155 research outputs found

    Thermal patterning of superconducting films

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    Includes bibliographical references (page 600).The transient shape control of a superconducting high Tc film by selective optical heating has been addressed in this work, using a non-conventional technique that combines the application of a pulsed magnetic field and the optical heating of the superconducting film by a synchronized pulsed laser. A zero field cooled (ZFC) film was partially protected by a mask before exposing it to the laser radiation. The temperature at the illuminated area rises causing very fast local lowering of the vortex pinning force or may even rise above Tc. As a result, flux penetrates completely the heated area and an effective smaller sample remains in a superconducting critical state. Flux penetration is measured with a pick-up coil for different positions of the mask. Results are described within the critical state model for a strip, where the time integrated voltage signal is approximated to the flux difference between the initial ZFC sample and the final critical state of the "new" (cold) ZFC sample

    Altered metabolic profiles associate with toxicity in SOD1G93A astrocyte-neuron co-cultures

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    Non-cell autonomous processes involving astrocytes have been shown to contribute to motor neuron degeneration in amyotrophic lateral sclerosis. Mutant superoxide dismutase 1 (SOD1G93A) expression in astrocytes is selectively toxic to motor neurons in co-culture, even when mutant protein is expressed only in astrocytes and not in neurons. To examine metabolic changes in astrocyte-spinal neuron co-cultures, we carried out metabolomic analysis by 1H NMR spectroscopy of media from astrocyte-spinal neuron co-cultures and astrocyte-only cultures. We observed increased glucose uptake with SOD1G93A expression in all co-cultures, but while co-cultures with only SOD1G93A neurons had lower extracellular lactate, those with only SOD1G93A astrocytes exhibited the reverse. Reduced branched-chain amino acid uptake and increased accumulation of 3-methyl-2-oxovalerate were observed in co-culture with only SOD1G93A neurons while glutamate was reduced in all co-cultures expressing SOD1G93A. The shifts in these coupled processes suggest a potential block in glutamate processing that may impact motor neuron survival. We also observed metabolic alterations which may relate to oxidative stress responses. Overall, the different metabolite changes observed with the two SOD1G93A cell types highlight the role of the astrocyte-motor neuron interaction in the resulting metabolic phenotype, requiring further examination of altered metabolic pathways and their impact on motor neuron survival

    Spinal cord metabolic signatures in models of fast- and slow-progressing SOD1G93A Amyotrophic Lateral Sclerosis

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    The rate of disease progression in amyotrophic lateral sclerosis (ALS) is highly variable, even between patients with the same genetic mutations. Metabolic alterations may affect disease course variability in ALS patients, but challenges in identifying the preclinical and early phases of the disease limit our understanding of molecular mechanisms underlying differences in the rate of disease progression. We examined effects of SOD1G93A on thoracic and lumbar spinal cord metabolites in two mouse ALS models with different rates of disease progression: the transgenic SOD1G93A-C57BL/6JOlaHsd (C57-G93A, slow progression) and transgenic SOD1G93A-129SvHsd (129S-G93A, fast progression) strains. Samples from three timepoints (presymptomatic, disease onset, and late stage disease) were analyzed using Gas Chromatography-Mass Spectrometry metabolomics. Tissue metabolome differences in the lumbar spinal cord were driven primarily by mouse genetic background, although larger responses were observed in metabolic trajectories after the onset of symptoms. The significantly affected lumbar spinal cord metabolites were involved in energy and lipid metabolism. In the thoracic spinal cord, metabolic differences related to genetic background, background-SOD1 genotype interactions, and longitudinal SOD1G93A effects. The largest responses in thoracic spinal cord metabolic trajectories related to SOD1G93A effects before onset of visible symptoms. More metabolites were significantly affected in the thoracic segment, which were involved in energy homeostasis, neurotransmitter synthesis and utilization, and the oxidative stress response. We find evidence that initial metabolic alterations in SOD1G93A mice confer disadvantages for maintaining neuronal viability under ALS-related stressors, with slow-progressing C57-G93A mice potentially having more favorable spinal cord bioenergetic profiles than 129S-G93A. These genetic background-associated metabolic differences together with the different early metabolic responses underscore the need to better characterize the impact of germline genetic variation on cellular responses to ALS gene mutations both before and after the onset of symptoms in order to understand their impact on disease development

    Fourier ring correlation simplifies image restoration in fluorescence microscopy

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    Fourier ring correlation (FRC) has recently gained popularity among fluorescence microscopists as a straightforward and objective method to measure the effective image resolution. While the knowledge of the numeric resolution value is helpful in e.g., interpreting imaging results, much more practical use can be made of FRC analysis\u2014in this article we propose blind image restoration methods enabled by it. We apply FRC to perform image de-noising by frequency domain filtering. We propose novel blind linear and non-linear image deconvolution methods that use FRC to estimate the effective point-spread-function, directly from the images. We show how FRC can be used as a powerful metric to observe the progress of iterative deconvolution. We also address two important limitations in FRC that may be of more general interest: how to make FRC work with single images (within certain practical limits) and with three-dimensional images with highly anisotropic resolution

    Efecto del uso de media sombra y manta anti helada en lechuga (Lactuca sativa) de invierno

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    Lettuce is considered the most consumed vegetable in the country which grows throughout the year. The aim of this work was to evaluate the effect of the shading net and floating row covers on the yield and leaf appearance in winter lettuce. The trial was carried out in EEA INTA Colonia Benítez, Chaco on Argiudol oxic soil. The crop was cultivated under three different conditions, 50% shade net, floating row covers and in open sky. The sowing date was on 06/06/2012 using the cv. Grand Rapid and distances of 0.40 m between rows and 0.25 m between plants. The harvesting and yield determination were at 77 DAS. In each situation, soil temperature and PAR were measured.  The results showed the highest yields in open sky, followed by floating row covers and the lowest yield in shadde net 50%. The average PAR was higher in open sky conditions, followed by floating row covers and 50% shade net, while  soil temperature showed values within the optimal range for cultivation in the three treatments being higher in the floating row covers one. These results evidenced that the use of 50% shade net reduced the yield in winter conditions in Colonia Benítez (Chaco),  which was not the case of floating row covers.La lechuga se caracteriza por ser una de las principales hortalizas consumidas en el país y por cultivarse durante todo el año. El objetivo del trabajo fue evaluar el efecto de la media sombra y manta anti helada sobre el rendimiento y aparición de hojas en un cultivo de lechuga invernal. El ensayo se realizó en la EEA INTA Colonia Benítez, Chaco sobre un suelo clasificado como Argiudol óxico. El cultivo se realizó bajo tres condiciones diferentes, media sombra 50%, manta anti helada y a cielo abierto. La siembra de lechuga se realizó el 06/06/2012 utilizándose el cv. Grand Rapid y distancias de 0,40 m entre líneos y de 0,25 entre plantas. A los 77 DDS se procedió a la cosecha y determinación del rendimiento. En cada situación de cultivo se midió temperatura de suelo y radiación PAR. Los resultados mostraron los mayores rendimientos en el cultivo a cielo abierto, seguido por manta anti helada y el menor rendimiento bajo media sombra 50%. La media de la radiación PAR fue superior en condiciones de cielo abierto, seguido por manta anti helada y media sombra 50%, por su parte la temperatura de suelo mostró valores dentro del rango óptimo para el cultivo en los tres tratamientos siendo mayor en el tratamiento manta anti helada. Estos resultados evidencian que para las condiciones de invierno en Colonia Benítez (Chaco) el uso de media sombra al 50% disminuyó el rendimiento, no así con el uso de manta anti helada

    Multiple intracerebroventricular injections of human umbilical cord mesenchymal stem cells delay motor neurons loss but not disease progression of SOD1G93A mice

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    Stem cell therapy is considered a promising approach in the treatment of amyotrophic lateral sclerosis (ALS) and mesenchymal stem cells (MSCs) seem to be the most effective in ALS animal models. The umbilical cord (UC) is a source of highly proliferating fetal MSCs, more easily collectable than other MSCs. Recently we demonstrated that human (h) UC-MSCs, double labeled with fluorescent nanoparticles and Hoechst-33258 and transplanted intracerebroventricularly (ICV) into SOD1G93A transgenic mice, partially migrated into the spinal cord after a single injection. This prompted us to assess the effect of repeated ICV injections of hUC-MSCs on disease progression in SOD1G93A mice. Although no transplanted cells migrated to the spinal cord, a partial but significant protection of motor neurons (MNs) was found in the lumbar spinal cord of hUC-MSCs-treated SOD1G93A mice, accompanied by a shift from a pro-inflammatory (IL-6, IL-1\u3b2) to anti-inflammatory (IL-4, IL-10) and neuroprotective (IGF-1) environment in the lumbar spinal cord, probably linked to the activation of p-Akt survival pathway in both motor neurons and reactive astrocytes. However, this treatment neither prevented the muscle denervation nor delayed the disease progression of mice, emphasizing the growing evidence that protecting the motor neuron perikarya is not sufficient to delay the ALS progression

    RNS60 exerts therapeutic effects in the SOD1 ALS mouse model through protective glia and peripheral nerve rescue

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    Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects the motor neuromuscular system leading to complete paralysis and premature death. The multifactorial nature of ALS that involves both cell-autonomous and non-cell-autonomous processes contributes to the lack of effective therapies, usually targeted to a single pathogenic mechanism. RNS60, an experimental drug containing oxygenated nanobubbles generated by modified Taylor-Couette-Poiseuille flow with elevated oxygen pressure, has shown anti-inflammatory and neuroprotective properties in different experimental paradigms. Since RNS60 interferes with multiple cellular mechanisms known to be involved in ALS pathology, we evaluated its effect in in vitro and in vivo models of ALS. Methods: Co-cultures of primary microglia/spinal neurons exposed to LPS and astrocytes/spinal neurons from SOD1 G93A mice were used to examine the effect of RNS60 or normal saline (NS) on the selective motor neuron degeneration. Transgenic SOD1 G93A mice were treated with RNS60 or NS (300\u3bcl/mouse intraperitoneally every other day) starting at the disease onset and examined for disease progression as well as pathological and biochemical alterations. Results: RNS60 protected motor neurons in in vitro paradigms and slowed the disease progression of C57BL/6-SOD1 G93A mice through a significant protection of spinal motor neurons and neuromuscular junctions. This was mediated by the (i) activation of an antioxidant response and generation of an anti-inflammatory environment in the spinal cord; (ii) activation of the PI3K-Akt pro-survival pathway in the spinal cord and sciatic nerves; (iii) reduced demyelination of the sciatic nerves; and (iv) elevation of peripheral CD4+/Foxp3+ T regulatory cell numbers. RNS60 did not show the same effects in 129Sv-SOD1 G93A mice, which are unable to activate a protective immune response. Conclusion: RNS60 demonstrated significant therapeutic efficacy in C57BL/6-SOD1 G93A mice by virtue of its effects on multiple disease mechanisms in motor neurons, glial cells, and peripheral immune cells. These findings, together with the excellent clinical safety profile, make RNS60 a promising candidate for ALS therapy and support further studies to unravel its molecular mechanism of action. In addition, the differences in efficacy of RNS60 in SOD1 G93A mice of different strains may be relevant for identifying potential markers to predict efficacy in clinical trials

    Irreversible transformation of ferromagnetic ordered stripe domains in single-shot IR pump - resonant X-ray scattering probe experiments

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    The evolution of a magnetic domain structure upon excitation by an intense, femtosecond Infra-Red (IR) laser pulse has been investigated using single-shot based time-resolved resonant X-ray scattering at the X-ray Free Electron laser LCLS. A well-ordered stripe domain pattern as present in a thin CoPd alloy film has been used as prototype magnetic domain structure for this study. The fluence of the IR laser pump pulse was sufficient to lead to an almost complete quenching of the magnetization within the ultrafast demagnetization process taking place within the first few hundreds of femtoseconds following the IR laser pump pulse excitation. On longer time scales this excitation gave rise to subsequent irreversible transformations of the magnetic domain structure. Under our specific experimental conditions, it took about 2 nanoseconds before the magnetization started to recover. After about 5 nanoseconds the previously ordered stripe domain structure had evolved into a disordered labyrinth domain structure. Surprisingly, we observe after about 7 nanoseconds the occurrence of a partially ordered stripe domain structure reoriented into a novel direction. It is this domain structure in which the sample's magnetization stabilizes as revealed by scattering patterns recorded long after the initial pump-probe cycle. Using micro-magnetic simulations we can explain this observation based on changes of the magnetic anisotropy going along with heat dissipation in the film.Comment: 16 pages, 6 figure

    Talampanel reduces the level of motoneuronal calcium in transgenic mutant SOD1 mice only if applied presymptomatically

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    We tested the efficacy of treatment with talampanel in a mutant SOD1 mouse model of ALS by measuring intracellular calcium levels and loss of spinal motor neurons. We intended to mimic the clinical study; hence, treatment was started when the clinical symptoms were already present. The data were compared with the results of similar treatment started at a presymptomatic stage. Transgenic and wild-type mice were treated either with talampanel or with vehicle, starting in pre-symptomatic or symptomatic stages. The density of motor neurons was determined by the physical disector, and their intracellular calcium level was assayed electron microscopically. Results showed that motor neurons in the SOD1 mice exhibited an elevated calcium level, which could be reduced, but not restored, with talampanel only when the treatment was started presymptomatically. Treatment in either presymptomatic or symptomatic stages failed to rescue the motor neurons. We conclude that talampanel reduces motoneuronal calcium in a mouse model of ALS, but its efficacy declines as the disease progresses, suggesting that medication initiation in the earlier stages of the disease might be more effective
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