV and SH) viscoelastic media based on the finite difference method in local-to-regional scales. This code is equipped with a frequency-independent attenuation model based on the generalized Zener body and an efficient perfectly matched layer for absorbing boundary condition. A hybrid-style programming using OpenMP and the Message Passing Interface (MPI) is adopted for efficient parallel computation. OpenSWPC has wide applicability for seismological studies and great portability to allowing excellent performance from PC clusters to supercomputers. Without modifying the code, users can conduct seismic wave propagation simulations using their own velocity structure models and the necessary source representations by specifying them in an input parameter file. The code has various modes for different types of velocity structure model input and different source representations such as single force, moment tensor and plane-wave incidence, which can easily be selected via the input parameters. Widely used binary data formats, the Network Common Data Form (NetCDF) and the Seismic Analysis Code (SAC) are adopted for the input of the heterogeneous structure model and the outputs of the simulation results, so users can easily handle the input/output datasets. All codes are written in Fortran 2003 and are available with detailed documents in a public repository.[Figure not available: see fulltext.

  9. Identity federation in OpenStack - an introduction to hybrid clouds

    Science.gov (United States)

    Denis, Marek; Castro Leon, Jose; Ormancey, Emmanuel; Tedesco, Paolo

    2015-12-01

    We are evaluating cloud identity federation available in the OpenStack ecosystem that allows for on premise bursting into remote clouds with use of local identities (i.e. domain accounts). Further enhancements to identity federation are a clear way to hybrid cloud architectures - virtualized infrastructures layered across independent private and public clouds.

  10. Performance evaluation of packet video transfer over local area networks

    OpenAIRE

    Lu, Jie

    1993-01-01

    This research investigates the implementation and performance of packet video transfer over local area networks. A network architecture is defined for packet video such that most of the processing is performed by the higher layers of the Open Systems Interconnection (OSI) reference model, while the lower layers provide real-time services. Implementation methods are discussed for coding schemes, including data compression, the network interface unit, and the underlying local are...

  11. A hybrid GA-TS algorithm for open vehicle routing optimization of coal mines material

    Energy Technology Data Exchange (ETDEWEB)

    Yu, S.W.; Ding, C.; Zhu, K.J. [China University of Geoscience, Wuhan (China)

    2011-08-15

    In the open vehicle routing problem (OVRP), the objective is to minimize the number of vehicles and the total distance (or time) traveled. This study primarily focuses on solving an open vehicle routing problem (OVRP) by applying a novel hybrid genetic algorithm and the Tabu search (GA-TS), which combines the GA's parallel computing and global optimization with TS's Tabu search skill and fast local search. Firstly, the proposed algorithm uses natural number coding according to the customer demands and the captivity of the vehicle for globe optimization. Secondly, individuals of population do TS local search with a certain degree of probability, namely, do the local routing optimization of all customer sites belong to one vehicle. The mechanism not only improves the ability of global optimization, but also ensures the speed of operation. The algorithm was used in Zhengzhou Coal Mine and Power Supply Co., Ltd.'s transport vehicle routing optimization.

  12. DESIGN AND IMPLEMENTATION OF AN OPEN ACCESS GEOPORTAL

    OpenAIRE

    SARI, Fatih

    2018-01-01

    GeoPortal Systems are being considered one of the most important object in interoperability concept for Spatial data Management. With the developing technology of the information age, the need for accessing to spatial data is caused to effort for establishing national, regional and local information systems by institutes and organizations. Sharing and accessing of spatial datasets between institutes and organizations are being more important within interoperability concept.In this study, Open...

  13. Quantum non-locality vs. quasi-local measurements in the conditions of the Aharonov-Bohm effect

    International Nuclear Information System (INIS)

    Gulian, Armen M

    2014-01-01

    Theoretical explanation of the Meissner effect involves proportionality between current density and vector potential, which has many deep consequences. As noticed by de Gennes, superconductors in a magnetic field 'find an equilibrium state where the sum of kinetic and magnetic energies is minimum' and this state 'corresponds to the expulsion of the magnetic field'. This statement still leaves an open question: from which source is the superconducting current acquiring its kinetic energy? A naïve answer, perhaps, is from the energy of the magnetic field. However, one can consider situations (Aharonov-Bohm effect), where the classical magnetic field is locally absent in the area occupied by the current. Experiments demonstrate that despite the local absence of the magnetic field, current is, nevertheless, building up. From what source is it acquiring its energy then? Locally, only a vector potential is present. How does the vector potential facilitate the formation of the current? Is the current formation a result of a truly non-local quantum action, or does the local action of the vector potential have experimental consequences? We discuss possible experiments with a hybrid normal-metal superconductor circuitry, which can clarify this puzzling situation. Experimental answers will be important for further developments.

  14. Evolution of open magnetic structures on the sun: the Skylab period

    International Nuclear Information System (INIS)

    Levine, R.H.

    1977-01-01

    High-resolution harmonic analysis of the measured photospheric magnetic field of the Sun is used to construct models of open magnetic structures over a period of 11 solar rotations. The models successfully reproduce the surface location and topology of all coronal holes during the Skylab period. In addition, there is persistent evidence in the models that open field lines are associated with active regions in a systematic way. These associations are listed for the period studied; they suggest that open field lines are a basic feature of solar magnetism. Specific examples of the evolution of coronal holes and of calculated open structures are presented. Quantitative study of the measured field strength within and neighboring a hole confirms the fact that coronal hole regions are indistinguishable by local magnetic properties. However, the calculated field strengths at the footpoints of open field lines within coronal holes show distinct evolutionary patterns and may indicate that, at least in young coronal holes, a significant amount of magnetic flux is closed. Problems of studying magnetic field divergence by using these models are discussed

  15. LRP1 in Brain Vascular Smooth Muscle Cells Mediates Local Clearance of Alzheimer's Amyloid-β

    OpenAIRE

    Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

    2012-01-01

    Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer’s disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-...

  16. The Physics of Open Ended Evolution

    Science.gov (United States)

    Adams, Alyssa M.

    What makes living systems different than non-living ones? Unfortunately this question is impossible to answer, at least currently. Instead, we must face computationally tangible questions based on our current understanding of physics, computation, information, and biology. Yet we have few insights into how living systems might quantifiably differ from their non-living counterparts, as in a mathematical foundation to explain away our observations of biological evolution, emergence, innovation, and organization. The development of a theory of living systems, if at all possible, demands a mathematical understanding of how data generated by complex biological systems changes over time. In addition, this theory ought to be broad enough as to not be constrained to an Earth-based biochemistry. In this dissertation, the philosophy of studying living systems from the perspective of traditional physics is first explored as a motivating discussion for subsequent research. Traditionally, we have often thought of the physical world from a bottom-up approach: things happening on a smaller scale aggregate into things happening on a larger scale. In addition, the laws of physics are generally considered static over time. Research suggests that biological evolution may follow dynamic laws that (at least in part) change as a function of the state of the system. Of the three featured research projects, cellular automata (CA) are used as a model to study certain aspects of living systems in two of them. These aspects include self-reference, open-ended evolution, local physical universality, subjectivity, and information processing. Open-ended evolution and local physical universality are attributed to the vast amount of innovation observed throughout biological evolution. Biological systems may distinguish themselves in terms of information processing and storage, not outside the theory of computation. The final research project concretely explores real-world phenomenon by means of

  17. Energy market opening and the national energy programme in Slovenia

    International Nuclear Information System (INIS)

    Tomsic, M. G.; Urbancic, A.

    2000-01-01

    Slovenia is now moving fast toward market opening, at least in the electricity sector, due to the new Energy Law adopted in 1999. The Energy Law defines the main energy policy directions, including the sustainable development criterion. It also calls for the preparation of a National Energy Programme (NEP) to be adopted by the Parliament. According to the Law, local governments are expected to prepare local energy concepts, in line with the NEP and space planning decisions. Two most difficult challenges for national energy policies are: opening of the electricity market and meeting the Kyoto Protocol targets in the reduction of greenhouse gasses. The success of the energy sector reform depends on the fine-tuning of various instruments: market structuring and state interventions. The immediate concern for the sector in the secondary legislation, the fifty regulations that the Energy Law calls for. These regulations have to be prepared well before the date of internal electricity market opening on April 15th, 2001. The institutional structure to be established should be adapted for international competition that will start in electricity and gas no later than January 1st, 2003. It is expected that the NEP, to be prepared by spring of the year 2001, will propose complementary development strategies to cope with partially conflicting targets. Four groups of criteria shall be applied to compare the alternatives: security of supply, competitiveness of the society, preserving the space and environment quality and social cohesion. It is expected that energy market opening, not a final goal by itself, can be instrumental for the improvement of the energy sector performance on all accounts. (author)

  18. Studies on performance of some open-pollinated maize cultivars in ...

    African Journals Online (AJOL)

    Plant density and nitrogen (N) fertilizer responses of one local and three improved open-pollinated cultivars of maize (Zea mays L.) developed in different eras of maize breeding were studied on sandy-loam Alfisols in the Guinea savanna zone of Ghana in 1992 and 1993. A split-plot design was used in which plant ...

  19. iELVis: An open source MATLAB toolbox for localizing and visualizing human intracranial electrode data.

    Science.gov (United States)

    Groppe, David M; Bickel, Stephan; Dykstra, Andrew R; Wang, Xiuyuan; Mégevand, Pierre; Mercier, Manuel R; Lado, Fred A; Mehta, Ashesh D; Honey, Christopher J

    2017-04-01

    Intracranial electrical recordings (iEEG) and brain stimulation (iEBS) are invaluable human neuroscience methodologies. However, the value of such data is often unrealized as many laboratories lack tools for localizing electrodes relative to anatomy. To remedy this, we have developed a MATLAB toolbox for intracranial electrode localization and visualization, iELVis. NEW METHOD: iELVis uses existing tools (BioImage Suite, FSL, and FreeSurfer) for preimplant magnetic resonance imaging (MRI) segmentation, neuroimaging coregistration, and manual identification of electrodes in postimplant neuroimaging. Subsequently, iELVis implements methods for correcting electrode locations for postimplant brain shift with millimeter-scale accuracy and provides interactive visualization on 3D surfaces or in 2D slices with optional functional neuroimaging overlays. iELVis also localizes electrodes relative to FreeSurfer-based atlases and can combine data across subjects via the FreeSurfer average brain. It takes 30-60min of user time and 12-24h of computer time to localize and visualize electrodes from one brain. We demonstrate iELVis's functionality by showing that three methods for mapping primary hand somatosensory cortex (iEEG, iEBS, and functional MRI) provide highly concordant results. COMPARISON WITH EXISTING METHODS: iELVis is the first public software for electrode localization that corrects for brain shift, maps electrodes to an average brain, and supports neuroimaging overlays. Moreover, its interactive visualizations are powerful and its tutorial material is extensive. iELVis promises to speed the progress and enhance the robustness of intracranial electrode research. The software and extensive tutorial materials are freely available as part of the EpiSurg software project: https://github.com/episurg/episurg. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Environmental and Genetic Factors Regulating Localization of the Plant Plasma Membrane H+-ATPase1[OPEN

    Science.gov (United States)

    Tan, Li Xuan; Bushey, Daniel B.; Swanson, Sarah J.

    2018-01-01

    A P-type H+-ATPase is the primary transporter that converts ATP to electrochemical energy at the plasma membrane of higher plants. Its product, the proton-motive force, is composed of an electrical potential and a pH gradient. Many studies have demonstrated that this proton-motive force not only drives the secondary transporters required for nutrient uptake, but also plays a direct role in regulating cell expansion. Here, we have generated a transgenic Arabidopsis (Arabidopsis thaliana) plant expressing H+-ATPase isoform 2 (AHA2) that is translationally fused with a fluorescent protein and examined its cellular localization by live-cell microscopy. Using a 3D imaging approach with seedlings grown for various times under a variety of light intensities, we demonstrate that AHA2 localization at the plasma membrane of root cells requires light. In dim light conditions, AHA2 is found in intracellular compartments, in addition to the plasma membrane. This localization profile was age-dependent and specific to cell types found in the transition zone located between the meristem and elongation zones. The accumulation of AHA2 in intracellular compartments is consistent with reduced H+ secretion near the transition zone and the suppression of root growth. By examining AHA2 localization in a knockout mutant of a receptor protein kinase, FERONIA, we found that the intracellular accumulation of AHA2 in the transition zone is dependent on a functional FERONIA-dependent inhibitory response in root elongation. Overall, this study provides a molecular underpinning for understanding the genetic, environmental, and developmental factors influencing root growth via localization of the plasma membrane H+-ATPase. PMID:29042459

  1. open-quotes Shift-Betelclose quotes: A (very) distributed mainframe

    International Nuclear Information System (INIS)

    Segal, B.; Martin, O.; Hassine, F.; Hemmer, F.; Jouanigot, J.M.

    1994-01-01

    Over the last four years, CERN has progressively converted its central batch production facilities from classic mainframe platforms (Cray XMP, IBM, ESA, Vax 9000) to distributed RISC based facilities, which have now attained a very large size. Both a CPU-intensive system (open-quotes CSFclose quotes, the Central Simulation Facility) and an I/O-intensive system (open-quotes SHIFTclose quotes, the Scaleable Heterogeneous Integrated Facility) have been developed, plus a distributed data management subsystem allowing seamless access to CERN'S central tape store and to large amounts of economical disk space. The full system is known as open-quotes COREclose quotes, the Centrally Operated Risc Environment; at the time of writing CORE comprises around 2000 CERN Units of Computing (about 8000 MIPs) and over a TeraByte of online disk space. This distributed system is connected using standard networking technologies (IP protocols over Ethernet, FDDI and UltraNet), but which until quite recently were only implemented at sufficiently high speed in the Local Area

  2. Methamphetamine Effects on Blood-Brain Barrier Structure and Function

    Directory of Open Access Journals (Sweden)

    Nicole Alia Northrop

    2015-03-01

    Full Text Available Methamphetamine (Meth is a widely abuse psychostimulant. Traditionally, studies have focused on the neurotoxic effects of Meth on monoaminergic neurotransmitter terminals. Recently, both in vitro and in vivo studies have investigated the effects of Meth on the BBB and found that Meth produces a decrease in BBB structural proteins and an increase in BBB permeability to various molecules. Moreover, preclinical studies are validated by clinical studies in which human Meth users have increased concentrations of toxins in the brain. Therefore, this review will focus on the structural and functional disruption of the BBB caused by Meth and the mechanisms that contribute to Meth-induced BBB disruption. The review will reveal that the mechanisms by which Meth damages dopamine and serotonin terminals are similar to the mechanisms by which the blood-brain barrier (BBB is damaged. Furthermore, this review will cover the factors that are known to potentiate the effects of Meth on the BBB, such as stress and HIV, both of which are co-morbid conditions associated with Meth abuse. Overall, the goal of this review is to demonstrate that the scope of damage produced by Meth goes beyond damage to monoaminergic neurotransmitter systems to include BBB disruption as well as provide a rationale for investigating therapeutics to treat Meth-induced BBB disruption. Since a breach of the BBB can have a multitude of consequences, therapies directed towards the treatment of BBB disruption may help to ameliorate the long-term neurodegeneration and cognitive deficits produced by Meth and possibly even Meth addiction.

  3. Antenna Deployment for the Localization of Partial Discharges in Open-Air Substations

    Science.gov (United States)

    Robles, Guillermo; Fresno, José Manuel; Sánchez-Fernández, Matilde; Martínez-Tarifa, Juan Manuel

    2016-01-01

    Partial discharges are ionization processes inside or on the surface of dielectrics that can unveil insulation problems in electrical equipment. The charge accumulated is released under certain environmental and voltage conditions attacking the insulation both physically and chemically. The final consequence of a continuous occurrence of these events is the breakdown of the dielectric. The electron avalanche provokes a derivative of the electric field with respect to time, creating an electromagnetic impulse that can be detected with antennas. The localization of the source helps in the identification of the piece of equipment that has to be decommissioned. This can be done by deploying antennas and calculating the time difference of arrival (TDOA) of the electromagnetic pulses. However, small errors in this parameter can lead to great displacements of the calculated position of the source. Usually, four antennas are used to find the source but the array geometry has to be correctly deployed to have minimal errors in the localization. This paper demonstrates, by an analysis based on simulation and also experimentally, that the most common layouts are not always the best options and proposes a simple antenna layout to reduce the systematic error in the TDOA calculation due to the positions of the antennas in the array. PMID:27092501

  4. Open Source Tools for Numerical Simulation of Urban Greenhouse Gas Emissions

    Science.gov (United States)

    Nottrott, A.; Tan, S. M.; He, Y.

    2016-12-01

    There is a global movement toward urbanization. Approximately 7% of the global population lives in just 28 megacities, occupying less than 0.1% of the total land area used by human activity worldwide. These cities contribute a significant fraction of the global budget of anthropogenic primary pollutants and greenhouse gasses. The 27 largest cities consume 9.9%, 9.3%, 6.7% and 3.0% of global gasoline, electricity, energy and water use, respectively. This impact motivates novel approaches to quantify and mitigate the growing contribution of megacity emissions to global climate change. Cities are characterized by complex topography, inhomogeneous turbulence, and variable pollutant source distributions. These features create a scale separation between local sources and urban scale emissions estimates known as the Grey-Zone. Modern computational fluid dynamics (CFD) techniques provide a quasi-deterministic, physically based toolset to bridge the scale separation gap between source level dynamics, local measurements, and urban scale emissions inventories. CFD has the capability to represent complex building topography and capture detailed 3D turbulence fields in the urban boundary layer. This presentation discusses the application of OpenFOAM to urban CFD simulations of natural gas leaks in cities. OpenFOAM is an open source software for advanced numerical simulation of engineering and environmental fluid flows. When combined with free or low cost computer aided drawing and GIS, OpenFOAM generates a detailed, 3D representation of urban wind fields. OpenFOAM was applied to model methane (CH4) emissions from various components of the natural gas distribution system, to investigate the impact of urban meteorology on mobile CH4 measurements. The numerical experiments demonstrate that CH4 concentration profiles are highly sensitive to the relative location of emission sources and buildings. Sources separated by distances of 5-10 meters showed significant differences in

  5. Exact results for ABJ Wilson loops and open-closed duality

    Energy Technology Data Exchange (ETDEWEB)

    Hatsuda, Yasuyuki [Département de Physique Théorique et section de Mathématiques, Université de Genève,Genève, CH-1211 (Switzerland); Okuyama, Kazumi [Department of Physics, Shinshu University,Matsumoto 390-8621 (Japan)

    2016-10-24

    We find new exact relations between the partition function and vacuum expectation values (VEVs) of 1/2 BPS Wilson loops in ABJ theory, which allow us to predict the large N expansions of the 1/2 BPS Wilson loops from known results of the partition function. These relations are interpreted as an open-closed duality where the closed string background is shifted by the insertion of Wilson loops due to a back-reaction. Using the connection between ABJ theory and the topological string on local ℙ{sup 1}×ℙ{sup 1}, we explicitly write down non-trivial relations between open and closed string amplitudes.

  6. Close connections between open science and open-source software

    Directory of Open Access Journals (Sweden)

    YouHua Chen

    2014-09-01

    Full Text Available Open science is increasingly gaining attention in recent years. In this mini-review, we briefly discuss and summarize the reasons of introducing open science into academic publications for scientists. We argue that open-source software (like R and Python software can be the universal and important platforms for doing open science because of their appealing features: open source, easy-reading document, commonly used in various scientific disciplines like statistics, chemistry and biology. At last, the challenges and future perspectives of performing open science are discussed.

  7. MR-guided preoperative localization and percutaneous core biopsy of suspicious breast lesions - experience on the vertically open 0.5 T system; MRT-gestuetzte Markierung und Stanzbiopsie suspekter Mammalaesionen. Moeglichkeiten und Erfahrungen an einem vertikal offenen 0,5-T-System

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, J.P.; Schulz, T.; Rueger, S.; Schmidt, F.; Kahn, T. [Universitaetsklinikum Leipzig (Germany). Klinik und Poliklinik fuer Diagnostische Radiologie; Horn, L.C. [Inst. fuer Pathologie, Universitaetsklinikum Leipzig (Germany); Leinung, S. [Chirurgische Klinik I, Universitaetsklinikum Leipzig (Germany); Briest, S. [Frauenklinik, Universitaetsklinikum Leipzig (Germany)

    2002-01-01

    Purpose. To evaluate the feasibility of performing breast interventions in a vertically open 0.5 T MR system (SIGNA SP/i, GE Medical Systems). To develop fitted equipment and to establish preoperative wire localization and percutaneous breast core biopsy as clinical routine procedures. Patients and methods. Initially, we applied a localization method with the patient placed in a sitting position in 31 cases using a single loop coil and a self-developed fixation device. Subsequently, 46 wire localizations and 28 percutaneous core biopsies were carried out in prone patient position using an open breast coil with an integrated biopsy device. The used instruments were either MR-compatible (18 G biopsy needle and localization wire, 14 G coaxial needle, prototype of a 16 G double-shoot gun) or MR-safe (double-shoot gun with 16 G needle). Results. After biopsy we found the needle tip (18 G for a wire localization and 14 G for a percutaneous core biopsy, respectively) placed either within or close to the lesions (<10 mm distance) for all patients. Out of a total of 66 benign lesions and 39 malignant tumors we missed the lesion (12 mm mean diameter, 4-25 mm range) during open biopsy in two cases and obtained a false negative result for one percutaneous biopsy of a 5 mm lesion. Conclusion. Preoperative wire localization and percutaneous core biopsy of suspicious breast lesions demonstrated by MRI can be carried out in a vertically open 0.5 T MR scanner. The degree of accuracy is comparable with that of X-ray or ultrasound-guided procedures. A follow-up has to be performed in cases with a negative biopsy. (orig.) [German] Zielsetzung. In den letzten Jahren wurde eine Vielzahl von Systemen zur praeoperativen Markierung oder Biopsie MRT-suspekter Mammalaesionen vorgestellt. Ziel unserer Untersuchungen war es, Moeglichkeiten solcher Verfahren an einem vertikal offenen 0,5-T-Magneten (SIGNA SP/i, GE Medical Systems) zu entwickeln, zu erproben und in die klinische Routine zu

  8. Open Solicitation System of Research and Development Ideas in JAPC

    Science.gov (United States)

    Yamamoto, Kazuhiko; Enami, Hisashi; Sakaiwaki, Yuuji; Nakayama, Yoshiyuki

    Open solicitation system of research and development ideas in The Japan Atomic Power Company (JAPC) is introduced. This system is established in 1999 to solve various subjects existing in JAPC's nuclear power stations by using highly advanced technique possessed by the enterprises or the organizations limited in Fukui Prefecture, and also to contribute them to become more advanced in their skill of technology. We have improved this system to make the results more applicable. We think it is important to coexist with the local community for the company engaged in nuclear energy as to cooperate together for the improvement of the local society.

  9. The Case of Open Leisure Activities Organized in Swedish Local Councils: The Role of Citizenship and Entrepreneurship Skills Development

    Science.gov (United States)

    Lindström, Lisbeth

    2016-01-01

    In this article, we contribute to theory by integrating literature on citizenship and entrepreneurship, based on which we develop a framework for how personal development is achieved for young people in the context of open leisure activities. The empirical material in this study consists of survey data collected in Swedish open leisure centers. A…

  10. Drug Delivery to the Brain in Alzheimer’s Disease: Consideration of the Blood-brain Barrier

    Science.gov (United States)

    Banks, William A.

    2012-01-01

    The successful treatment of Alzheimer’s disease (AD) will require drugs that can negotiate the blood-brain barrier (BBB). However, the BBB is not simply a physical barrier, but a complex interface that is in intimate communication with the rest of the central nervous system (CNS) and influenced by peripheral tissues. This review examines three aspects of the BBB in AD. First, it considers how the BBB may be contributing to the onset and progression of AD. In this regard, the BBB itself is a therapeutic target in the treatment of AD. Second, it examines how the BBB restricts drugs that might otherwise be useful in the treatment of AD and examines strategies being developed to deliver drugs to the CNS for the treatment of AD. Third, it considers how drug penetration across the AD BBB may differ from the BBB of normal aging. In this case, those differences can complicate the treatment of CNS diseases such as depression, delirium, psychoses, and pain control in the AD population. PMID:22202501

  11. The Blood Testis Barrier and Male Sexual Dysfunction following Spinal Cord Injury

    Science.gov (United States)

    2015-10-01

    non-invasive, Basso, Beattie, Bresnahan (BBB) open field locomotor test beginning on day 1 post-SCI. Briefly, this test scores rat hind limb...barrier integrity and enhances locomotor function in rats when given early following injury. During this third year, we have completed all planned...these SCI-induced pathologies within the testes long after cessation of licofelone treatment. Our results to date, are intriguing and suggest that SCI

  12. Distinct types of eigenvector localization in networks

    Science.gov (United States)

    Pastor-Satorras, Romualdo; Castellano, Claudio

    2016-01-01

    The spectral properties of the adjacency matrix provide a trove of information about the structure and function of complex networks. In particular, the largest eigenvalue and its associated principal eigenvector are crucial in the understanding of nodes’ centrality and the unfolding of dynamical processes. Here we show that two distinct types of localization of the principal eigenvector may occur in heterogeneous networks. For synthetic networks with degree distribution P(q) ~ q-γ, localization occurs on the largest hub if γ > 5/2 for γ < 5/2 a new type of localization arises on a mesoscopic subgraph associated with the shell with the largest index in the K-core decomposition. Similar evidence for the existence of distinct localization modes is found in the analysis of real-world networks. Our results open a new perspective on dynamical processes on networks and on a recently proposed alternative measure of node centrality based on the non-backtracking matrix.

  13. Incorporating 3D laparoscopy for the management of locally advanced cervical cancer: a comparison with open surgery.

    Science.gov (United States)

    Raspagliesi, Francesco; Bogani, Giorgio; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Scaffa, Cono; Sabatucci, Ilaria; Adorni, Marco; Lorusso, Domenica; Ditto, Antonino

    2016-08-03

    To test the effects of the implementation of 3D laparoscopic technology for the execution of nerve-sparing radical hysterectomy. Thirty patients undergoing nerve-sparing radical hysterectomy via 3D laparoscopic (3D-LNSRH, n = 10) or open surgery (NSRH, n = 20) were studied prospectively. No significant differences were observed in baseline patient characteristics. Operative times were similar between groups. We compared the first 10 patients undergoing 3D-LNSRH with the last 20 patients undergoing NSRH. Baseline characteristics were similar between groups (p>0.2). Patients undergoing 3D-LNSRH had longer operative time (264.4 ± 21.5 vs 217.2 ± 41.0 minutes; p = 0.005), lower blood loss (53.4 ± 26.1 vs 177.7 ± 96.0 mL; p<0.001), and shorter length of hospital stay (4.3 ± 1.2 vs 5.4 ± 0.7 days; p = 0.03) in comparison to patients undergoing open abdominal procedures. No intraoperative complication occurred. One (10%) patient had conversion to open surgery due to technical difficulties and the inability to insert the uterine manipulator. A trend towards higher complication (grade 2 or worse) rate was observed for patients undergoing NSRH in comparison to 3D-LNSRH (p = 0.06). Considering only severe complications (grade 3 or worse), no difference was observed (0/10 vs 2/20; p = 0.54). 3D-laparoscopic nerve-sparing radical hysterectomy is a safe and effective procedure. The implementation of 3D laparoscopic technology allows the execution of challenging operations via minimally invasive surgery, thus reducing open abdominal procedure rates. Further large prospective studies are warranted.

  14. Sharing open hardware through ROP, the robotic open platform

    NARCIS (Netherlands)

    Lunenburg, J.; Soetens, R.P.T.; Schoenmakers, F.; Metsemakers, P.M.G.; van de Molengraft, M.J.G.; Steinbuch, M.; Behnke, S.; Veloso, M.; Visser, A.; Xiong, R.

    2014-01-01

    The robot open source software community, in particular ROS, drastically boosted robotics research. However, a centralized place to exchange open hardware designs does not exist. Therefore we launched the Robotic Open Platform (ROP). A place to share and discuss open hardware designs. Among others

  15. Sharing open hardware through ROP, the Robotic Open Platform

    NARCIS (Netherlands)

    Lunenburg, J.J.M.; Soetens, R.P.T.; Schoenmakers, Ferry; Metsemakers, P.M.G.; Molengraft, van de M.J.G.; Steinbuch, M.

    2013-01-01

    The robot open source software community, in particular ROS, drastically boosted robotics research. However, a centralized place to exchange open hardware designs does not exist. Therefore we launched the Robotic Open Platform (ROP). A place to share and discuss open hardware designs. Among others

  16. Open Data, Open Specifications and Free and Open Source Software: A powerful mix to create distributed Web-based water information systems

    Science.gov (United States)

    Arias, Carolina; Brovelli, Maria Antonia; Moreno, Rafael

    2015-04-01

    We are in an age when water resources are increasingly scarce and the impacts of human activities on them are ubiquitous. These problems don't respect administrative or political boundaries and they must be addressed integrating information from multiple sources at multiple spatial and temporal scales. Communication, coordination and data sharing are critical for addressing the water conservation and management issues of the 21st century. However, different countries, provinces, local authorities and agencies dealing with water resources have diverse organizational, socio-cultural, economic, environmental and information technology (IT) contexts that raise challenges to the creation of information systems capable of integrating and distributing information across their areas of responsibility in an efficient and timely manner. Tight and disparate financial resources, and dissimilar IT infrastructures (data, hardware, software and personnel expertise) further complicate the creation of these systems. There is a pressing need for distributed interoperable water information systems that are user friendly, easily accessible and capable of managing and sharing large volumes of spatial and non-spatial data. In a distributed system, data and processes are created and maintained in different locations each with competitive advantages to carry out specific activities. Open Data (data that can be freely distributed) is available in the water domain, and it should be further promoted across countries and organizations. Compliance with Open Specifications for data collection, storage and distribution is the first step toward the creation of systems that are capable of interacting and exchanging data in a seamlessly (interoperable) way. The features of Free and Open Source Software (FOSS) offer low access cost that facilitate scalability and long-term viability of information systems. The World Wide Web (the Web) will be the platform of choice to deploy and access these systems

  17. Open Data as a key factor for developing expert systems: a perspective from Spain

    Directory of Open Access Journals (Sweden)

    Luz Andrea Rodríguez Rojas

    2013-06-01

    Full Text Available The open data movement is relatively new but very significant, and potentially powerful. The overall intention is to make local, regional and national data available in a form that allows for direct manipulation. This paper is based on analyzing the current context of the Open Data initiative in Spain, from its origins and concepts, the legal framework, current initiatives and challenges that must be addressed for effective reuse of public sector information.

  18. The blood-brain barrier in vitro using primary culture

    DEFF Research Database (Denmark)

    Larsen, Annette Burkhart

    The brain is protected from the entry of unwanted substances by means of the blood-brain barrier (BBB) formed by the brain microvasculature. This BBB is composed of non-fenestrated brain capillary endothelial cells (BCECs) with their intermingling tight junctions. The presence of the BBB is a huge...... obstacle for the treatment of central nervous system (CNS) diseases, as many potentially CNS active drugs are unable to reach their site of action within the brain. In vitro BBB models are, therefore, being developed to investigate the BBB permeability of a drug early in its development. The first part...... of the thesis involves the establishment and characterization of an in vitro BBB models based on primary cells isolated from the rat brain. Co-culture and triple culture models with astrocytes and pericytes were found to be the superior to mono cultured BCECs with respect to many important BBB characteristics...

  19. Building the Open Elements of an Open Data Competition

    NARCIS (Netherlands)

    d'Aquin, Mathieu; Dietze, Stefan; Drachsler, Hendrik; Guy, Marieke; Herder, Eelco; Parodi, Elisabetta

    2014-01-01

    The European Union is increasingly committed to pushing forward open approaches as indicated by the G8 Open Data Charter, the Opening Up Education initiative, the launch of the Open Education Europa Portal for OER resources and other similar initiatives. The EU-funded LinkedUp Project (Linking Web

  20. Helium-air exchange flows through partitioned opening and two-opening

    International Nuclear Information System (INIS)

    Kang, T. I.

    1997-01-01

    This paper describes experimental investigations of helium-air exchange flows through partitioned opening and two-opening. Such exchange flows may occur following rupture accident of stand pipe in high temperature engineering test reactor. A test vessel with the two types of small opening on top of test cylinder is used for experiments. An estimation method of mass increment is developed to measure the exchange flow rate. Upward flow of the helium and downward flow of the air in partitioned opening system interact out of entrance and exit of the opening. Therefore, an experiment with two-opening system is made to investigate effect of the fluids interaction of partitioned opening system. As a result of comparison of the exchange flow rates between two types of the opening system, it is demonstrated that the exchange flow rate of the two-opening system is larger than that of the partitioned opening system because of absence of the effect of fluids interaction. (author)

  1. Open government and municipalities: Beyond e-governement

    Directory of Open Access Journals (Sweden)

    Christian Cruz Meléndez

    2017-11-01

    Full Text Available This article’s purpose is to analyze egovernment and open government as tolos to strengthen the role of municipal government. It reviews the evolution of both tolos in Mexico and contains a conceptual analysis of both terms to gain an understanding of their meaning and of the reason why they are promoted for the benefit of local governments. Finally, it explores the availability of these tools in the municipalities, and how they contribute to each municipality in the fulfillment of its responsibilities.

  2. Gallbladder removal - open

    Science.gov (United States)

    Cholecystectomy - open; Gallbladder - open cholecystectomy; Cholecystitis - open cholecystectomy; Gallstones - open cholecystectomy ... a medical instrument called a laparoscope ( laparoscopic ... Open gallbladder surgery is used when laparoscopic surgery cannot ...

  3. Permeability of PEGylated immunoarsonoliposomes through in vitro blood brain barrier-medulloblastoma co-culture models for brain tumor therapy.

    Science.gov (United States)

    Al-Shehri, Abdulghani; Favretto, Marco E; Ioannou, Panayiotis V; Romero, Ignacio A; Couraud, Pierre-Olivier; Weksler, Babette Barbash; Parker, Terry L; Kallinteri, Paraskevi

    2015-03-01

    Owing to restricted access of pharmacological agents into the brain due to blood brain barrier (BBB) there is a need: 1. to develop a more representative 3-D-co-culture model of tumor-BBB interaction to investigate drug and nanoparticle transport into the brain for diagnostic and therapeutic evaluation. 2. to address the lack of new alternative methods to animal testing according to replacement-reduction-refinement principles. In this work, in vitro BBB-medulloblastoma 3-D-co-culture models were established using immortalized human primary brain endothelial cells (hCMEC/D3). hCMEC/D3 cells were cultured in presence and in absence of two human medulloblastoma cell lines on Transwell membranes. In vitro models were characterized for BBB formation, zonula occludens-1 expression and permeability to dextran. Transferrin receptors (Tfr) expressed on hCMEC/D3 were exploited to facilitate arsonoliposome (ARL) permeability through the BBB to the tumor by covalently attaching an antibody specific to human Tfr. The effect of anticancer ARLs on hCMEC/D3 was assessed. In vitro BBB and BBB-tumor co-culture models were established successfully. BBB permeability was affected by the presence of tumor aggregates as suggested by increased permeability of ARLs. There was a 6-fold and 8-fold increase in anti-Tfr-ARL uptake into VC312R and BBB-DAOY co-culture models, respectively, compared to plain ARLs. The three-dimensional models might be appropriate models to study the transport of various drugs and nanocarriers (liposomes and immunoarsonoliposomes) through the healthy and diseased BBB. The immunoarsonoliposomes can be potentially used as anticancer agents due to good tolerance of the in vitro BBB model to their toxic effect.

  4. Socio-economic assessment on maize production and adoption of open pollinated improved varieties in Dang, Nepal

    Directory of Open Access Journals (Sweden)

    Sanjiv Subedi

    2017-12-01

    Full Text Available Research was conducted from February to May, 2017 for socioeconomic assessment on maize production and adoption of open pollinated improved maize varieties in Dang district of Nepal. Altogether, 100 samples were taken by simple random sampling from the major maize growing areas and relevant publications were reviewed. Focal Group Discussion and Key Informant Survey were also done. Descriptive statistics, unpaired t-test, probit regression and indexing were used for data analysis using statistical tools- SPSS, STATA and MS-Excel. Probit econometric model revealed that ethnicity (1% level, gender (5% level, area under open pollinated improved maize (1% level, seed source dummy (1 % level and number of visits by farmers to agrovet (5% level significantly determined the adoption of open pollinated improved maize varieties. In addition, unpaired t-test revealed that the productivity of open pollinated improved maize varieties was significantly higher (at 1% level than local; also, the multinational companies' hybrids showed significantly higher productivity (at 1% level when compared to open pollinated improved varieties. Furthermore, indexing identified- lack of availability of quality seeds and fertilizers (I= 0.86 as the major problem associated with the maize production. Giving aggressive subsidy on open pollinated improved seeds and dealership to registered agrovets for selling the subsidy seeds could enhance the adoption. Moreover, government organizations working in the areas of agricultural extension and research must focus on adoption of open pollinated improved maize varieties among the farmers, substituting the local and developing the high yielding hybrid varieties in Nepal to increase the maize productivity.

  5. Open meta-search with OpenSearch: a case study

    OpenAIRE

    O'Riordan, Adrian P.

    2007-01-01

    The goal of this project was to demonstrate the possibilities of open source search engine and aggregation technology in a Web environment by building a meta-search engine which employs free open search engines and open protocols. In contrast many meta-search engines on the Internet use proprietary search systems. The search engines employed in this case study are all based on the OpenSearch protocol. OpenSearch-compliant systems support XML technologies such as RSS and Atom for aggregation a...

  6. "The Open Library at AU" (Athabasca University): Supporting Open Access and Open Educational Resources

    Science.gov (United States)

    Elliott, Colin; Fabbro, Elaine

    2015-01-01

    To address challenges that learners, course creators, librarians and academics involved with OER and MOOCs are facing when looking for scholarly materials, Athabasca University Library has initiated the development of "the Open Library at AU." This open library is a full library website that provides easy access to open and free…

  7. OpenMx: An Open Source Extended Structural Equation Modeling Framework

    Science.gov (United States)

    Boker, Steven; Neale, Michael; Maes, Hermine; Wilde, Michael; Spiegel, Michael; Brick, Timothy; Spies, Jeffrey; Estabrook, Ryne; Kenny, Sarah; Bates, Timothy; Mehta, Paras; Fox, John

    2011-01-01

    OpenMx is free, full-featured, open source, structural equation modeling (SEM) software. OpenMx runs within the "R" statistical programming environment on Windows, Mac OS-X, and Linux computers. The rationale for developing OpenMx is discussed along with the philosophy behind the user interface. The OpenMx data structures are…

  8. The local strength of microscopic alumina reinforcements

    International Nuclear Information System (INIS)

    Žagar, Goran; Pejchal, Václav; Mueller, Martin G.; Rossoll, Andreas; Cantoni, Marco; Mortensen, Andreas

    2015-01-01

    We measure, using an adaptation of a method designed for ceramic ball bearings, the local strength of a brittle second phase that serves to reinforce a metal. The method uses focused ion beam milling and a nanoindentation device, and is free of artifacts commonly present in micromachined specimens. It is demonstrated on Nextel 610™ nanocrystalline alumina fibers embedded in an aluminum matrix composite. Results reveal a size effect that does not follow, across size scales, usual Weibull statistics: the fiber strength distribution differs between measurements at the microscale and macroscopic tensile testing. This implies that, in micromechanical analysis of multiphase materials, highly localized events such as the propagation of internal damage require input data that must be measured at the same, local, microscale as the event; the present work opens a path to this end.

  9. Sex-specific signaling in the blood-brain barrier is required for male courtship in Drosophila.

    Directory of Open Access Journals (Sweden)

    Valbona Hoxha

    Full Text Available Soluble circulating proteins play an important role in the regulation of mating behavior in Drosophila melanogaster. However, how these factors signal through the blood-brain barrier (bbb to interact with the sex-specific brain circuits that control courtship is unknown. Here we show that male identity of the blood-brain barrier is necessary and that male-specific factors in the bbb are physiologically required for normal male courtship behavior. Feminization of the bbb of adult males significantly reduces male courtship. We show that the bbb-specific G-protein coupled receptor moody and bbb-specific Go signaling in adult males are necessary for normal courtship. These data identify sex-specific factors and signaling processes in the bbb as important regulators of male mating behavior.

  10. Plasma-ring, fast-opening switch

    International Nuclear Information System (INIS)

    Hartman, C.W.; Eddleman, J.; Hammer, J.H.

    1986-01-01

    The authors discuss a fast-opening switch concept based on magnetically confined plasma rings, PROS (for Plasma Ring Opening Switch). In PROS, the plasma ring, confined by Bθ /sub and B/poloidal /sub fields of a compact torus, provide a low mass, localized conduction path between coaxial electrodes. To operate the switch, driver current is passed across the electrodes through the ring, storing inductive energy in external inductance and between the electrodes on the driver side of the ring. The ring is accelerated away from the driver by the field of the driver current and passes over a load gap transferring the current to the load. The authors distinguish two configurations in PROS, straight PROS where the electrodes are coaxial cylinders, and cone PROS with conical electrodes. In straight PROS ring acceleration takes place during the inductive store period as in foil switches, but with the localized ring providing the current path. Increased performance is predicted for the cone PROS (see figure) which employs compression of the ring in the cone during the inductive store period. Here, the B/θ /sub field of the driver forces the ring towards the apex of the cone but the force is in near balance with the opposing component of the radial equilibrium force of the ring along the cone. As a result, the ring undergoes a slow, quasistatic compression limited only by resistive decay of the ring field. Slow compression allows inductive storage with low-power drivers (homopoloar, magneto cumulative generators, high C-low V capacitor banks, etc.). Near the apex of the cone, near peak compression, the ring is allowed to enter a straight coaxial section where, because of low-mass, it rapidly accelerates to high velocity and crosses the load gap

  11. Robotic assisted gastrectomy compared with open resection: a case-matched study.

    Science.gov (United States)

    Caruso, Riccardo; Vicente, Emilio; Quijano, Yolanda; Ielpo, Benedetto; Duran, Hipolito; Diaz, Eduardo; Fabra, Isabel; Ferri, Valentina

    2018-05-04

    In recent years, increasingly sophisticated tools have allowed for more complex robotic surgery. Robotic gastrectomy, however, is adopted in only a few selected centers. The goals of this study were to examine the adoption of robotic gastrectomy and to compare outcomes between open and robotic gastric resections. This is a case-matched analysis of patients who underwent robotic and open gastric resection performed at Sanchinarro University Hospital, Madrid from November 2011 to February 2017. Patient data were obtained retrospectively. Clinicopathologic characteristics and perioperative and postoperative outcomes were recorded and analyzed. Two groups of demographically similar patients were analyzed: the robotic group (n = 20) and the open surgery group (n = 19). The patient characteristics of the two groups have been compared. Robotic resection resulted in less blood loss, shorter postoperative hospital stay, and a longer operating time. The two groups had similar complication rates. Pathological data were similar for both procedures. Robotic gastrectomy for locally advanced gastric carcinoma is safe, and long-term outcomes are comparable to those patients who underwent open resection. Robotic gastrectomy resulted in a shorter hospital stay, less blood loss and morbidity comparable with the outcomes of open gastrectomy.

  12. Natural convection enhancement by a discrete vibrating plate and a cross-flow opening: a numerical investigation

    Science.gov (United States)

    Florio, L. A.; Harnoy, A.

    2011-06-01

    In this study, a unique combination of a vibrating plate and a cross-flow passage is proposed as a means of enhancing natural convection cooling. The enhancement potential was estimated based on numerical studies involving a representative model which includes a short, transversely oscillating plate, placed over a transverse cross-flow opening in a uniformly heated vertical channel wall dividing two adjacent vertical channels. The resulting velocity and temperature fields are analyzed, with the focus on the local thermal effects near the opening. The simulation indicates up to a 50% enhancement in the local heat transfer coefficient for vibrating plate amplitudes of at least 30% of the mean clearance space and frequencies of over 82 rad/s.

  13. Curious exceptions? : open source software and "open" technology

    NARCIS (Netherlands)

    Nuvolari, A.; Rullani, F.; St. Amant, Kirk; Still, Brian

    2007-01-01

    The aim of thts chapter is to explore the differences and commonalities between open source software and other cases of open technology. The concept of open technology is used here to indicate various models of innovation based on the participation of a wide range of different actors who freely

  14. Implementing Open Data: The Open Data Commons Project

    Directory of Open Access Journals (Sweden)

    Jordan Hatcher

    2008-02-01

    Full Text Available Free and libre/open source software (F/LOSS movements have spawned similar solutions in many other contexts, each at differing stages of development. As F/LOSS enters the routine and familiarity of middle age, the open content movement--open source for non-software copyright and best embodied by the work of Creative Commons--has just graduated university and is getting a feel for the world. Even younger is the open data movement, whose legal tools have just started to come online.

  15. The Effectiveness of Building Permit Regulation for Green Open Space at Housing Estates: Case Study of Kendal Regency, Central Java, Indonesia

    Science.gov (United States)

    Yulianti, Wiwik; Hadi, Sudharto P.

    2018-02-01

    Increasing demand for settlements steamed by population growth declines the quality of the environment specifically at urban area. The existing spatial planning could not able to prevent the change of land use for settlement and other infrastructures. The Act no. 26 of 2007 on spatial planning stipulates that green open space must reach 30% of the total area, consisting of 20% public open space and 10% private open space. The existing condition of urban area at Kendal Regency reach 245,6 million m2 with 88.145,5 m2 green open space or 0,036% out of total area. An effort to increase green open space in urban areas taken by the Government of Kendal Regency is by promulgating a local regulation stipulating that each housing developer request a building permit is obliged to provide a green open space at least 10 percent of the total housing area. This paper reviews the effectiveness of building permit regulation, the problems encountered and the concept proposed to make the local regulation work. The area of sample taken is three urban districts out of five urban districts, the resource persons chosen are those from relevant offices (Dinas) involved at the implementation of the local regulation. The data collection techniques employed are the Analytical Hierarchy Process (AHP), Geographic Information System (GIS) technology, social observation and informal interview. The data gathered will be analyzed quantitatively and qualitatively.

  16. The Effectiveness of Building Permit Regulation for Green Open Space at Housing Estates: Case Study of Kendal Regency, Central Java, Indonesia

    Directory of Open Access Journals (Sweden)

    Yulianti Wiwik

    2018-01-01

    Full Text Available Increasing demand for settlements steamed by population growth declines the quality of the environment specifically at urban area. The existing spatial planning could not able to prevent the change of land use for settlement and other infrastructures. The Act no. 26 of 2007 on spatial planning stipulates that green open space must reach 30% of the total area, consisting of 20% public open space and 10% private open space. The existing condition of urban area at Kendal Regency reach 245,6 million m2 with 88.145,5 m2 green open space or 0,036% out of total area. An effort to increase green open space in urban areas taken by the Government of Kendal Regency is by promulgating a local regulation stipulating that each housing developer request a building permit is obliged to provide a green open space at least 10 percent of the total housing area. This paper reviews the effectiveness of building permit regulation, the problems encountered and the concept proposed to make the local regulation work. The area of sample taken is three urban districts out of five urban districts, the resource persons chosen are those from relevant offices (Dinas involved at the implementation of the local regulation. The data collection techniques employed are the Analytical Hierarchy Process (AHP, Geographic Information System (GIS technology, social observation and informal interview. The data gathered will be analyzed quantitatively and qualitatively.

  17. Strategies for transporting nanoparticles across the blood-brain barrier.

    Science.gov (United States)

    Zhang, Tian-Tian; Li, Wen; Meng, Guanmin; Wang, Pei; Liao, Wenzhen

    2016-02-01

    The existence of blood-brain barrier (BBB) hampers the effective treatment of central nervous system (CNS) diseases. Almost all macromolecular drugs and more than 98% of small molecule drugs cannot pass the BBB. Therefore, the BBB remains a big challenge for delivery of therapeutics to the central nervous system. With the structural and mechanistic elucidation of the BBB under both physiological and pathological conditions, it is now possible to design delivery systems that could cross the BBB effectively. Because of their advantageous properties, nanoparticles have been widely deployed for brain-targeted delivery. This review paper presents the current understanding of the BBB under physiological and pathological conditions, and summarizes strategies and systems for BBB crossing with a focus on nanoparticle-based drug delivery systems. In summary, with wider applications and broader prospection the treatment of brain targeted therapy, nano-medicines have proved to be more potent, more specific and less toxic than traditional drug therapy.

  18. OpenSHS: Open Smart Home Simulator

    Directory of Open Access Journals (Sweden)

    Nasser Alshammari

    2017-05-01

    Full Text Available This paper develops a new hybrid, open-source, cross-platform 3D smart home simulator, OpenSHS, for dataset generation. OpenSHS offers an opportunity for researchers in the field of the Internet of Things (IoT and machine learning to test and evaluate their models. Following a hybrid approach, OpenSHS combines advantages from both interactive and model-based approaches. This approach reduces the time and efforts required to generate simulated smart home datasets. We have designed a replication algorithm for extending and expanding a dataset. A small sample dataset produced, by OpenSHS, can be extended without affecting the logical order of the events. The replication provides a solution for generating large representative smart home datasets. We have built an extensible library of smart devices that facilitates the simulation of current and future smart home environments. Our tool divides the dataset generation process into three distinct phases: first design: the researcher designs the initial virtual environment by building the home, importing smart devices and creating contexts; second, simulation: the participant simulates his/her context-specific events; and third, aggregation: the researcher applies the replication algorithm to generate the final dataset. We conducted a study to assess the ease of use of our tool on the System Usability Scale (SUS.

  19. OpenSHS: Open Smart Home Simulator.

    Science.gov (United States)

    Alshammari, Nasser; Alshammari, Talal; Sedky, Mohamed; Champion, Justin; Bauer, Carolin

    2017-05-02

    This paper develops a new hybrid, open-source, cross-platform 3D smart home simulator, OpenSHS, for dataset generation. OpenSHS offers an opportunity for researchers in the field of the Internet of Things (IoT) and machine learning to test and evaluate their models. Following a hybrid approach, OpenSHS combines advantages from both interactive and model-based approaches. This approach reduces the time and efforts required to generate simulated smart home datasets. We have designed a replication algorithm for extending and expanding a dataset. A small sample dataset produced, by OpenSHS, can be extended without affecting the logical order of the events. The replication provides a solution for generating large representative smart home datasets. We have built an extensible library of smart devices that facilitates the simulation of current and future smart home environments. Our tool divides the dataset generation process into three distinct phases: first design: the researcher designs the initial virtual environment by building the home, importing smart devices and creating contexts; second, simulation: the participant simulates his/her context-specific events; and third, aggregation: the researcher applies the replication algorithm to generate the final dataset. We conducted a study to assess the ease of use of our tool on the System Usability Scale (SUS).

  20. OpenQuake, a platform for collaborative seismic hazard and risk assessment

    Science.gov (United States)

    Henshaw, Paul; Burton, Christopher; Butler, Lars; Crowley, Helen; Danciu, Laurentiu; Nastasi, Matteo; Monelli, Damiano; Pagani, Marco; Panzeri, Luigi; Simionato, Michele; Silva, Vitor; Vallarelli, Giuseppe; Weatherill, Graeme; Wyss, Ben

    2013-04-01

    Sharing of data and risk information, best practices, and approaches across the globe is key to assessing risk more effectively. Through global projects, open-source IT development and collaborations with more than 10 regions, leading experts are collaboratively developing unique global datasets, best practice, tools and models for global seismic hazard and risk assessment, within the context of the Global Earthquake Model (GEM). Guided by the needs and experiences of governments, companies and international organisations, all contributions are being integrated into OpenQuake: a web-based platform that - together with other resources - will become accessible in 2014. With OpenQuake, stakeholders worldwide will be able to calculate, visualize and investigate earthquake hazard and risk, capture new data and share findings for joint learning. The platform is envisaged as a collaborative hub for earthquake risk assessment, used at global and local scales, around which an active network of users has formed. OpenQuake will comprise both online and offline tools, many of which can also be used independently. One of the first steps in OpenQuake development was the creation of open-source software for advanced seismic hazard and risk calculations at any scale, the OpenQuake Engine. Although in continuous development, a command-line version of the software is already being test-driven and used by hundreds worldwide; from non-profits in Central Asia, seismologists in sub-Saharan Africa and companies in South Asia to the European seismic hazard harmonization programme (SHARE). In addition, several technical trainings were organized with scientists from different regions of the world (sub-Saharan Africa, Central Asia, Asia-Pacific) to introduce the engine and other OpenQuake tools to the community, something that will continue to happen over the coming years. Other tools that are being developed of direct interest to the hazard community are: • OpenQuake Modeller; fundamental

  1. Opening up Education: The Collective Advancement of Education through Open Technology, Open Content, and Open Knowledge

    Science.gov (United States)

    Iiyoshi, Toru, Ed.; Kumar, M. S. Vijay, Ed.

    2008-01-01

    Given the abundance of open education initiatives that aim to make educational assets freely available online, the time seems ripe to explore the potential of open education to transform the economics and ecology of education. Despite the diversity of tools and resources already available--from well-packaged course materials to simple games, for…

  2. Conceptual Architecture of Building Energy Management Open Source Software (BEMOSS)

    Energy Technology Data Exchange (ETDEWEB)

    Khamphanchai, Warodom; Saha, Avijit; Rathinavel, Kruthika; Kuzlu, Murat; Pipattanasomporn, Manisa; Rahman, Saifur; Akyol, Bora A.; Haack, Jereme N.

    2014-12-01

    The objective of this paper is to present a conceptual architecture of a Building Energy Management Open Source Software (BEMOSS) platform. The proposed BEMOSS platform is expected to improve sensing and control of equipment in small- and medium-sized buildings, reduce energy consumption and help implement demand response (DR). It aims to offer: scalability, robustness, plug and play, open protocol, interoperability, cost-effectiveness, as well as local and remote monitoring. In this paper, four essential layers of BEMOSS software architecture -- namely User Interface, Application and Data Management, Operating System and Framework, and Connectivity layers -- are presented. A laboratory test bed to demonstrate the functionality of BEMOSS located at the Advanced Research Institute of Virginia Tech is also briefly described.

  3. A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model

    Directory of Open Access Journals (Sweden)

    Sara Neves-Coelho

    2017-10-01

    Full Text Available The capacity to transport therapeutic molecules across the blood–brain barrier (BBB represents a breakthrough in the development of tools for the treatment of many central nervous system (CNS-associated diseases. The BBB, while being protective against infectious agents, hinders the brain uptake of many drugs. Hence, finding safe shuttles able to overcome the BBB is of utmost importance. Herein, we identify a new BBB-translocating peptide with unique properties. For years it was thought that cationic sequences were mandatory for a cell-penetrating peptide (CPP to achieve cellular internalization. Despite being anionic at physiological pH, PepNeg (sequence (SGTQEEY is an efficient BBB translocator that is able to carry a large cargo (27 kDa, while maintaining BBB integrity. In addition, PepNeg is able to use two distinct methods of translocation, energy-dependent and -independent, suggesting that direct penetration might occur when low concentrations of peptide are presented to cells. The discovery of this new anionic trans-BBB peptide allows the development of new delivery systems to the CNS and contributes to the need to rethink the role of electrostatic attraction in BBB-translocation.

  4. Gpr124 is essential for blood-brain barrier integrity in central nervous system disease.

    Science.gov (United States)

    Chang, Junlei; Mancuso, Michael R; Maier, Carolina; Liang, Xibin; Yuki, Kanako; Yang, Lu; Kwong, Jeffrey W; Wang, Jing; Rao, Varsha; Vallon, Mario; Kosinski, Cynthia; Zhang, J J Haijing; Mah, Amanda T; Xu, Lijun; Li, Le; Gholamin, Sharareh; Reyes, Teresa F; Li, Rui; Kuhnert, Frank; Han, Xiaoyuan; Yuan, Jenny; Chiou, Shin-Heng; Brettman, Ari D; Daly, Lauren; Corney, David C; Cheshier, Samuel H; Shortliffe, Linda D; Wu, Xiwei; Snyder, Michael; Chan, Pak; Giffard, Rona G; Chang, Howard Y; Andreasson, Katrin; Kuo, Calvin J

    2017-04-01

    Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt-β-catenin signaling. Constitutive activation of Wnt-β-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124-CKO mice, with rescue of the endothelial gene tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption.

  5. Emulation of Equal Open Access and Competition Creation in the Wireline Telecommunications Local and Last Mile Market Segments

    Science.gov (United States)

    Van Epps, Daniel L.

    2013-01-01

    Expanded telecommunications was deemed a serious need for end users. The "Local Market" and "Last Mile" market segments have largely consolidated into "natural utilities". Competition and access problems occur if new providers enter the local market and desire competitive access and service to end users. Local and…

  6. A New Way of Measuring Openness: The Open Governance Index

    Directory of Open Access Journals (Sweden)

    Liz Laffan

    2012-01-01

    Full Text Available Open source software is now "business as usual" in the mobile industry. While much attention is given to the importance of open source licenses, we argue in this article that the governance model can be as necessary to a project’s success and that projects vary widely in the governance models – whether open or closed – that they employ. Open source governance models describe the control points that are used to influence open source projects with regard to access to the source code, how the source code is developed, how derivatives are created, and the community structure of the project. Governance determines who has control over the project beyond what is deemed legally necessary via the open source licenses for that project. The purpose of our research is to define and measure the governance of open source projects, in other words, the extent to which decision-making in an open source project is "open" or "closed". We analyzed eight open source projects using 13 specific governance criteria across four areas of governance: access, development, derivatives and community. Our findings suggest that the most open platforms will be most successful in the long term, however we acknowledge exceptions to this rule. We also identify best practices that are common across these open source projects with regard to source code access, development of source code, management of derivatives, and community structure. These best practices increase the likelihood of developer use of and involvement in open source projects.

  7. Spatial arrangement of faults and opening-mode fractures

    Science.gov (United States)

    Laubach, S. E.; Lamarche, J.; Gauthier, B. D. M.; Dunne, W. M.; Sanderson, David J.

    2018-03-01

    Spatial arrangement is a fundamental characteristic of fracture arrays. The pattern of fault and opening-mode fracture positions in space defines structural heterogeneity and anisotropy in a rock volume, governs how faults and fractures affect fluid flow, and impacts our understanding of the initiation, propagation and interactions during the formation of fracture patterns. This special issue highlights recent progress with respect to characterizing and understanding the spatial arrangements of fault and fracture patterns, providing examples over a wide range of scales and structural settings. Five papers describe new methods and improvements of existing techniques to quantify spatial arrangement. One study unravels the time evolution of opening-mode fracture spatial arrangement, which are data needed to compare natural patterns with progressive fracture growth in kinematic and mechanical models. Three papers investigate the role of evolving diagenesis in localizing fractures by mechanical stratigraphy and nine discuss opening-mode fracture spatial arrangement. Two papers show the relevance of complex cluster patterns to unconventional reservoirs through examples of fractures in tight gas sandstone horizontal wells, and a study of fracture arrangement in shale. Four papers demonstrate the roles of folds in fracture localization and the development spatial patterns. One paper models along-fault friction and fluid pressure and their effects on fault-related fracture arrangement. Contributions address deformation band patterns in carbonate rocks and fault size and arrangement above a detachment fault. Three papers describe fault and fracture arrangements in basement terrains, and three document fracture patterns in shale. This collection of papers points toward improvement in field methods, continuing improvements in computer-based data analysis and creation of synthetic fracture patterns, and opportunities for further understanding fault and fracture attributes in

  8. Local beam angle optimization with linear programming and gradient search

    International Nuclear Information System (INIS)

    Craft, David

    2007-01-01

    The optimization of beam angles in IMRT planning is still an open problem, with literature focusing on heuristic strategies and exhaustive searches on discrete angle grids. We show how a beam angle set can be locally refined in a continuous manner using gradient-based optimization in the beam angle space. The gradient is derived using linear programming duality theory. Applying this local search to 100 random initial angle sets of a phantom pancreatic case demonstrates the method, and highlights the many-local-minima aspect of the BAO problem. Due to this function structure, we recommend a search strategy of a thorough global search followed by local refinement at promising beam angle sets. Extensions to nonlinear IMRT formulations are discussed. (note)

  9. Open solicitation system of research and development ideas in JAPC

    International Nuclear Information System (INIS)

    Yamamoto, Kazuhiko; Enami, Hisashi; Sakaiwaki, Yuuji; Nakayama, Yoshiyuki

    2012-01-01

    Open solicitation system of research and development ideas in The Japan Atomic Power Company (JAPC) is introduced. This system is established in 1999 to solve various subjects existing in JAPC's nuclear power stations by using highly advanced technique possessed by the enterprises or the organizations limited in Fukui Prefecture, and also to contribute them to become more advanced in their skill of technology. We have improved this system to make the results more applicable. We think it is important to coexist with the local community for the company engaged in nuclear energy as to cooperate together for the improvement of the local society. (author)

  10. The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes.

    Directory of Open Access Journals (Sweden)

    Michael K DeSalvo

    2014-11-01

    Full Text Available AbstractCentral nervous system (CNS function is dependent on the stringent regulation of metabolites, drugs, cells, and pathogens exposed to the CNS space. Cellular blood-brain barrier (BBB structures are highly specific checkpoints governing entry and exit of all small molecules to and from the brain interstitial space, but the precise mechanisms that regulate the BBB are not well understood. In addition, the BBB has long been a challenging obstacle to the pharmacologic treatment of CNS diseases; thus model systems that can parse the functions of the BBB are highly desirable. In this study, we sought to define the transcriptome of the adult Drosophila melanogaster BBB by isolating the BBB surface glia with FACS and profiling their gene expression with microarrays. By comparing the transcriptome of these surface glia to that of all brain glia, brain neurons, and whole brains, we present a catalog of transcripts that are selectively enriched at the Drosophila BBB. We found that the fly surface glia show high expression of many ABC and SLC transporters, cell adhesion molecules, metabolic enzymes, signaling molecules, and components of xenobiotic metabolism pathways. Using gene sequence-based alignments, we compare the Drosophila and Murine BBB transcriptomes and discover many shared chemoprotective and small molecule control pathways, thus affirming the relevance of invertebrate models for studying evolutionary conserved BBB properties. The Drosophila BBB transcriptome is valuable to vertebrate and insect biologists alike as a resource for studying proteins underlying diffusion barrier development and maintenance, glial biology, and regulation of drug transport at tissue barriers.

  11. The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes.

    Science.gov (United States)

    DeSalvo, Michael K; Hindle, Samantha J; Rusan, Zeid M; Orng, Souvinh; Eddison, Mark; Halliwill, Kyle; Bainton, Roland J

    2014-01-01

    Central nervous system (CNS) function is dependent on the stringent regulation of metabolites, drugs, cells, and pathogens exposed to the CNS space. Cellular blood-brain barrier (BBB) structures are highly specific checkpoints governing entry and exit of all small molecules to and from the brain interstitial space, but the precise mechanisms that regulate the BBB are not well understood. In addition, the BBB has long been a challenging obstacle to the pharmacologic treatment of CNS diseases; thus model systems that can parse the functions of the BBB are highly desirable. In this study, we sought to define the transcriptome of the adult Drosophila melanogaster BBB by isolating the BBB surface glia with fluorescence activated cell sorting (FACS) and profiling their gene expression with microarrays. By comparing the transcriptome of these surface glia to that of all brain glia, brain neurons, and whole brains, we present a catalog of transcripts that are selectively enriched at the Drosophila BBB. We found that the fly surface glia show high expression of many ATP-binding cassette (ABC) and solute carrier (SLC) transporters, cell adhesion molecules, metabolic enzymes, signaling molecules, and components of xenobiotic metabolism pathways. Using gene sequence-based alignments, we compare the Drosophila and Murine BBB transcriptomes and discover many shared chemoprotective and small molecule control pathways, thus affirming the relevance of invertebrate models for studying evolutionary conserved BBB properties. The Drosophila BBB transcriptome is valuable to vertebrate and insect biologists alike as a resource for studying proteins underlying diffusion barrier development and maintenance, glial biology, and regulation of drug transport at tissue barriers.

  12. Computing OpenSURF on OpenCL and General Purpose GPU

    Directory of Open Access Journals (Sweden)

    Wanglong Yan

    2013-10-01

    Full Text Available Speeded-Up Robust Feature (SURF algorithm is widely used for image feature detecting and matching in computer vision area. Open Computing Language (OpenCL is a framework for writing programs that execute across heterogeneous platforms consisting of CPUs, GPUs, and other processors. This paper introduces how to implement an open-sourced SURF program, namely OpenSURF, on general purpose GPU by OpenCL, and discusses the optimizations in terms of the thread architectures and memory models in detail. Our final OpenCL implementation of OpenSURF is on average 37% and 64% faster than the OpenCV SURF v2.4.5 CUDA implementation on NVidia's GTX660 and GTX460SE GPUs, repectively. Our OpenCL program achieved real-time performance (>25 Frames Per Second for almost all the input images with different sizes from 320*240 to 1024*768 on NVidia's GTX660 GPU, NVidia's GTX460SE GPU and AMD's Radeon HD 6850 GPU. Our OpenCL approach on NVidia's GTX660 GPU is more than 22.8 times faster than its original CPU version on Intel's Dual-Core E5400 2.7G on average.

  13. Analyzing the blood-brain barrier: the benefits of medical imaging in research and clinical practice.

    Science.gov (United States)

    Chassidim, Yoash; Vazana, Udi; Prager, Ofer; Veksler, Ronel; Bar-Klein, Guy; Schoknecht, Karl; Fassler, Michael; Lublinsky, Svetlana; Shelef, Ilan

    2015-02-01

    A dysfunctional BBB is a common feature in a variety of brain disorders, a fact stressing the need for diagnostic tools designed to assess brain vessels' permeability in space and time. Biological research has benefited over the years various means to analyze BBB integrity. The use of biomarkers for improper BBB functionality is abundant. Systemic administration of BBB impermeable tracers can both visualize brain regions characterized by BBB impairment, as well as lead to its quantification. Additionally, locating molecular, physiological content in regions from which it is restricted under normal BBB functionality undoubtedly indicates brain pathology-related BBB disruption. However, in-depth research into the BBB's phenotype demands higher analytical complexity than functional vs. pathological BBB; criteria which biomarker based BBB permeability analyses do not meet. The involvement of accurate and engineering sciences in recent brain research, has led to improvements in the field, in the form of more accurate, sensitive imaging-based methods. Improvements in the spatiotemporal resolution of many imaging modalities and in image processing techniques, make up for the inadequacies of biomarker based analyses. In pre-clinical research, imaging approaches involving invasive procedures, enable microscopic evaluation of BBB integrity, and benefit high levels of sensitivity and accuracy. However, invasive techniques may alter normal physiological function, thus generating a modality-based impact on vessel's permeability, which needs to be corrected for. Non-invasive approaches do not affect proper functionality of the inspected system, but lack in spatiotemporal resolution. Nevertheless, the benefit of medical imaging, even in pre-clinical phases, outweighs its disadvantages. The innovations in pre-clinical imaging and the development of novel processing techniques, have led to their implementation in clinical use as well. Specialized analyses of vessels' permeability

  14. What affects local community hospitals' survival in turbulent times?

    Science.gov (United States)

    Chiang, Hung-Che; Wang, Shiow-Ing

    2015-06-01

    Hospital closures became a prevalent phenomenon in Taiwan after the implementation of a national health insurance program. A wide range of causes contributes to the viability of hospitals, but little is known about the situation under universal coverage health systems. The purpose of present study is to recognize the factors that may contribute to hospital survival under the universal coverage health system. This is a retrospective case-control study. Local community hospitals that contracted with the Bureau of National Health Insurance in 1998 and remained open during the period 1998-2011 are the designated cases. Controls are local community hospitals that closed during the same period. Using longitudinal representative health claim data, 209 local community hospitals that closed during 1998-2011 were compared with 165 that remained open. Variables related to institutional characteristics, degree of competition, characteristics of patients and financial performance were analyzed by logistic regression models. Hospitals' survival was positively related to specialty hospital, the number of respiratory care beds, the physician to population ratio, the number of clinics in the same region, a highly competitive market and the occupancy rate of elderly patients in the hospital. Teaching hospitals, investor-owned hospitals, the provision of obstetrics services or home care, and the number of medical centers or other local community hospitals may jeopardize the chance of survival. Factors-enhanced local hospitals to survive under the universal coverage health system have been identified. Hospital managers could manipulate these findings and adapt strategies for subsistence. © The Author 2015. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

  15. OpenSubspace

    DEFF Research Database (Denmark)

    Müller, Emmanuel; Assent, Ira; Günnemann, Stephan

    2009-01-01

    Subspace clustering and projected clustering are recent research areas for clustering in high dimensional spaces. As the field is rather young, there is a lack of comparative studies on the advantages and disadvantages of the different algorithms. Part of the underlying problem is the lack...... of available open source implementations that could be used by researchers to understand, compare, and extend subspace and projected clustering algorithms. In this paper, we discuss the requirements for open source evaluation software. We propose OpenSubspace, an open source framework that meets...... these requirements. OpenSubspace integrates state-of-the-art performance measures and visualization techniques to foster research in subspace and projected clustering....

  16. Open Babel: An open chemical toolbox

    Directory of Open Access Journals (Sweden)

    O'Boyle Noel M

    2011-10-01

    Full Text Available Abstract Background A frequent problem in computational modeling is the interconversion of chemical structures between different formats. While standard interchange formats exist (for example, Chemical Markup Language and de facto standards have arisen (for example, SMILES format, the need to interconvert formats is a continuing problem due to the multitude of different application areas for chemistry data, differences in the data stored by different formats (0D versus 3D, for example, and competition between software along with a lack of vendor-neutral formats. Results We discuss, for the first time, Open Babel, an open-source chemical toolbox that speaks the many languages of chemical data. Open Babel version 2.3 interconverts over 110 formats. The need to represent such a wide variety of chemical and molecular data requires a library that implements a wide range of cheminformatics algorithms, from partial charge assignment and aromaticity detection, to bond order perception and canonicalization. We detail the implementation of Open Babel, describe key advances in the 2.3 release, and outline a variety of uses both in terms of software products and scientific research, including applications far beyond simple format interconversion. Conclusions Open Babel presents a solution to the proliferation of multiple chemical file formats. In addition, it provides a variety of useful utilities from conformer searching and 2D depiction, to filtering, batch conversion, and substructure and similarity searching. For developers, it can be used as a programming library to handle chemical data in areas such as organic chemistry, drug design, materials science, and computational chemistry. It is freely available under an open-source license from http://openbabel.org.

  17. Open Babel: An open chemical toolbox

    Science.gov (United States)

    2011-01-01

    Background A frequent problem in computational modeling is the interconversion of chemical structures between different formats. While standard interchange formats exist (for example, Chemical Markup Language) and de facto standards have arisen (for example, SMILES format), the need to interconvert formats is a continuing problem due to the multitude of different application areas for chemistry data, differences in the data stored by different formats (0D versus 3D, for example), and competition between software along with a lack of vendor-neutral formats. Results We discuss, for the first time, Open Babel, an open-source chemical toolbox that speaks the many languages of chemical data. Open Babel version 2.3 interconverts over 110 formats. The need to represent such a wide variety of chemical and molecular data requires a library that implements a wide range of cheminformatics algorithms, from partial charge assignment and aromaticity detection, to bond order perception and canonicalization. We detail the implementation of Open Babel, describe key advances in the 2.3 release, and outline a variety of uses both in terms of software products and scientific research, including applications far beyond simple format interconversion. Conclusions Open Babel presents a solution to the proliferation of multiple chemical file formats. In addition, it provides a variety of useful utilities from conformer searching and 2D depiction, to filtering, batch conversion, and substructure and similarity searching. For developers, it can be used as a programming library to handle chemical data in areas such as organic chemistry, drug design, materials science, and computational chemistry. It is freely available under an open-source license from http://openbabel.org. PMID:21982300

  18. Early Experiences Writing Performance Portable OpenMP 4 Codes

    Energy Technology Data Exchange (ETDEWEB)

    Joubert, Wayne [ORNL; Hernandez, Oscar R [ORNL

    2016-01-01

    In this paper, we evaluate the recently available directives in OpenMP 4 to parallelize a computational kernel using both the traditional shared memory approach and the newer accelerator targeting capabilities. In addition, we explore various transformations that attempt to increase application performance portability, and examine the expressiveness and performance implications of using these approaches. For example, we want to understand if the target map directives in OpenMP 4 improve data locality when mapped to a shared memory system, as opposed to the traditional first touch policy approach in traditional OpenMP. To that end, we use recent Cray and Intel compilers to measure the performance variations of a simple application kernel when executed on the OLCF s Titan supercomputer with NVIDIA GPUs and the Beacon system with Intel Xeon Phi accelerators attached. To better understand these trade-offs, we compare our results from traditional OpenMP shared memory implementations to the newer accelerator programming model when it is used to target both the CPU and an attached heterogeneous device. We believe the results and lessons learned as presented in this paper will be useful to the larger user community by providing guidelines that can assist programmers in the development of performance portable code.

  19. Open problems in the geometry and analysis of Banach spaces

    CERN Document Server

    Guirao, Antonio J; Zizler, Václav

    2016-01-01

    This is a collection of some easily-formulated problems that remain open in the study of the geometry and analysis of Banach spaces. Assuming the reader has a working familiarity with the basic results of Banach space theory, the authors focus on concepts of basic linear geometry, convexity, approximation, optimization, differentiability, renormings, weak compact generating, Schauder bases and biorthogonal systems, fixed points, topology and nonlinear geometry. The main purpose of this work is to help convince young researchers in Functional Analysis that the theory of Banach spaces is a fertile field of research, full of interesting open problems. Inside the Banach space area, the text should help expose young researchers to the depth and breadth of the work that remains, and to provide the perspective necessary to choose a direction for further study. Some of the problems presented herein are longstanding open problems, some are recent, some are more important and some are only "local" problems. Some would ...

  20. Open source software and crowdsourcing for energy analysis

    International Nuclear Information System (INIS)

    Bazilian, Morgan; Rice, Andrew; Rotich, Juliana; Howells, Mark; DeCarolis, Joseph; Macmillan, Stuart; Brooks, Cameron; Bauer, Florian; Liebreich, Michael

    2012-01-01

    Informed energy decision making requires effective software, high-quality input data, and a suitably trained user community. Developing these resources can be expensive and time consuming. Even when data and tools are intended for public re-use they often come with technical, legal, economic and social barriers that make them difficult to adopt, adapt and combine for use in new contexts. We focus on the promise of open, publically accessible software and data as well as crowdsourcing techniques to develop robust energy analysis tools that can deliver crucial, policy-relevant insight, particularly in developing countries, where planning resources are highly constrained—and the need to adapt these resources and methods to the local context is high. We survey existing research, which argues that these techniques can produce high-quality results, and also explore the potential role that linked, open data can play in both supporting the modelling process and in enhancing public engagement with energy issues. - Highlights: ► We focus on the promise of open, publicly accessible software and data. ► These emerging techniques can produce high-quality results for energy analysis. ► Developing economies require new techniques for energy planning.

  1. Targeting multiple heterogeneous hardware platforms with OpenCL

    Science.gov (United States)

    Fox, Paul A.; Kozacik, Stephen T.; Humphrey, John R.; Paolini, Aaron; Kuller, Aryeh; Kelmelis, Eric J.

    2014-06-01

    The OpenCL API allows for the abstract expression of parallel, heterogeneous computing, but hardware implementations have substantial implementation differences. The abstractions provided by the OpenCL API are often insufficiently high-level to conceal differences in hardware architecture. Additionally, implementations often do not take advantage of potential performance gains from certain features due to hardware limitations and other factors. These factors make it challenging to produce code that is portable in practice, resulting in much OpenCL code being duplicated for each hardware platform being targeted. This duplication of effort offsets the principal advantage of OpenCL: portability. The use of certain coding practices can mitigate this problem, allowing a common code base to be adapted to perform well across a wide range of hardware platforms. To this end, we explore some general practices for producing performant code that are effective across platforms. Additionally, we explore some ways of modularizing code to enable optional optimizations that take advantage of hardware-specific characteristics. The minimum requirement for portability implies avoiding the use of OpenCL features that are optional, not widely implemented, poorly implemented, or missing in major implementations. Exposing multiple levels of parallelism allows hardware to take advantage of the types of parallelism it supports, from the task level down to explicit vector operations. Static optimizations and branch elimination in device code help the platform compiler to effectively optimize programs. Modularization of some code is important to allow operations to be chosen for performance on target hardware. Optional subroutines exploiting explicit memory locality allow for different memory hierarchies to be exploited for maximum performance. The C preprocessor and JIT compilation using the OpenCL runtime can be used to enable some of these techniques, as well as to factor in hardware

  2. International outreach for promoting open geoscience content in Finnish university libraries - libraries as the advocates of citizen science awareness on emerging open geospatial data repositories in Finnish society

    Science.gov (United States)

    Rousi, A. M.; Branch, B. D.; Kong, N.; Fosmire, M.

    2013-12-01

    In their Finnish National Spatial Strategy 2010-2015 the Finland's Ministry of Agriculture and Forestry delineated e.g. that spatial data skills should support citizens everyday activities and facilitate decision-making and participation of citizens. Studies also predict that open data, particularly open spatial data, would create, when fully realizing their potential, a 15% increase into the turnovers of Finnish private sector companies. Finnish libraries have a long tradition of serving at the heart of Finnish information society. However, with the emerging possibilities of educating their users on open spatial data a very few initiatives have been made. The National Survey of Finland opened its data in 2012. Finnish technology university libraries, such as Aalto University Library, are open environments for all citizens, and seem suitable of being the first thriving entities in educating citizens on open geospatial data. There are however many obstacles to overcome, such as lack of knowledge about policies, lack of understanding of geospatial data services and insufficient know-how of GIS software among the personnel. This framework examines the benefits derived from an international collaboration between Purdue University Libraries and Aalto University Library to create local strategies in implementing open spatial data education initiatives in Aalto University Library's context. The results of this international collaboration are explicated for the benefit of the field as a whole.

  3. Open Science and Open Data: Evolving Business Models

    OpenAIRE

    Melero, Remedios

    2013-01-01

    The rise of ICT has changed the way scientific inputs and outputs are disseminated and diffused. As a consequence, new business models for open access to Scientific publications and datasets are emerging. This session will explore the new features of the business models for open access and open data as well as the associated benefits and risks.

  4. TBI-Induced Formation of Toxic Tau and Its Biochemical Similarities to Tau in AD Brains

    Science.gov (United States)

    2017-10-01

    produces high quantities of protein (0.1-1.5mg tau from 1.5g of frozen tissue), preserves tau phosphorylation, and removes the vast majority of...disease This project seeks to establish extracellular soluble species of tau as major toxic species responsible for reduction of synaptic...competitive renewal grant is to optimize ultrasound parameters for non- invasive opening of the BBB. Dr. Lewis Brown 5R01MH098786-02 (Andrew J. Dwork

  5. OpenMI: the essential concepts and their implications for legacy software

    Science.gov (United States)

    Gregersen, J. B.; Gijsbers, P. J. A.; Westen, S. J. P.; Blind, M.

    2005-08-01

    Information & Communication Technology (ICT) tools such as computational models are very helpful in designing river basin management plans (rbmp-s). However, in the scientific world there is consensus that a single integrated modelling system to support e.g. the implementation of the Water Framework Directive cannot be developed and that integrated systems need to be very much tailored to the local situation. As a consequence there is an urgent need to increase the flexibility of modelling systems, such that dedicated model systems can be developed from available building blocks. The HarmonIT project aims at precisely that. Its objective is to develop and implement a standard interface for modelling components and other relevant tools: The Open Modelling Interface (OpenMI) standard. The OpenMI standard has been completed and documented. It relies entirely on the "pull" principle, where data are pulled by one model from the previous model in the chain. This paper gives an overview of the OpenMI standard, explains the foremost concepts and the rational behind it.

  6. Localization of multilayer networks by optimized single-layer rewiring.

    Science.gov (United States)

    Jalan, Sarika; Pradhan, Priodyuti

    2018-04-01

    We study localization properties of principal eigenvectors (PEVs) of multilayer networks (MNs). Starting with a multilayer network corresponding to a delocalized PEV, we rewire the network edges using an optimization technique such that the PEV of the rewired multilayer network becomes more localized. The framework allows us to scrutinize structural and spectral properties of the networks at various localization points during the rewiring process. We show that rewiring only one layer is enough to attain a MN having a highly localized PEV. Our investigation reveals that a single edge rewiring of the optimized MN can lead to the complete delocalization of a highly localized PEV. This sensitivity in the localization behavior of PEVs is accompanied with the second largest eigenvalue lying very close to the largest one. This observation opens an avenue to gain a deeper insight into the origin of PEV localization of networks. Furthermore, analysis of multilayer networks constructed using real-world social and biological data shows that the localization properties of these real-world multilayer networks are in good agreement with the simulation results for the model multilayer network. This paper is relevant to applications that require understanding propagation of perturbation in multilayer networks.

  7. Note: Tormenta: An open source Python-powered control software for camera based optical microscopy.

    Science.gov (United States)

    Barabas, Federico M; Masullo, Luciano A; Stefani, Fernando D

    2016-12-01

    Until recently, PC control and synchronization of scientific instruments was only possible through closed-source expensive frameworks like National Instruments' LabVIEW. Nowadays, efficient cost-free alternatives are available in the context of a continuously growing community of open-source software developers. Here, we report on Tormenta, a modular open-source software for the control of camera-based optical microscopes. Tormenta is built on Python, works on multiple operating systems, and includes some key features for fluorescence nanoscopy based on single molecule localization.

  8. What it means to be Zen: marked modulations of local and interareal synchronization during open monitoring meditation.

    Science.gov (United States)

    Hauswald, Anne; Übelacker, Teresa; Leske, Sabine; Weisz, Nathan

    2015-03-01

    Experienced meditators are able to voluntarily modulate their state of consciousness and attention. In the present study, we took advantage of this ability and studied brain activity related to the shift of mental state. Electrophysiological activity, i.e. EEG, was recorded from 11 subjects with varying degrees of meditation experience during Zen meditation (a form of open monitoring meditation) and during non-meditation rest. On a behavioral level, mindfulness scores were assessed using the Mindfulness Attention and Awareness Scale (MAAS). Analysis of EEG source power revealed the so far unreported finding that MAAS scores significantly correlated with gamma power (30-250Hz), particularly high-frequency gamma (100-245Hz), during meditation. High levels of mindfulness were related to increased high-frequency gamma, for example, in the cingulate cortex and somatosensory cortices. Further, we analyzed the relationship between connectivity during meditation and self-reported mindfulness (MAAS). We found a correlation between graph measures in the 160-170Hz range and MAAS scores. Higher levels of mindfulness were related to lower small worldedness as well as global and local clustering in paracentral, insular, and thalamic regions during meditation. In sum, the present study shows significant relationships of mindfulness and brain activity during meditation indicated by measures of oscillatory power and graph theoretical measures. The most prominent effects occur in brain structures crucially involved in processes of awareness and attention, which also show structural changes in short- and long-term meditators, suggesting continuative alterations in the meditating brain. Overall, our study reveals strong changes in ongoing oscillatory activity as well as connectivity patterns that appear to be sensitive to the psychological state changes induced by Zen meditation. Copyright © 2015. Published by Elsevier Inc.

  9. OpenGL Insights

    CERN Document Server

    Cozzi, Patrick

    2012-01-01

    Get Real-World Insight from Experienced Professionals in the OpenGL Community With OpenGL, OpenGL ES, and WebGL, real-time rendering is becoming available everywhere, from AAA games to mobile phones to web pages. Assembling contributions from experienced developers, vendors, researchers, and educators, OpenGL Insights presents real-world techniques for intermediate and advanced OpenGL, OpenGL ES, and WebGL developers. Go Beyond the Basics The book thoroughly covers a range of topics, including OpenGL 4.2 and recent extensions. It explains how to optimize for mobile devices, explores the design

  10. Local cabbage ( Brassica oleracea var. capitata L.) populations from ...

    African Journals Online (AJOL)

    In previous experiments, we were able to augment cabbages (Brassica oleracea L. var. capitata L.) with two new local open pollinated (OP) populations and one cultivar. The type of use indicated that these are cabbages with thinner and juicier leaves, which predisposes their heads for fine grating and also makes their ...

  11. The Application of MRI for Depiction of Subtle Blood Brain Barrier Disruption in Stroke

    OpenAIRE

    David Israeli, David Tanne, Dianne Daniels, David Last, Ran Shneor, David Guez, Efrat Landau, Yiftach Roth, Aharon Ocherashvilli, Mati Bakon, Chen Hoffman, Amit Weinberg, Talila Volk, Yael Mardor

    2011-01-01

    The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI...

  12. The Application of MRI for Depiction of Subtle Blood Brain Barrier Disruption in Stroke

    OpenAIRE

    Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

    2010-01-01

    The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI...

  13. Evidence-based management of postoperative pain in adults undergoing open inguinal hernia surgery

    DEFF Research Database (Denmark)

    Joshi, G P; Rawal, N; Kehlet, H

    2012-01-01

    BACKGROUND: Open inguinal hernia repair is associated with moderate postoperative pain, but optimal analgesia remains controversial. The aim of this systematic review was to evaluate the available literature on the management of pain after open hernia surgery. METHODS: Randomized studies......, in English, published between January 1966 and March 2009, assessing analgesic and anaesthetic interventions in adult open hernia surgery, and reporting pain scores, were retrieved from the Embase and MEDLINE databases. In addition to published evidence, clinical practice was taken into account to ensure...... and increased time to home-readiness compared with regional anaesthesia. CONCLUSION: Field block with, or without wound infiltration, either as a sole anaesthetic/analgesic technique or as an adjunct to general anaesthesia, is recommended to reduce postoperative pain. Continuous local anaesthetic infusion...

  14. Predicting the impact of urban flooding using open data.

    Science.gov (United States)

    Tkachenko, Nataliya; Procter, Rob; Jarvis, Stephen

    2016-05-01

    This paper aims to explore whether there is a relationship between search patterns for flood risk information on the Web and how badly localities have been affected by flood events. We hypothesize that localities where people stay more actively informed about potential flooding experience less negative impact than localities where people make less effort to be informed. Being informed, of course, does not hold the waters back; however, it may stimulate (or serve as an indicator of) such resilient behaviours as timely use of sandbags, relocation of possessions from basements to upper floors and/or temporary evacuation from flooded homes to alternative accommodation. We make use of open data to test this relationship empirically. Our results demonstrate that although aggregated Web search reflects average rainfall patterns, its eigenvectors predominantly consist of locations with similar flood impacts during 2014-2015. These results are also consistent with statistically significant correlations of Web search eigenvectors with flood warning and incident reporting datasets.

  15. High-efficiency one-dimensional atom localization via two parallel standing-wave fields

    International Nuclear Information System (INIS)

    Wang, Zhiping; Wu, Xuqiang; Lu, Liang; Yu, Benli

    2014-01-01

    We present a new scheme of high-efficiency one-dimensional (1D) atom localization via measurement of upper state population or the probe absorption in a four-level N-type atomic system. By applying two classical standing-wave fields, the localization peak position and number, as well as the conditional position probability, can be easily controlled by the system parameters, and the sub-half-wavelength atom localization is also observed. More importantly, there is 100% detecting probability of the atom in the subwavelength domain when the corresponding conditions are satisfied. The proposed scheme may open up a promising way to achieve high-precision and high-efficiency 1D atom localization. (paper)

  16. Selective Limbic Blood–Brain Barrier Breakdown in a Feline Model of Limbic Encephalitis with LGI1 Antibodies

    Science.gov (United States)

    Tröscher, Anna R.; Klang, Andrea; French, Maria; Quemada-Garrido, Lucía; Kneissl, Sibylle Maria; Bien, Christian G.; Pákozdy, Ákos; Bauer, Jan

    2017-01-01

    Human leucine-rich glioma-inactivated protein 1 encephalitis (LGI1) is an autoimmune limbic encephalitis in which serum and cerebrospinal fluid contain antibodies targeting LGI1, a protein of the voltage gated potassium channel (VGKC) complex. Recently, we showed that a feline model of limbic encephalitis with LGI1 antibodies, called feline complex partial seizures with orofacial involvement (FEPSO), is highly comparable to human LGI1 encephalitis. In human LGI1 encephalitis, neuropathological investigations are difficult because very little material is available. Taking advantage of this natural animal model to study pathological mechanisms will, therefore, contribute to a better understanding of its human counterpart. Here, we present a brain-wide histopathological analysis of FEPSO. We discovered that blood–brain barrier (BBB) leakage was present not only in all regions of the hippocampus but also in other limbic structures such as the subiculum, amygdale, and piriform lobe. However, in other regions, such as the cerebellum, no leakage was observed. In addition, this brain-region-specific immunoglobulin leakage was associated with the breakdown of endothelial tight junctions. Brain areas affected by BBB dysfunction also revealed immunoglobulin and complement deposition as well as neuronal cell death. These neuropathological findings were supported by magnetic resonance imaging showing signal and volume increase in the amygdala and the piriform lobe. Importantly, we could show that BBB disturbance in LGI1 encephalitis does not depend on T cell infiltrates, which were present brain-wide. This finding points toward another, so far unknown, mechanism of opening the BBB. The limbic predilection sites of immunoglobulin antibody leakage into the brain may explain why most patients with LGI1 antibodies have a limbic phenotype even though LGI1, the target protein, is ubiquitously distributed across the central nervous system. PMID:29093718

  17. Selective Limbic Blood–Brain Barrier Breakdown in a Feline Model of Limbic Encephalitis with LGI1 Antibodies

    Directory of Open Access Journals (Sweden)

    Anna R. Tröscher

    2017-10-01

    Full Text Available Human leucine-rich glioma-inactivated protein 1 encephalitis (LGI1 is an autoimmune limbic encephalitis in which serum and cerebrospinal fluid contain antibodies targeting LGI1, a protein of the voltage gated potassium channel (VGKC complex. Recently, we showed that a feline model of limbic encephalitis with LGI1 antibodies, called feline complex partial seizures with orofacial involvement (FEPSO, is highly comparable to human LGI1 encephalitis. In human LGI1 encephalitis, neuropathological investigations are difficult because very little material is available. Taking advantage of this natural animal model to study pathological mechanisms will, therefore, contribute to a better understanding of its human counterpart. Here, we present a brain-wide histopathological analysis of FEPSO. We discovered that blood–brain barrier (BBB leakage was present not only in all regions of the hippocampus but also in other limbic structures such as the subiculum, amygdale, and piriform lobe. However, in other regions, such as the cerebellum, no leakage was observed. In addition, this brain-region-specific immunoglobulin leakage was associated with the breakdown of endothelial tight junctions. Brain areas affected by BBB dysfunction also revealed immunoglobulin and complement deposition as well as neuronal cell death. These neuropathological findings were supported by magnetic resonance imaging showing signal and volume increase in the amygdala and the piriform lobe. Importantly, we could show that BBB disturbance in LGI1 encephalitis does not depend on T cell infiltrates, which were present brain-wide. This finding points toward another, so far unknown, mechanism of opening the BBB. The limbic predilection sites of immunoglobulin antibody leakage into the brain may explain why most patients with LGI1 antibodies have a limbic phenotype even though LGI1, the target protein, is ubiquitously distributed across the central nervous system.

  18. Selective Limbic Blood-Brain Barrier Breakdown in a Feline Model of Limbic Encephalitis with LGI1 Antibodies.

    Science.gov (United States)

    Tröscher, Anna R; Klang, Andrea; French, Maria; Quemada-Garrido, Lucía; Kneissl, Sibylle Maria; Bien, Christian G; Pákozdy, Ákos; Bauer, Jan

    2017-01-01

    Human leucine-rich glioma-inactivated protein 1 encephalitis (LGI1) is an autoimmune limbic encephalitis in which serum and cerebrospinal fluid contain antibodies targeting LGI1, a protein of the voltage gated potassium channel (VGKC) complex. Recently, we showed that a feline model of limbic encephalitis with LGI1 antibodies, called feline complex partial seizures with orofacial involvement (FEPSO), is highly comparable to human LGI1 encephalitis. In human LGI1 encephalitis, neuropathological investigations are difficult because very little material is available. Taking advantage of this natural animal model to study pathological mechanisms will, therefore, contribute to a better understanding of its human counterpart. Here, we present a brain-wide histopathological analysis of FEPSO. We discovered that blood-brain barrier (BBB) leakage was present not only in all regions of the hippocampus but also in other limbic structures such as the subiculum, amygdale, and piriform lobe. However, in other regions, such as the cerebellum, no leakage was observed. In addition, this brain-region-specific immunoglobulin leakage was associated with the breakdown of endothelial tight junctions. Brain areas affected by BBB dysfunction also revealed immunoglobulin and complement deposition as well as neuronal cell death. These neuropathological findings were supported by magnetic resonance imaging showing signal and volume increase in the amygdala and the piriform lobe. Importantly, we could show that BBB disturbance in LGI1 encephalitis does not depend on T cell infiltrates, which were present brain-wide. This finding points toward another, so far unknown, mechanism of opening the BBB. The limbic predilection sites of immunoglobulin antibody leakage into the brain may explain why most patients with LGI1 antibodies have a limbic phenotype even though LGI1, the target protein, is ubiquitously distributed across the central nervous system.

  19. Peptide gH625 enters into neuron and astrocyte cell lines and crosses the blood–brain barrier in rats

    Directory of Open Access Journals (Sweden)

    Valiante S

    2015-03-01

    Full Text Available Salvatore Valiante,1,* Annarita Falanga,2,3,* Luisa Cigliano,1 Giuseppina Iachetta,1 Rosa Anna Busiello,1 Valeria La Marca,1 Massimiliano Galdiero,4 Assunta Lombardi,1 Stefania Galdiero1,2 1Department of Biology, 2Department of Pharmacy, 3DFM Scarl, University of Naples Federico II, 4Department of Experimental Medicine, II University of Naples, Naples, Italy *These authors contributed equally to this paper and are considered joint first authors Abstract: Peptide gH625, derived from glycoprotein H of herpes simplex virus type 1, can enter cells efficiently and deliver a cargo. Nanoparticles armed with gH625 are able to cross an in vitro model of the blood–brain barrier (BBB. In the present study, in vitro experiments were performed to investigate whether gH625 can enter and accumulate in neuron and astrocyte cell lines. The ability of gH625 to cross the BBB in vivo was also evaluated. gH625 was administered in vivo to rats and its presence in the liver and in the brain was detected. Within 3.5 hours of intravenous administration, gH625 can be found beyond the BBB in proximity to cell neurites. gH625 has no toxic effects in vivo, since it does not affect the maximal oxidative capacity of the brain or the mitochondrial respiration rate. Our data suggest that gH625, with its ability to cross the BBB, represents a novel nanocarrier system for drug delivery to the central nervous system. These results open up new possibilities for direct delivery of drugs into patients in the field of theranostics and might address the treatment of several human diseases. Keywords: drug delivery, neurons, astrocytes, blood–brain barrier, peptide

  20. OpenTURNS, an open source uncertainty engineering software

    International Nuclear Information System (INIS)

    Popelin, A.L.; Dufoy, A.

    2013-01-01

    The needs to assess robust performances for complex systems have lead to the emergence of a new industrial simulation challenge: to take into account uncertainties when dealing with complex numerical simulation frameworks. EDF has taken part in the development of an Open Source software platform dedicated to uncertainty propagation by probabilistic methods, named OpenTURNS for Open source Treatment of Uncertainty, Risk and Statistics. OpenTURNS includes a large variety of qualified algorithms in order to manage uncertainties in industrial studies, from the uncertainty quantification step (with possibilities to model stochastic dependence thanks to the copula theory and stochastic processes), to the uncertainty propagation step (with some innovative simulation algorithms as the ziggurat method for normal variables) and the sensitivity analysis one (with some sensitivity index based on the evaluation of means conditioned to the realization of a particular event). It also enables to build some response surfaces that can include the stochastic modeling (with the chaos polynomial method for example). Generic wrappers to link OpenTURNS to the modeling software are proposed. At last, OpenTURNS is largely documented to provide rules to help use and contribution

  1. Mermin Non-Locality in Abstract Process Theories

    Directory of Open Access Journals (Sweden)

    Stefano Gogioso

    2015-11-01

    Full Text Available The study of non-locality is fundamental to the understanding of quantum mechanics. The past 50 years have seen a number of non-locality proofs, but its fundamental building blocks, and the exact role it plays in quantum protocols, has remained elusive. In this paper, we focus on a particular flavour of non-locality, generalising Mermin's argument on the GHZ state. Using strongly complementary observables, we provide necessary and sufficient conditions for Mermin non-locality in abstract process theories. We show that the existence of more phases than classical points (aka eigenstates is not sufficient, and that the key to Mermin non-locality lies in the presence of certain algebraically non-trivial phases. This allows us to show that fRel, a favourite toy model for categorical quantum mechanics, is Mermin local. We show Mermin non-locality to be the key resource ensuring the device-independent security of the HBB CQ (N,N family of Quantum Secret Sharing protocols. Finally, we challenge the unspoken assumption that the measurements involved in Mermin-type scenarios should be complementary (like the pair X,Y, opening the doors to a much wider class of potential experimental setups than currently employed. In short, we give conditions for Mermin non-locality tests on any number of systems, where each party has an arbitrary number of measurement choices, where each measurement has an arbitrary number of outcomes and further, that works in any abstract process theory.

  2. A Numerical and Experimental Study of Local Exhaust Capture Efficiency

    DEFF Research Database (Denmark)

    Madsen, U.; Breum, N. O.; Nielsen, Peter Vilhelm

    1993-01-01

    Direct capture efficiency of a local exhaust system is defined by introducing an imaginary control box surrounding the contaminant source and the exhaust opening. The imaginary box makes it possible to distinguish between contaminants directly captured and those that escape. Two methods for estim...... location is less important for the case studied. The choice of sampling strategy to obtain a representative background concentration is essential as substantial differences on direct capture efficiency are found. Recommendations are given......Direct capture efficiency of a local exhaust system is defined by introducing an imaginary control box surrounding the contaminant source and the exhaust opening. The imaginary box makes it possible to distinguish between contaminants directly captured and those that escape. Two methods...... for estimation of direct capture efficiency are given: (1) a numerical method based on the time-averaged Navier-Stokes equations for turbulent flows; and (2) a field method based on a representative background concentration. Direct capture efficiency is sensitive to the size of the control box, whereas its...

  3. Beyond Ambiguity: A Practical Framework for Developing and Implementing Open Government Reforms

    Directory of Open Access Journals (Sweden)

    Merlin Chatwin

    2017-12-01

    Full Text Available The broad idea of ‘Open Government’ is widely accepted as a facilitator for rebuilding trust and validation in governments around the world. The Open Government Partnership is a significant driver of this movement with over 75 member nations, 15 subnational government participants and many others local governments implementing reforms within their national frameworks. The central tenets of transparency, accountability, participation, and collaboration are well understood within scholarly works and practitioner publications. However, open government is yet to be attributed with a universally acknowledged definition. This leads to questions of adaptability and salience of the concept of open government across diverse contexts. This paper addresses these questions by utilizing a human systems framework called the Dialogue Boxes. To develop an understanding of how open government is currently positioned within scholarly works and practitioner publications, an extensive literature search was conducted. The search utilized major search engines, often-cited references, direct journal searches and colleague provided references. Using existing definitions and descriptions, this paper populates the framework with available information and allow for context specific content to be populated by future users. Ultimately, the aim of the paper is to support the development of open government action plans that maximize the direct positive impact on people’s lives.

  4. Dimensions of Openness

    DEFF Research Database (Denmark)

    Dalsgaard, Christian; Thestrup, Klaus

    2015-01-01

    The objective of the paper is to present a pedagogical approach to openness. The paper develops a framework for understanding the pedagogical opportunities of openness in education. Based on the pragmatism of John Dewey and sociocultural learning theory, the paper defines openness in education...... as a matter of engaging educational activities in sociocultural practices of a surrounding society. Openness is not only a matter of opening up the existing, but of developing new educational practices that interact with society. The paper outlines three pedagogical dimensions of openness: transparency...... practices. Openness as joint engagement in the world aims at establishing interdependent collaborative relationships between educational institutions and external practices. To achieve these dimensions of openness, educational activities need to change and move beyond the course as the main format...

  5. In vitro blood-brain barrier permeability predictions for GABAA receptor modulating piperine analogs.

    Science.gov (United States)

    Eigenmann, Daniela Elisabeth; Dürig, Carmen; Jähne, Evelyn Andrea; Smieško, Martin; Culot, Maxime; Gosselet, Fabien; Cecchelli, Romeo; Helms, Hans Christian Cederberg; Brodin, Birger; Wimmer, Laurin; Mihovilovic, Marko D; Hamburger, Matthias; Oufir, Mouhssin

    2016-06-01

    The alkaloid piperine from black pepper (Piper nigrum L.) and several synthetic piperine analogs were recently identified as positive allosteric modulators of γ-aminobutyric acid type A (GABAA) receptors. In order to reach their target sites of action, these compounds need to enter the brain by crossing the blood-brain barrier (BBB). We here evaluated piperine and five selected analogs (SCT-66, SCT-64, SCT-29, LAU397, and LAU399) regarding their BBB permeability. Data were obtained in three in vitro BBB models, namely a recently established human model with immortalized hBMEC cells, a human brain-like endothelial cells (BLEC) model, and a primary animal (bovine endothelial/rat astrocytes co-culture) model. For each compound, quantitative UHPLC-MS/MS methods in the range of 5.00-500ng/mL in the corresponding matrix were developed, and permeability coefficients in the three BBB models were determined. In vitro predictions from the two human BBB models were in good agreement, while permeability data from the animal model differed to some extent, possibly due to protein binding of the screened compounds. In all three BBB models, piperine and SCT-64 displayed the highest BBB permeation potential. This was corroborated by data from in silico prediction. For the other piperine analogs (SCT-66, SCT-29, LAU397, and LAU399), BBB permeability was low to moderate in the two human BBB models, and moderate to high in the animal BBB model. Efflux ratios (ER) calculated from bidirectional permeability experiments indicated that the compounds were likely not substrates of active efflux transporters. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. OpenOffice y el formato OpenDocument: funciones y compatibilidad

    OpenAIRE

    Codina, Lluís; Rovira, Cristòfol

    2008-01-01

    Presentation of the OpenOffice suite and the ODF format. The basic characteristics of OpenOffice and ODF format are presented. The need for the adoption of open-source software and open formats is discussed. Finally, an ODF case study of converting xhtml documents related to an e-learning course is presented.

  7. Morphofunctional aspects of the blood-brain barrier.

    Science.gov (United States)

    Nico, Beatrice; Ribatti, Domenico

    2012-01-01

    The blood-brain barrier (BBB) selectively controls the homeostasis of the Central Nervous System (CNS) environment by the specific structural and biochemical features of the endothelial cells, pericytes and glial endfeet, which represent the cellular components of the mature BBB. Endothelial tight junctions (TJs) are the most important structural component of the BBB, and molecular alteration in the phosphorylation state of some TJs proteins, like ZO-1 or occludin, are crucial in determining alterations in the control of BBB vascular permeability. Astrocytes endfeet enveloping the vessels wall, are considered important in the induction and maintenance of the BBB, through secretion of soluble factors, which modulate the expression of enzymatic complexes and antigens by endothelial cells and TJs - associated proteins. Moreover, astrocytes control water flux at BBB site by expressing a specific water channel, namely aquaporin-4 (AQP4), involved in the molecular composition of the orthogonal particles arrays (OAPs) on the perivascular glial endfeet and tightly coupled with the maintenance of the BBB integrity. Disruption of the BBB is a consistent event occurring in the development of several CNS diseases, including demyelinating lesions in the course of relapsing multiple sclerosis, stroke, Duchenne muscular dystrophy (DMD), but also mechanical injures, neurological insults, septic encephalopathy, brain tumors, permanent ischemia or transient ischemia followed by reperfusion. In most cases, these pathological conditions are associated with an increase in microvascular permeability, vasogenic edema, swollen atrocyte endfeet, and BBB disruption.

  8. Delivery of Biologics Across the Blood-Brain Barrier with Molecular Trojan Horse Technology.

    Science.gov (United States)

    Pardridge, William M

    2017-12-01

    Biologics are potential new therapeutics for many diseases of the central nervous system. Biologics include recombinant lysosomal enzymes, neurotrophins, decoy receptors, and therapeutic antibodies. These are large molecule drugs that do not cross the blood-brain barrier (BBB). All classes of biologics have been tested, without success, in clinical trials of brain disease over the last 25 years. In none of these past clinical trials was the biologic re-engineered to enable transport across the BBB. If the biologic does not cross the BBB, the drug cannot reach the target site in brain, and success in a clinical trial is not expected. Biologics can be re-engineered for BBB transport with the use of molecular Trojan horse technology. A BBB molecular Trojan horse is a monoclonal antibody (MAb) against an endogenous BBB receptor transporter, such as the insulin receptor or transferrin receptor. The receptor-specific MAb penetrates the brain via transport on the endogenous BBB receptor. The MAb acts as a molecular Trojan horse to deliver across the BBB the biologic pharmaceutical that is genetically fused to the MAb. The lead Trojan horse is a MAb against the human insulin receptor (HIR), and HIRMAb-derived fusion proteins have entered clinical trials for the treatment of brain disease.

  9. Combinatorial Approaches for the Identification of Brain Drug Delivery Targets

    Science.gov (United States)

    Stutz, Charles C.; Zhang, Xiaobin; Shusta, Eric V.

    2018-01-01

    The blood-brain barrier (BBB) represents a large obstacle for the treatment of central nervous system diseases. Targeting endogenous nutrient transporters that transcytose the BBB is one promising approach to selectively and noninvasively deliver a drug payload to the brain. The main limitations of the currently employed transcytosing receptors are their ubiquitous expression in the peripheral vasculature and the inherent low levels of transcytosis mediated by such systems. In this review, approaches designed to increase the repertoire of transcytosing receptors which can be targeted for the purpose of drug delivery are discussed. In particular, combinatorial protein libraries can be screened on BBB cells in vitro or in vivo to isolate targeting peptides or antibodies that can trigger transcytosis. Once these targeting reagents are discovered, the cognate BBB transcytosis system can be identified using techniques such as expression cloning or immunoprecipitation coupled with mass spectrometry. Continued technological advances in BBB genomics and proteomics, membrane protein manipulation, and in vitro BBB technology promise to further advance the capability to identify and optimize peptides and antibodies capable of mediating drug transport across the BBB. PMID:23789958

  10. On simulation of local fluxes in molecular junctions

    Science.gov (United States)

    Cabra, Gabriel; Jensen, Anders; Galperin, Michael

    2018-05-01

    We present a pedagogical review of the current density simulation in molecular junction models indicating its advantages and deficiencies in analysis of local junction transport characteristics. In particular, we argue that current density is a universal tool which provides more information than traditionally simulated bond currents, especially when discussing inelastic processes. However, current density simulations are sensitive to the choice of basis and electronic structure method. We note that while discussing the local current conservation in junctions, one has to account for the source term caused by the open character of the system and intra-molecular interactions. Our considerations are illustrated with numerical simulations of a benzenedithiol molecular junction.

  11. Soundscape of Urban Open Spaces in Hong Kong

    Science.gov (United States)

    Lin, Hui

    This study aims to investigate the soundscape of urban open spaces in Hong Kong. Open space in densely populated cities has been considered as an important asset for urban inhabitants in that they afford opportunities for leisure, recreation and an active involvement with nature. For quite a long time, visual aesthetic was the dominant consideration in open space design and other senses were given less concern. Continuous stream of attention-demanding sounds from the noisy environment may bombard these open spaces, rendering them no longer able to satisfy the eye alone. Sound and consequently the acoustic environment are receiving increasing attention. This study used noise mapping technique supplemented by GIS spatial analysis tools to delineate quiet open spaces with traffic noise exposure less than 60 dB (A) L10, 1h and conducted field observations to determine their usages. The identified quiet open spaces are either concentrated in hilly and remote areas with low accessibility, or sporadically scattered among tall buildings. Some large urban parks and small sitting-out areas are even located in the center of the city. Larger open spaces serve group visits, such as hiking and sightseeing, while smaller ones are easily accessible to local residents for social and recreational purposes. The acoustic environment III urban open spaces varies with space and time. To characterize the acoustic quality of soundscapes in the quiet open spaces, sound walk and field recording were undertaken place in 25 selected study sites. Despite the dominance of traffic noise, soundscapes in the urban open spaces are also shaped by natural sounds. Sounds from birds and water are common and prevalent particularly in gardens and playgrounds. Soundscape approach is a human-centered point of view. How the visitors perceive and evaluate sounds and the acoustic quality has great implication for soundscape design. On-site interview of 1,610 visitors unravels human preference of individual

  12. Fluorescein isothiocyanate (FITC)-Dextran Extravasation as a Measure of Blood-Brain Barrier Permeability

    Science.gov (United States)

    Natarajan, Reka; Northrop, Nicole

    2017-01-01

    The blood-brain barrier (BBB) is formed in part by vascular endothelial cells that constitute the capillaries and microvessels of the brain. The function of this barrier is to maintain homeostasis within the brain microenvironment and buffer the brain from changes in the periphery. A dysfunction of the BBB would permit circulating molecules and pathogens typically restricted to the periphery to enter the brain and interfere with normal brain function. As increased permeability of the BBB is associated with several neuropathologies, it is important to have a reliable and sensitive method that determines BBB permeability and the degree of BBB disruption. A detailed protocol is presented for assessing the integrity of the BBB by transcardial perfusion of a 10,000 Da FITC labeled dextran molecule and its visualization to determine the degree of extravasation from brain microvessels. PMID:28398646

  13. Quantitative targeted proteomics for understanding the blood-brain barrier: towards pharmacoproteomics.

    Science.gov (United States)

    Ohtsuki, Sumio; Hirayama, Mio; Ito, Shingo; Uchida, Yasuo; Tachikawa, Masanori; Terasaki, Tetsuya

    2014-06-01

    The blood-brain barrier (BBB) is formed by brain capillary endothelial cells linked together via complex tight junctions, and serves to prevent entry of drugs into the brain. Multiple transporters are expressed at the BBB, where they control exchange of materials between the circulating blood and brain interstitial fluid, thereby supporting and protecting the CNS. An understanding of the BBB is necessary for efficient development of CNS-acting drugs and to identify potential drug targets for treatment of CNS diseases. Quantitative targeted proteomics can provide detailed information on protein expression levels at the BBB. The present review highlights the latest applications of quantitative targeted proteomics in BBB research, specifically to evaluate species and in vivo-in vitro differences, and to reconstruct in vivo transport activity. Such a BBB quantitative proteomics approach can be considered as pharmacoproteomics.

  14. Adaption to extreme rainfall with open urban drainage system: an integrated hydrological cost-benefit analysis.

    Science.gov (United States)

    Zhou, Qianqian; Panduro, Toke Emil; Thorsen, Bo Jellesmark; Arnbjerg-Nielsen, Karsten

    2013-03-01

    This paper presents a cross-disciplinary framework for assessment of climate change adaptation to increased precipitation extremes considering pluvial flood risk as well as additional environmental services provided by some of the adaptation options. The ability of adaptation alternatives to cope with extreme rainfalls is evaluated using a quantitative flood risk approach based on urban inundation modeling and socio-economic analysis of corresponding costs and benefits. A hedonic valuation model is applied to capture the local economic gains or losses from more water bodies in green areas. The framework was applied to the northern part of the city of Aarhus, Denmark. We investigated four adaptation strategies that encompassed laissez-faire, larger sewer pipes, local infiltration units, and open drainage system in the urban green structure. We found that when taking into account environmental amenity effects, an integration of open drainage basins in urban recreational areas is likely the best adaptation strategy, followed by pipe enlargement and local infiltration strategies. All three were improvements compared to the fourth strategy of no measures taken.

  15. Open access

    NARCIS (Netherlands)

    Valkenburg, P.M.

    2015-01-01

    Open access week Van 19 tot en met 25 oktober 2015 vond wereldwijd de Open Access Week plaats. Tijdens deze week werden er over de hele wereld evenementen georganiseerd waar open access een rol speelt. Ook in Nederland zijn er diverse symposia, workshops en debatten georganiseerd zoals het debat in

  16. YouPower : An open source platform for community-oriented smart grid user engagement

    NARCIS (Netherlands)

    Huang, Yilin; Hasselqvist, Hanna; Poderi, Giacomo; Scepanovic, S.; Kis, F.; Bogdan, Cristian; Warnier, Martijn; Brazier, F.M.

    2017-01-01

    This paper presents YouPower, an open source platform designed to make people more aware of their energy consumption and encourage sustainable consumption with local communities. The platform is designed iteratively in collaboration with users in the Swedish and Italian test sites of the project

  17. OpenADR Open Source Toolkit: Developing Open Source Software for the Smart Grid

    Energy Technology Data Exchange (ETDEWEB)

    McParland, Charles

    2011-02-01

    Demand response (DR) is becoming an increasingly important part of power grid planning and operation. The advent of the Smart Grid, which mandates its use, further motivates selection and development of suitable software protocols to enable DR functionality. The OpenADR protocol has been developed and is being standardized to serve this goal. We believe that the development of a distributable, open source implementation of OpenADR will benefit this effort and motivate critical evaluation of its capabilities, by the wider community, for providing wide-scale DR services

  18. Towards OpenVL: Improving Real-Time Performance of Computer Vision Applications

    Science.gov (United States)

    Shen, Changsong; Little, James J.; Fels, Sidney

    Meeting constraints for real-time performance is a main issue for computer vision, especially for embedded computer vision systems. This chapter presents our progress on our open vision library (OpenVL), a novel software architecture to address efficiency through facilitating hardware acceleration, reusability, and scalability for computer vision systems. A logical image understanding pipeline is introduced to allow parallel processing. We also discuss progress on our middleware—vision library utility toolkit (VLUT)—that enables applications to operate transparently over a heterogeneous collection of hardware implementations. OpenVL works as a state machine,with an event-driven mechanismto provide users with application-level interaction. Various explicit or implicit synchronization and communication methods are supported among distributed processes in the logical pipelines. The intent of OpenVL is to allow users to quickly and easily recover useful information from multiple scenes, in a cross-platform, cross-language manner across various software environments and hardware platforms. To validate the critical underlying concepts of OpenVL, a human tracking system and a local positioning system are implemented and described. The novel architecture separates the specification of algorithmic details from the underlying implementation, allowing for different components to be implemented on an embedded system without recompiling code.

  19. Open areas and open access

    International Nuclear Information System (INIS)

    Thorndike, A.M.

    1979-01-01

    The main objective of the two open areas in the present ISABELLE design has been to provide flexibility with respect to the size and shape of experimental equipment that would eventually be installed there. No permanent building would be installed initially. One possibility would be to enclose each experiment in a temporary structure that would provide weatherproofing and shielding; another possibility would be to erect a permanent building at a later time, when experience has made the needs clearer than they are at present. The secondary objective of the design of open areas has been to keep initial costs as low as practicable. Another objective might be added, however, which we indicate by the term ''open access.'' This note will explore this idea and some design concepts based on it. In the ISABELLE 1977 summer workshop there was considerable discussion of the importance of techniques for inserting large pieces of experimental equipment quickly and removing them with equal ease and speed. Since enclosed halls have certain restrictions in this respect, open areas may be helpful in providing this feature. If the mechanical and electrical aspects could be handled quickly, one might even attempt to reduce the time spent on bureaucratic procedures in order to expedite the introduction of new experiments and new ideas in these areas

  20. Open Access @ DTU

    DEFF Research Database (Denmark)

    Ekstrøm, Jeannette

    Open Access is high on the agenda in Denmark and internationally. Denmark has announced a national strategy for Open Access that aims to achieve Open Access to 80% in 2017 and 100% in 2022 to peer review research articles. All public Danish funders as well as H2020 requires that all peer review...... articles that is an outcome of their funding will be Open Access. Uploading your full texts (your final author manuscript after review ) to DTU Orbit is a fundamental part of providing Open Access to your research. We are here to answer all your questions with regards to Open Access and related topics...... such as copyright, DTU Orbit, Open Access journals, APCs, Vouchers etc....

  1. Evaluation and selection of open-source EMR software packages based on integrated AHP and TOPSIS.

    Science.gov (United States)

    Zaidan, A A; Zaidan, B B; Al-Haiqi, Ahmed; Kiah, M L M; Hussain, Muzammil; Abdulnabi, Mohamed

    2015-02-01

    Evaluating and selecting software packages that meet the requirements of an organization are difficult aspects of software engineering process. Selecting the wrong open-source EMR software package can be costly and may adversely affect business processes and functioning of the organization. This study aims to evaluate and select open-source EMR software packages based on multi-criteria decision-making. A hands-on study was performed and a set of open-source EMR software packages were implemented locally on separate virtual machines to examine the systems more closely. Several measures as evaluation basis were specified, and the systems were selected based a set of metric outcomes using Integrated Analytic Hierarchy Process (AHP) and TOPSIS. The experimental results showed that GNUmed and OpenEMR software can provide better basis on ranking score records than other open-source EMR software packages. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Characterisation of an in vitro blood-brain barrier model based on primary porcine capillary endothelial cells in monoculture or co-culture with primary rat or porcine astrocytes and pericytes

    DEFF Research Database (Denmark)

    Thomsen, Louiza Bohn; Larsen, Annette Burkhart; Moos, Torben

    to in vivo such as efflux transporters, tight junction proteins, and high transendothelial electric resistance (TEER). Primary BCECs are isolated from a variety of mammals such as rats, mice, cattle and pigs. Often bovine and porcine BCECs are cultured in monoculture or in co-culture with rat astrocytes......In vitro blood-brain barrier (BBB) models based on primary brain capillary endothelial cells (BCECs) in monoculture or in co-culture with primary astrocytes and pericytes are often applied for studying physiology of the BBB. Primary BCECs retain many morphological and biochemical properties similar...... obtained from neonatal rats which have been shown to strengthen the barrier properties of the BCECs. In this study, brain endothelial cells (PBECs), astrocytes and pericytes are isolated from pig brains donated by the local abattoir. The brains are from 6 month old domestic pigs. The availability and high...

  3. Ammonia emission from organic pig houses determined with local parameters

    NARCIS (Netherlands)

    Aarnink, A.J.A.; Hol, J.M.G.; Ogink, N.W.M.

    2016-01-01

    The objective of this study was to determine the ammonia emissions from houses for growing-finishing pigs with an outside yard. While regular emission measurements are not possible in these open systems another approach was used. Local parameters were measured and used in an existing NH3 emission

  4. Risk analysis: opening the process

    International Nuclear Information System (INIS)

    Hubert, Ph.; Mays, C.

    1998-01-01

    This conference on risk analysis took place in Paris, 11-14 october 1999. Over 200 paper where presented in the seven following sessions: perception; environment and health; persuasive risks; objects and products; personal and collective involvement; assessment and valuation; management. A rational approach to risk analysis has been developed in the three last decades. Techniques for risk assessment have been thoroughly enhanced, risk management approaches have been developed, decision making processes have been clarified, the social dimensions of risk perception and management have been investigated. Nevertheless this construction is being challenged by recent events which reveal how deficits in stakeholder involvement, openness and democratic procedures can undermine risk management actions. Indeed, the global process most components of risk analysis may be radically called into question. Food safety has lately been a prominent issue, but now debates appear, or old debates are revisited in the domains of public health, consumer products safety, waste management, environmental risks, nuclear installations, automobile safety and pollution. To meet the growing pressures for efficiency, openness, accountability, and multi-partner communication in risk analysis, institutional changes are underway in many European countries. However, the need for stakeholders to develop better insight into the process may lead to an evolution of all the components of risks analysis, even in its most (technical' steps. For stakeholders of different professional background, political projects, and responsibilities, risk identification procedures must be rendered understandable, quantitative risk assessment must be intelligible and accommodated in action proposals, ranging from countermeasures to educational programs to insurance mechanisms. Management formats must be open to local and political input and other types of operational feedback. (authors)

  5. Can EPR non-locality be geometrical?

    International Nuclear Information System (INIS)

    Ne'eman, Y.

    1995-01-01

    The presence in Quantum Mechanics of non-local correlations is one of the two fundamentally non-intuitive features of that theory. The non-local correlations themselves fall into two classes: EPR and Geometrical. The non-local characteristics of the geometrical type are well-understood and are not suspected of possibly generating acausal features, such as faster-than-light propagation of information. This has especially become true since the emergence of a geometrical treatment for the relevant gauge theories, i.e. Fiber Bundle geometry, in which the quantum non-localities are seen to correspond to pure homotopy considerations. This aspect is reviewed in section 2. Contrary-wise, from its very conception, the EPR situation was felt to be paradoxical. It has been suggested that the non-local features of EPR might also derive from geometrical considerations, like all other non-local characteristics of QM. In[7], one of the authors was able to point out several plausibility arguments for this thesis, emphasizing in particular similarities between the non-local correlations provided by any gauge field theory and those required by the preservation of the quantum numbers of the original EPR state-vector, throughout its spatially-extended mode. The derivation was, however, somewhat incomplete, especially because of the apparent difference between, on the one hand, the closed spatial loops arising in the analysis of the geometrical non-localities, from Aharonov-Bohm and Berry phases to magnetic monopoles and instantons, and on the other hand, in the EPR case, the open line drawn by the positions of the two moving decay products of the disintegrating particle. In what follows, the authors endeavor to remove this obstacle and show that as in all other QM non-localities, EPR is somehow related to closed loops, almost involving homotopy considerations. They develop this view in section 3

  6. Glaucoma, Open-Angle

    Science.gov (United States)

    ... Home » Statistics and Data » Glaucoma, Open-angle Listen Glaucoma, Open-angle Open-angle Glaucoma Defined In open-angle glaucoma, the fluid passes ... 2010 2010 U.S. Age-Specific Prevalence Rates for Glaucoma by Age and Race/Ethnicity The prevalence of ...

  7. The Open Translation MOOC: Creating Online Communities to Transcend Linguistic Barriers

    Science.gov (United States)

    Beaven, Tita; Comas-Quinn, Anna; Hauck, Mirjam; de los Arcos, Beatriz; Lewis, Timothy

    2013-01-01

    One of the main barriers to the reuse of Open Educational Resources (OER) is language (OLnet, 2009). OER may be available but in a language that users cannot access, so a preliminary step to reuse is their translation or localization. One of the obvious solutions to the vast effort required to translate OER is to crowd-source the translation, as…

  8. Developing open source, self-contained disease surveillance software applications for use in resource-limited settings

    Directory of Open Access Journals (Sweden)

    Campbell Timothy C

    2012-09-01

    Full Text Available Abstract Background Emerging public health threats often originate in resource-limited countries. In recognition of this fact, the World Health Organization issued revised International Health Regulations in 2005, which call for significantly increased reporting and response capabilities for all signatory nations. Electronic biosurveillance systems can improve the timeliness of public health data collection, aid in the early detection of and response to disease outbreaks, and enhance situational awareness. Methods As components of its Suite for Automated Global bioSurveillance (SAGES program, The Johns Hopkins University Applied Physics Laboratory developed two open-source, electronic biosurveillance systems for use in resource-limited settings. OpenESSENCE provides web-based data entry, analysis, and reporting. ESSENCE Desktop Edition provides similar capabilities for settings without internet access. Both systems may be configured to collect data using locally available cell phone technologies. Results ESSENCE Desktop Edition has been deployed for two years in the Republic of the Philippines. Local health clinics have rapidly adopted the new technology to provide daily reporting, thus eliminating the two-to-three week data lag of the previous paper-based system. Conclusions OpenESSENCE and ESSENCE Desktop Edition are two open-source software products with the capability of significantly improving disease surveillance in a wide range of resource-limited settings. These products, and other emerging surveillance technologies, can assist resource-limited countries compliance with the revised International Health Regulations.

  9. Heterogeneous compute in computer vision: OpenCL in OpenCV

    Science.gov (United States)

    Gasparakis, Harris

    2014-02-01

    We explore the relevance of Heterogeneous System Architecture (HSA) in Computer Vision, both as a long term vision, and as a near term emerging reality via the recently ratified OpenCL 2.0 Khronos standard. After a brief review of OpenCL 1.2 and 2.0, including HSA features such as Shared Virtual Memory (SVM) and platform atomics, we identify what genres of Computer Vision workloads stand to benefit by leveraging those features, and we suggest a new mental framework that replaces GPU compute with hybrid HSA APU compute. As a case in point, we discuss, in some detail, popular object recognition algorithms (part-based models), emphasizing the interplay and concurrent collaboration between the GPU and CPU. We conclude by describing how OpenCL has been incorporated in OpenCV, a popular open source computer vision library, emphasizing recent work on the Transparent API, to appear in OpenCV 3.0, which unifies the native CPU and OpenCL execution paths under a single API, allowing the same code to execute either on CPU or on a OpenCL enabled device, without even recompiling.

  10. Intercomparison of open-path trace gas measurements with two dual-frequency-comb spectrometers

    Directory of Open Access Journals (Sweden)

    E. M. Waxman

    2017-09-01

    Full Text Available We present the first quantitative intercomparison between two open-path dual-comb spectroscopy (DCS instruments which were operated across adjacent 2 km open-air paths over a 2-week period. We used DCS to measure the atmospheric absorption spectrum in the near infrared from 6023 to 6376 cm−1 (1568 to 1660 nm, corresponding to a 355 cm−1 bandwidth, at 0.0067 cm−1 sample spacing. The measured absorption spectra agree with each other to within 5 × 10−4 in absorbance without any external calibration of either instrument. The absorption spectra are fit to retrieve path-integrated concentrations for carbon dioxide (CO2, methane (CH4, water (H2O, and deuterated water (HDO. The retrieved dry mole fractions agree to 0.14 % (0.57 ppm for CO2, 0.35 % (7 ppb for CH4, and 0.40 % (36 ppm for H2O at  ∼  30 s integration time over the 2-week measurement campaign, which included 24 °C outdoor temperature variations and periods of strong atmospheric turbulence. This agreement is at least an order of magnitude better than conventional active-source open-path instrument intercomparisons and is particularly relevant to future regional flux measurements as it allows accurate comparisons of open-path DCS data across locations and time. We additionally compare the open-path DCS retrievals to a World Meteorological Organization (WMO-calibrated cavity ring-down point sensor located along the path with good agreement. Short-term and long-term differences between the open-path DCS and point sensor are attributed, respectively, to spatial sampling discrepancies and to inaccuracies in the current spectral database used to fit the DCS data. Finally, the 2-week measurement campaign yields diurnal cycles of CO2 and CH4 that are consistent with the presence of local sources of CO2 and absence of local sources of CH4.

  11. PET imaging of TSPO in a rat model of local neuroinflammation induced by intracerebral injection of lipopolysaccharide

    International Nuclear Information System (INIS)

    Ory, Dieter; Planas, Anna; Dresselaers, Tom; Gsell, Willy; Postnov, Andrey; Celen, Sofie; Casteels, Cindy; Himmelreich, Uwe; Debyser, Zeger; Van Laere, Koen; Verbruggen, Alfons; Bormans, Guy

    2015-01-01

    Objective: The goal of this study was to measure functional and structural aspects of local neuroinflammation induced by intracerebral injection of lipopolysaccharide (LPS) in rats using TSPO microPET imaging with [ 18 F]DPA-714, magnetic resonance imaging (MRI), in vitro autoradiography and immunohistochemistry (IHC) in order to characterize a small animal model for screening of new PET tracers targeting neuroinflammation. Methods: Rats were injected stereotactically with LPS (50 μg) in the right striatum and with saline in the left striatum. [ 18 F]DPA-714 microPET, MRI, in vitro autoradiography and IHC studies were performed at different time points after LPS injection for 1 month. Results: Analysis of the microPET data demonstrated high uptake of the tracer in the LPS injected site with an affected-to-non-affected side-binding potential ratio (BP right-to-left ) of 3.0 at 3 days after LPS injection. This BP ratio decreased gradually over time to 0.9 at 30 days after LPS injection. In vitro autoradiography ([ 18 F]DPA-714) and IHC (CD68, GFAP and TSPO) confirmed local neuroinflammation in this model. Dynamic contrast enhanced (DCE) MRI demonstrated BBB breakdown near the LPS injection site at day 1, which gradually resolved over time and was absent at 1 month after LPS injection. Conclusion: The LPS model is useful for first screening of newly developed tracers because of the easy design and the robust, unilateral inflammatory reaction allowing the use of the contralateral region as control. Additionally, this model can be used to test and follow up the benefits of anti-inflammatory therapies by non-invasive imaging

  12. Transfection of brain capillary endothelial cells in primary culture with defined blood-brain barrier properties.

    Science.gov (United States)

    Burkhart, Annette; Thomsen, Louiza Bohn; Thomsen, Maj Schneider; Lichota, Jacek; Fazakas, Csilla; Krizbai, István; Moos, Torben

    2015-08-07

    Primary brain capillary endothelial cells (BCECs) are a promising tool to study the blood-brain barrier (BBB) in vitro, as they maintain many important characteristics of the BBB in vivo, especially when co-cultured with pericytes and/or astrocytes. A novel strategy for drug delivery to the brain is to transform BCECs into protein factories by genetic modifications leading to secretion of otherwise BBB impermeable proteins into the central nervous system. However, a huge challenge underlying this strategy is to enable transfection of non-mitotic BCECs, taking a non-viral approach. We therefore aimed to study transfection in primary, non-mitotic BCECs cultured with defined BBB properties without disrupting the cells' integrity. Primary cultures of BCECs, pericytes and astrocytes were generated from rat brains and used in three different in vitro BBB experimental arrangements, which were characterised based on a their expression of tight junction proteins and other BBB specific proteins, high trans-endothelial electrical resistance (TEER), and low passive permeability to radiolabeled mannitol. Recombinant gene expression and protein synthesis were examined in primary BCECs. The BCECs were transfected using a commercially available transfection agent Turbofect™ to express the red fluorescent protein HcRed1-C1. The BCECs were transfected at different time points to monitor transfection in relation to mitotic or non-mitotic cells, as indicated by fluorescence-activated cell sorting analysis after 5-and 6-carboxylfluorescein diacetate succinidyl ester incorporation. The cell cultures exhibited important BBB characteristics judged from their expression of BBB specific proteins, high TEER values, and low passive permeability. Among the three in vitro BBB models, co-culturing with BCECs and astrocytes was well suited for the transfection studies. Transfection was independent of cell division and with equal efficacy between the mitotic and non-mitotic BCECs. Importantly

  13. Model-based monitoring techniques for leakage localization in distribution water networks

    OpenAIRE

    Meseguer Amela, Jordi; Mirats Tur, Josep Maria; Cembrano Gennari, Gabriela; Puig Cayuela, Vicenç

    2015-01-01

    This is an open access article under the CC BY-NC-ND license This paper describes an integrated model-based monitoring framework for leakage localization in district-metered areas (DMA) of water distribution networks, which takes advantage of the availability of a hydraulic model of the network. The leakage localization methodology is based on the use of flow and pressure sensors at the DMA inlets and a limited number of pressure sensors deployed inside the DMA. The placement of these sens...

  14. Experimental Methods and Transport Models for Drug Delivery across the Blood-Brain Barrier

    OpenAIRE

    Fu, Bingmei M

    2012-01-01

    The blood-brain barrier (BBB) is a dynamic barrier essential for maintaining the micro-environment of the brain. Although the special anatomical features of the BBB determine its protective role for the central nervous system (CNS) from blood-born neurotoxins, however, the BBB extremely limits the therapeutic efficacy of drugs into the CNS, which greatly hinders the treatment of major brain diseases. This review summarized the unique structures of the BBB, described a variety of in vivo and i...

  15. The Blood-Brain Barrier: Connecting the Gut and the Brain

    OpenAIRE

    Banks, William A.

    2008-01-01

    The BBB prevents the unrestricted exchange of substances between the central nervous system (CNS) and the blood. The blood-brain barrier (BBB) also conveys information between the CNS and the gastrointestinal (GI) tract through several mechanisms. Here, we review three of those mechanisms. First, the BBB selectively transports some peptides and regulatory proteins in the blood-to-brain or the brain-to-blood direction. The ability of GI hormones to affect functions of the BBB, as illustrated b...

  16. CERN Open Days The LHC demystified!

    CERN Multimedia

    2008-01-01

    Lots of surprises are being planned for the CERN Open Days scheduled for 5 and 6 April (see 21 January edition of the Bulletin). Fred’s itinerary on 6 April 20089.00 a.m\tDeparture from SM12 at CERN (the pit down which all the LHC magnets were lowered into the tunnel)9.15 a.m. Saint-Genis theatre10.00 a.m.\tRoussillon communal hall in Crozet 10.50 a.m. La Chenaille communal hall in Echenevex 11.40 a.m. CMS Building SX5 at Cessy 2.30 p.m. La Forge communal hall in Versonnex 3.30 p.m. Le Levant communal hall in Ferney Voltaire4.40 Forum in Meyrin 5.30 p.m. Main Auditorium at CERN For instance, Fred, who fronts the French television programme "C’est pas sorcier" on France 3 will be taking part in the Open Day for the general public on Sunday, 6 April. He will be on board a CERN lorry carrying a 35 tonne 15 m long dipole magnet and will make halts at eight Swiss and French communes around the LHC Ring to meet the local inhabitants (see...

  17. Multispectral open-air intraoperative fluorescence imaging.

    Science.gov (United States)

    Behrooz, Ali; Waterman, Peter; Vasquez, Kristine O; Meganck, Jeff; Peterson, Jeffrey D; Faqir, Ilias; Kempner, Joshua

    2017-08-01

    Intraoperative fluorescence imaging informs decisions regarding surgical margins by detecting and localizing signals from fluorescent reporters, labeling targets such as malignant tissues. This guidance reduces the likelihood of undetected malignant tissue remaining after resection, eliminating the need for additional treatment or surgery. The primary challenges in performing open-air intraoperative fluorescence imaging come from the weak intensity of the fluorescence signal in the presence of strong surgical and ambient illumination, and the auto-fluorescence of non-target components, such as tissue, especially in the visible spectral window (400-650 nm). In this work, a multispectral open-air fluorescence imaging system is presented for translational image-guided intraoperative applications, which overcomes these challenges. The system is capable of imaging weak fluorescence signals with nanomolar sensitivity in the presence of surgical illumination. This is done using synchronized fluorescence excitation and image acquisition with real-time background subtraction. Additionally, the system uses a liquid crystal tunable filter for acquisition of multispectral images that are used to spectrally unmix target fluorescence from non-target auto-fluorescence. Results are validated by preclinical studies on murine models and translational canine oncology models.

  18. Modeling the ionosphere-thermosphere response to a geomagnetic storm using physics-based magnetospheric energy input: OpenGGCM-CTIM results

    Directory of Open Access Journals (Sweden)

    Connor Hyunju Kim

    2016-01-01

    Full Text Available The magnetosphere is a major source of energy for the Earth’s ionosphere and thermosphere (IT system. Current IT models drive the upper atmosphere using empirically calculated magnetospheric energy input. Thus, they do not sufficiently capture the storm-time dynamics, particularly at high latitudes. To improve the prediction capability of IT models, a physics-based magnetospheric input is necessary. Here, we use the Open Global General Circulation Model (OpenGGCM coupled with the Coupled Thermosphere Ionosphere Model (CTIM. OpenGGCM calculates a three-dimensional global magnetosphere and a two-dimensional high-latitude ionosphere by solving resistive magnetohydrodynamic (MHD equations with solar wind input. CTIM calculates a global thermosphere and a high-latitude ionosphere in three dimensions using realistic magnetospheric inputs from the OpenGGCM. We investigate whether the coupled model improves the storm-time IT responses by simulating a geomagnetic storm that is preceded by a strong solar wind pressure front on August 24, 2005. We compare the OpenGGCM-CTIM results with low-earth-orbit satellite observations and with the model results of Coupled Thermosphere-Ionosphere-Plasmasphere electrodynamics (CTIPe. CTIPe is an up-to-date version of CTIM that incorporates more IT dynamics such as a low-latitude ionosphere and a plasmasphere, but uses empirical magnetospheric input. OpenGGCM-CTIM reproduces localized neutral density peaks at ~ 400 km altitude in the high-latitude dayside regions in agreement with in situ observations during the pressure shock and the early phase of the storm. Although CTIPe is in some sense a much superior model than CTIM, it misses these localized enhancements. Unlike the CTIPe empirical input models, OpenGGCM-CTIM more faithfully produces localized increases of both auroral precipitation and ionospheric electric fields near the high-latitude dayside region after the pressure shock and after the storm onset

  19. Magnetic resonance imaging indicators of blood-brain barrier and brain water changes in young rats with kaolin-induced hydrocephalus.

    Science.gov (United States)

    Del Bigio, Marc R; Slobodian, Ili; Schellenberg, Angela E; Buist, Richard J; Kemp-Buors, Tanya L

    2011-08-11

    content in the immature rat model of hydrocephalus, probably because they are also influenced by other changes in tissue composition that occur during brain maturation. There is no evidence for widespread persistent opening of BBB as a consequence of hydrocephalus in young rats. However, increase in focal BBB permeability suggests that periventricular blood vessels may be disrupted.

  20. Magnetic resonance imaging indicators of blood-brain barrier and brain water changes in young rats with kaolin-induced hydrocephalus

    Directory of Open Access Journals (Sweden)

    Del Bigio Marc R

    2011-08-01

    characteristics cannot be used as direct surrogates for water content in the immature rat model of hydrocephalus, probably because they are also influenced by other changes in tissue composition that occur during brain maturation. There is no evidence for widespread persistent opening of BBB as a consequence of hydrocephalus in young rats. However, increase in focal BBB permeability suggests that periventricular blood vessels may be disrupted.

  1. L’iniziativa OpenDataNetwork, OpenData senza confini

    Directory of Open Access Journals (Sweden)

    Simone Giannechini

    2013-12-01

    Full Text Available In the last few years, the Open Data movement has made a significant impact on the IT world by bringing the att ention to an unexploited value represented by the tremendous amount of data that was kept hidden behind the gates of the existing infrastructures, both in public administrations and in private companies. This value can be declined in many ways depending on the perspective of the observer since unprecedented possibilities to correlate different sources of data to mine hidden trends and patt erns, can all at a sudden provide innovative ways to evaluate and monitor events and real life situation.After the initial period of the widespread adoption of the Open Data principles, we are now experimenting a situation where the amount of data available as Open Data is becoming overwhelming as such the need for some kind of coordinationeffort between different Open Data infrastructures is needed in order to make the data easier to browse and to exploit. This is the goal of the Open Data Network initiative. The Open Data Network initiative aim at bringing together a certain number ofItalian Public Administration with the goal of creating a standard infrastructure based on Open Source components suitable for the dissemination of data as Open Data. Moreover it aims at creating a network between each partner's node in order to ease the life of the end user as he will be allowed to access a central hub where all the information will be harvested, rather than having to deal with each single partner's infrastructure.

  2. Low mass planets in protoplanetary disks with net vertical magnetic fields: the Planetary Wake and Gap Opening

    OpenAIRE

    Zhu, Zhaohuan; Stone, James M.; Rafikov, Roman R.

    2013-01-01

    We study wakes and gap opening by low mass planets in gaseous protoplanetary disks threaded by net vertical magnetic fields which drive magnetohydrodynamical (MHD) turbulence through the magnetorotational instabilty (MRI), using three dimensional simulations in the unstratified local shearing box approximation. The wakes, which are excited by the planets, are damped by shocks similar to the wake damping in inviscid hydrodynamic (HD) disks. Angular momentum deposition by shock damping opens ga...

  3. RadNet: Open network protocol for radiation data

    International Nuclear Information System (INIS)

    Rees, B.; Olson, K.; Beckes-Talcott, J.; Kadner, S.; Wenderlich, T.; Hoy, M.; Doyle, W.; Koskelo, M.

    1998-01-01

    Safeguards instrumentation is increasingly being incorporated into remote monitoring applications. In the past, vendors of radiation monitoring instruments typically provided the tools for uploading the monitoring data to a host. However, the proprietary nature of communication protocols lends itself to increased computer support needs and increased installation expenses. As a result, a working group of suppliers and customers of radiation monitoring instruments defined an open network protocol for transferring packets on a local area network from radiation monitoring equipment to network hosts. The protocol was termed RadNet. While it is now primarily used for health physics instruments, RadNet's flexibility and strength make it ideal for remote monitoring of nuclear materials. The incorporation of standard, open protocols ensures that future work will not render present work obsolete; because RadNet utilizes standard Internet protocols, and is itself a non-proprietary standard. The use of industry standards also simplifies the development and implementation of ancillary services, e.g. E-main generation or even pager systems

  4. Open Source Opens Opportunities for Army's Simulation System

    National Research Council Canada - National Science Library

    Parsons, Douglas J; Wittman, Jr, Robert L

    2005-01-01

    .... Postured as an open-architecture, open-source application, the OneSAF program will put this software into the hands of a vast number of developers throughout the Department of Defense with the intent...

  5. Implementing OpenShift

    CERN Document Server

    Miller, Adam

    2013-01-01

    A standard tutorial-based approach to using OpenShift and deploying custom or pre-built web applications to the OpenShift Online cloud.This book is for software developers and DevOps alike who are interested in learning how to use the OpenShift Platform-as-a-Service for developing and deploying applications, how the environment works on the back end, and how to deploy their very own open source Platform-as-a-Service based on the upstream OpenShift Origin project.

  6. Researchers' perspectives on open access scholarly communication in Tanzanian public universities

    Directory of Open Access Journals (Sweden)

    F.W. Dulle

    2009-04-01

    Full Text Available This research explored the awareness, usage and perspectives of Tanzanian researchers on open access as a mode of scholarly communication. A survey questionnaire targeted 544 respondents selected through stratified random sampling from a population of 1088 university researchers of the six public universities in Tanzania. With a response rate of 73%, the data were analysed using the Statistical Package for Social Sciences. The study reveals that the majority of the researchers were aware of and were positive towards open access. Findings further indicate that the majority of researchers in Tanzanian public universities used open access outlets more to access scholarly content than to disseminate their own research findings. It seems that most of these researchers would support open access publishing more if issues of recognition, quality and ownership were resolved. Thus many of them supported the idea of establishing institutional repositories at their respective universities as a way of improving the dissemination of local content. The study recommends that public universities and other research institutions in the country should consider establishing institutional repositories, with appropriate quality assurance measures, to improve the dissemination of research output emanating from these institutions.

  7. Open-ended education

    DEFF Research Database (Denmark)

    Nørgård, Rikke Toft; Paaskesen, Rikke Berggreen

    2016-01-01

    THE ARTICLE DESCRIBES OPEN-ENDED EDUCATION FOR 21ST CENTURY LEARNING AS THE COMING TOGETHER OF OPEN-ENDED TECHNOLOGY, OPEN-ENDED PROJECTS, AND OPEN-ENDED INSTITUTIONS IN WAYS THAT FOSTER AND PROMOTE FUTURE EDUCATION FOR CITIZENSHIP IN SOCIETY. THROUGH THE CASE OF THE CODING PIRATES FUTURE ISLAND......, THE ARTICLE DEMONSTRATES HOW OPEN-ENDED EDUCATION CAN BE PRACTICED TO FOSTER AND PROMOTE TECHNOLOGICAL IMAGINATION, ENTERPRISING, AND PARTICIPATION. THIS PRACTICE IS THEN DEVELOPED INTO A THEORETICAL MODEL FOR THE CONCEPT OF OPEN-ENDED EDUCATION AS A WAY OF AND FRAMEWORK FOR PRACTICING FUTURE EDUCATION FOR 21......ST CENTURY LEARNING WITH NEW TECHNOLOGIES. THE ARTICLE PRESENTS AN ANSWER TO THE CALL FOR 21ST CENTURY LEARNING AS THOROUGHLY COLLABORATIVE, COMMUNICATIVE, CREATIVE, AND CRITICALLY REFLECTIVE THROUGH THE CASE AND THE CONCEPT OF OPEN-ENDED EDUCATION. IT OUTLINES THE IMPLICATIONS OF THIS CALL...

  8. Cerebral amyloid angiopathy, blood-brain barrier disruption and amyloid accumulation in SAMP8 mice.

    Science.gov (United States)

    del Valle, Jaume; Duran-Vilaregut, Joaquim; Manich, Gemma; Pallàs, Mercè; Camins, Antoni; Vilaplana, Jordi; Pelegrí, Carme

    2011-01-01

    Cerebrovascular dysfunction and β-amyloid peptide deposition on the walls of cerebral blood vessels might be an early event in the development of Alzheimer's disease. Here we studied the time course of amyloid deposition in blood vessels and blood-brain barrier (BBB) disruption in the CA1 subzone of the hippocampus of SAMP8 mice and the association between these two variables. We also studied the association between the amyloid deposition in blood vessels and the recently described amyloid clusters in the parenchyma, as well as the association of these clusters with vessels in which the BBB is disrupted. SAMP8 mice showed greater amyloid deposition in blood vessels than age-matched ICR-CD1 control mice. Moreover, at 12 months of age the number of vessels with a disrupted BBB had increased in both strains, especially SAMP8 animals. At this age, all the vessels with amyloid deposition showed BBB disruption, but several capillaries with an altered BBB showed no amyloid on their walls. Moreover, amyloid clusters showed no spatial association with vessels with amyloid deposition, nor with vessels in which the BBB had been disrupted. Finally, we can conclude that vascular amyloid deposition seems to induce BBB alterations, but BBB disruption may also be due to other factors. Copyright © 2011 S. Karger AG, Basel.

  9. Interrelations between blood-brain barrier permeability and matrix metalloproteinases are differently affected by tissue plasminogen activator and hyperoxia in a rat model of embolic stroke

    Directory of Open Access Journals (Sweden)

    Michalski Dominik

    2012-01-01

    Full Text Available Abstract Background In ischemic stroke, blood-brain barrier (BBB regulations, typically involving matrix metalloproteinases (MMPs and inhibitors (TIMPs as mediators, became interesting since tissue plasminogen activator (tPA-related BBB breakdown with risk of secondary hemorrhage was considered to involve these mediators too. Despite high clinical relevance, detailed interactions are purely understood. After a pilot study addressing hyperoxia as potential neuroprotective co-treatment to tPA, we analyzed interrelations between BBB permeability (BBB-P, MMPs and TIMPs. Findings Rats underwent embolic middle cerebral artery occlusion (eMCAO and treatment with normobaric (NBO or hyperbaric oxygen (HBO, tPA, tPA+HBO, or no treatment. BBB-P was assessed by intravenously applied FITC-albumin at 4 or 24 hours. MMP-2/-9 and TIMP-1/-2 serum levels were determined at 5 or 25 hours. Time point-corrected partial correlations were used to explore interrelations of BBB-P in ischemic regions (extra-/intravasal FITC-albumin ratio and related serum markers. BBB-P correlated positively with MMP-2 and MMP-9 in controls, whereas hyperoxia led to an inverse association, most pronounced for HBO/MMP-9 (r = -0.606; P Conclusions HBO was found to reverse the positively directed interrelation of BBB-P and MMPs after eMCAO, but this effect failed to sustain in the expected amount when HBO and tPA were given simultaneously.

  10. A Simple and Reproducible Method to Prepare Membrane Samples from Freshly Isolated Rat Brain Microvessels.

    Science.gov (United States)

    Brzica, Hrvoje; Abdullahi, Wazir; Reilly, Bianca G; Ronaldson, Patrick T

    2018-05-07

    The blood-brain barrier (BBB) is a dynamic barrier tissue that responds to various pathophysiological and pharmacological stimuli. Such changes resulting from these stimuli can greatly modulate drug delivery to the brain and, by extension, cause considerable challenges in the treatment of central nervous system (CNS) diseases. Many BBB changes that affect pharmacotherapy, involve proteins that are localized and expressed at the level of endothelial cells. Indeed, such knowledge on BBB physiology in health and disease has sparked considerable interest in the study of these membrane proteins. From a basic science research standpoint, this implies a requirement for a simple but robust and reproducible method for isolation of microvessels from brain tissue harvested from experimental animals. In order to prepare membrane samples from freshly isolated microvessels, it is essential that sample preparations be enriched in endothelial cells but limited in the presence of other cell types of the neurovascular unit (i.e., astrocytes, microglia, neurons, pericytes). An added benefit is the ability to prepare samples from individual animals in order to capture the true variability of protein expression in an experimental population. In this manuscript, details regarding a method that is utilized for isolation of rat brain microvessels and preparation of membrane samples are provided. Microvessel enrichment, from samples derived, is achieved by using four centrifugation steps where dextran is included in the sample buffer. This protocol can easily be adapted by other laboratories for their own specific applications. Samples generated from this protocol have been shown to yield robust experimental data from protein analysis experiments that can greatly aid the understanding of BBB responses to physiological, pathophysiological, and pharmacological stimuli.

  11. The Open Method of Coordination and the Implementation of the Bologna Process

    Science.gov (United States)

    Veiga, Amelia; Amaral, Alberto

    2006-01-01

    In this paper the authors argue that the use of the Open Method of Coordination (OMC) in the implementation of the Bologna process presents coordination problems that do not allow for the full coherence of the results. As the process is quite complex, involving three different levels (European, national and local) and as the final actors in the…

  12. Context-Aware Browsing for Hyper-Local News Data (CABHLND

    Directory of Open Access Journals (Sweden)

    Dr. Yousef Ibrahim Daradkeh

    2012-07-01

    Full Text Available This paper describes a new model for delivering hyper-local data to mobile subscribers. Our model uses any exiting or especially created Wi-Fi hot spot as presence sensor that can open access for some user-generated content. In our approach we can describe hyper local data as info snippets that are valid (relevant for mobile subscribers being at this moment nearby some Wi-Fi access point. And an appropriate mobile service (customized browser can discover that information to mobile users. Service builds on the fly dynamic web pages and lets mobile subscribers to browse hyper-local data only. As the possible use-cases we can mention for example delivering news and deals in malls, news feeds for office centers and campuses, Smart City projects, personal classifieds etc.

  13. Move the Neighborhood: study design of a community-based participatory public open space intervention

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Winge, Laura; Carroll, Sidse

    evaluation will be used to gain knowledge of the intervention processes. DISCUSSION: The study presents new methods and approaches in the field of public open space interventions through interdisciplinary collaboration, participatory co-design approach and combination of measurements. Using both effect......BACKGROUND: A limited amount of research has examined the effect of changing public open spaces on active living. This abstract presents the study protocol of an intervention study designed in an interdisciplinary collaboration built on principles of Community-Based Participatory Research (CBPR...... and process evaluations the study will provide unique insights in the role and importance of the interdisciplinary collaboration, participatory processes, tailoring changes in public open space to local needs and wishes. These results can be used to guide urban renewal projects in deprived neighbourhoods...

  14. Family Open House

    Science.gov (United States)

    Search Family Open House Join us for an afternoon of science fun. The Fermilab Family Open House is a party for children of all ages to learn about the world of physics. The Open House is supported by Open House? Check out our YouTube video to learn more! Explore physics concepts with hands-on

  15. Loopholes in Bell inequality tests of local realism

    International Nuclear Information System (INIS)

    Larsson, Jan-Åke

    2014-01-01

    Bell inequalities are intended to show that local realist theories cannot describe the world. A local realist theory is one where physical properties are defined prior to and independent of measurement, and no physical influence can propagate faster than the speed of light. Quantum-mechanical predictions for certain experiments violate the Bell inequality while a local realist theory cannot, and this shows that a local realist theory cannot give those quantum-mechanical predictions. However, because of unexpected circumstances or ‘loopholes’ in available experiment tests, local realist theories can reproduce the data from these experiments. This paper reviews such loopholes, what effect they have on Bell inequality tests, and how to avoid them in experiment. Avoiding all these simultaneously in one experiment, usually called a ‘loophole-free’ or ‘definitive’ Bell test, remains an open task, but is very important for technological tasks such as device-independent security of quantum cryptography, and ultimately for our understanding of the world. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘50 years of Bell’s theorem’. (review article)

  16. Toward Appropriate Missiology for Post-Soviet Evangelicals: Global Missiological Trends and Local Realities

    OpenAIRE

    CHERENKOV, Michael

    2011-01-01

    The future of missions in post-Soviet countries is tied to the formation/development of an appropriate, indigenous, authentic, effective, comprehensive missiological paradigm, which is based on Biblical principles, opens up into a holistic theoretical system, synthesizes the historical experience of churches and various theological approaches, takes into account the local context, and is oriented towards the needs and issues of local communities. Each of these requirements is presented as nec...

  17. On the Anderson localization conjecture in Dusty Plasma

    Science.gov (United States)

    Liaw, Constanze; Busse, Kyle; Matthews, Lorin; Hyde, Truell

    2015-11-01

    In 1958, Anderson suggested that sufficiently large impurities in a semi-conductor could lead to spatial localization of electrons. This idea unfolded into the field of Anderson Localization, one of the most fascinating phenomena in solid-state physics as it plays a major role in the conductive properties of imperfectly ordered materials. The Anderson Localization Conjecture claims that random disorder of any strength causes localization of electrons in the medium. The problem has proven to be highly non-trivial. Over the years the community has argued whether spatial localization occurs in 2D for small impurities. From a mathematical standpoint, the conjecture is still considered an open question. In 2013, Liaw challenged the commonly held assumption that localization holds in 2D by introducing a new mathematically more rigorous method to test for extended states, and applying it to the discrete random Schrödinger operator. One of the advantages of the underlying method is its versatility. It can be applied to any ordered system such as colloids, crystals, and atomic lattices. In a cross-disciplinary effort we merge this method with a numerical code used to simulate 2D physics systems, in preparation for experimentally testing the theory against complex plasma crystals.

  18. TNAP and EHD1 are over-expressed in bovine brain capillary endothelial cells after the re-induction of blood-brain barrier properties.

    Directory of Open Access Journals (Sweden)

    Barbara Deracinois

    Full Text Available Although the physiological properties of the blood-brain barrier (BBB are relatively well known, the phenotype of the component brain capillary endothelial cells (BCECs has yet to be described in detail. Likewise, the molecular mechanisms that govern the establishment and maintenance of the BBB are largely unknown. Proteomics can be used to assess quantitative changes in protein levels and identify proteins involved in the molecular pathways responsible for cellular differentiation. Using the well-established in vitro BBB model developed in our laboratory, we performed a differential nano-LC MALDI-TOF/TOF-MS study of Triton X-100-soluble protein species from bovine BCECs displaying either limited BBB functions or BBB functions re-induced by glial cells. Due to the heterogeneity of the crude extract, we increased identification yields by applying a repeatable, reproducible fractionation process based on the proteins' relative hydrophobicity. We present proteomic and biochemical evidence to show that tissue non-specific alkaline phosphatase (TNAP and Eps15 homology domain-containing protein 1(EDH1 are over-expressed by bovine BCECs after the re-induction of BBB properties. We discuss the impact of these findings on current knowledge of endothelial and BBB permeability.

  19. Advanced design of local ventilation systems

    Energy Technology Data Exchange (ETDEWEB)

    Kulmala, I. [VTT Manufacturing Technology, Espoo (Finland). Safety Technology

    1997-12-31

    Local ventilation is widely used in industry for controlling airborne contaminants. However, the present design practices of local ventilation systems are mainly based on empirical equations and do not take quantitatively into account the various factors affecting the performance of these systems. The aim of this study was to determine the applicability and limitations of more advanced fluid mechanical methods to the design and development of local ventilation systems. The most important factors affecting the performance of local ventilation systems were determined and their effect was studied in a systematic manner. The numerical calculations were made with the FLUENT computer code and they were verified by laboratory experiments, previous measurements or analytical solutions. The results proved that the numerical calculations can provide a realistic simulation of exhaust openings, effects of ambient air flows and wake regions. The experiences with the low-velocity local supply air showed that these systems can also be modelled fairly well. The results were used to improve the efficiency and thermal comfort of a local ventilation unit and to increase the effective control range of exhaust hoods. In the simulation of the interaction of a hot buoyant source and local exhaust, the predicted capture efficiencies were clearly higher than those observed experimentally. The deviations between measurements and non-isothermal flow calculations may have partly been caused by the inability to achieve grid independent solutions. CFD simulations is an advanced and flexible tool for designing and developing local ventilation. The simulations can provide insight into the time-averaged flow field which may assist us in understanding the observed phenomena and to explain experimental results. However, for successful calculations the applicability and limitations of the models must be known. (orig.) 78 refs.

  20. An open ecosystem engagement strategy through the lens of global food safety [v1; ref status: indexed, http://f1000r.es/527