946 research outputs found

    Tetragonal CuO: A new end member of the 3d transition metal monoxides

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    Monoclinic CuO is anomalous both structurally as well as electronically in the 3dd transition metal oxide series. All the others have the cubic rock salt structure. Here we report the synthesis and electronic property determination of a tetragonal (elongated rock salt) form of CuO created using an epitaxial thin film deposition approach. In situ photoelectron spectroscopy suggests an enhanced charge transfer gap Δ\Delta with the overall bonding more ionic. As an end member of the 3d transition monoxides, its magnetic properties should be that of a high TNT_N antiferromagnet

    Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia

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    HIV-1-associated dementia remains a common subacute to chronic central nervous system degeneration in adult and pediatric HIV-1 infected populations. A number of viral and host factors have been implicated including the HIV-1 120 kDa envelope glycoprotein (gp120). In human post-mortem studies using confocal scanning laser microscopy for microtubule-associated protein 2 and synaptophysin, neuronal dendritic pathology correlated with dementia. In the present study, primary human CNS cultures exposed to HIV-1 gp120 at 4 weeks in vitro suffered gliosis and dendritic damage analogous to that described in association with HIV-1-associated dementia

    Maternal Undernourishment in Guinea Pigs Leads to Fetal Growth Restriction with Increased Hypoxic Cells and Oxidative Stress in the Brain.

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    BACKGROUND: We determined whether maternal nutrient restriction (MNR) in guinea pigs leading to fetal growth restriction (FGR) impacts markers for brain hypoxia and oxidative stress. METHODS: Guinea pigs were fed ad libitum (control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Near term, hypoxyprobe-1 (HP-1) was injected into pregnant sows. Fetuses were then necropsied and brain tissues were processed for HP-1 (hypoxia marker) and 4HNE, 8-OHdG, and 3-nitrotyrosine (oxidative stress markers) immunoreactivity (IR). RESULTS: FGR-MNR fetal and brain weights were decreased 38 and 12%, respectively, with brain/fetal weights thereby increased 45% as a measure of brain sparing, and more so in males than females. FGR-MNR HP-1 IR was increased in most of the brain regions studied, and more so in males than females, while 4HNE and 8-OHdG IR were increased in select brain regions, but with no sex differences. CONCLUSIONS: Chronic hypoxia is likely to be an important signaling mechanism in the FGR brain, but with males showing more hypoxia than females. This may involve sex differences in adaptive decreases in growth and normalizing of oxygen, with implications for sex-specific alterations in brain development and risk for later neuropsychiatric disorder

    Supreme Court Brief Amicus Curiae of Administrative Law Scholars in Support of Neither Party

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    This brief on behalf of 29 administrative law scholars takes no position on whether Administrative Law Judges (ALJs) are employees or inferior officers. It urges the Court to issue an opinion that respects the decision that Congress made unanimously in 1946 to enact numerous statutory safeguards that assure that ALJs have decisional independence from the agencies where they work while assuring that agencies retain control over the policy content and legal basis for any decision made in an adjudication in which an ALJ presides. The brief describes the fifteen years of study and deliberation that led to the unanimous decision of Congress to enact the Administrative Procedure Act (APA) in 1946. It describes the particular attention that Congress devoted to the critical task of providing ALJs with the combination of statutory safeguards that minimize the risk that they will favor the agencies for whom they adjudicate cases while assuring that the agencies retain control of the policy content of any decision made in such an adjudication. It then describes the series of opinions the Supreme Court issued during the 1950s in which the Justices unanimously praised the provisions of the APA that assure that ALJs conduct adjudicatory hearings in an unbiased manner, explained the importance of those statutory provisions in protecting the values reflected in the Due Process Clause, and urged Congress to make those safeguards applicable to all agency adjudications. It concludes by urging the Court to issue an opinion that respects the decision that Congress made in 1946 to insulate ALJs from potential sources of pro-agency bias by including in the APA a combination of provisions that confer decisional independence on ALJs

    Quantitative relaxometry and diffusion MRI for lateralization in MTS and non-MTS temporal lobe epilepsy.

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    We developed novel methodology for investigating the use of quantitative relaxometry (T1 and T2) and diffusion tensor imaging (DTI) for lateralization in temporal lobe epilepsy. Patients with mesial temporal sclerosis confirmed by pathology (N=8) and non-MTS unilateral temporal lobe epilepsy (N=6) were compared against healthy controls (N=19) using voxel-based analysis restricted to the anterior temporal lobes, and laterality indices for each MRI metric (T1, T2, fractional anisotropy (FA), mean diffusivity, axial and radial diffusivities) were computed based on the proportion of significant voxels on each side. The diffusivity metrics were the most lateralizing MRI metrics in MTS and non-MTS subsets, with significant differences also seen with FA, T1 and T2. Patient-specific multi-modal laterality indices were also computed and were shown to clearly separate the left-onset and right-onset patients. Marked differences between left-onset and right-onset patients were also observed, with left-onset patients exhibiting stronger laterality indices. Finally, neocortical abnormalities were found to be more common in the non-MTS patients. These preliminary results on a small sample size support the further investigation of quantitative MRI and multi-modal image analysis in clinical determination of seizure onset. The presence of more neocortical abnormalities in the non-MTS group suggests a role in seizure onset or propagation and motivates the investigation of more sensitive histopathological analysis to detect and delineate potentially subtle neocortical pathology

    Antioxidant protection from HIV-1 gp120-induced neuroglial toxicity

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    BACKGROUND: The pathogenesis of HIV-1 glycoprotein 120 (gp120) associated neuroglial toxicity remains unresolved, but oxidative injury has been widely implicated as a contributing factor. In previous studies, exposure of primary human central nervous system tissue cultures to gp120 led to a simplification of neuronal dendritic elements as well as astrocytic hypertrophy and hyperplasia; neuropathological features of HIV-1-associated dementia. Gp120 and proinflammatory cytokines upregulate inducible nitric oxide synthase (iNOS), an important source of nitric oxide (NO) and nitrosative stress. Because ascorbate scavenges reactive nitrogen and oxygen species, we studied the effect of ascorbate supplementation on iNOS expression as well as the neuronal and glial structural changes associated with gp120 exposure. METHODS: Human CNS cultures were derived from 16–18 week gestation post-mortem fetal brain. Cultures were incubated with 400 μM ascorbate-2-O-phosphate (Asc-p) or vehicle for 18 hours then exposed to 1 nM gp120 for 24 hours. The expression of iNOS and neuronal (MAP2) and astrocytic (GFAP) structural proteins was examined by immunohistochemistry and immunofluorescence using confocal scanning laser microscopy (CSLM). RESULTS: Following gp120 exposure iNOS was markedly upregulated from undetectable levels at baseline. Double label CSLM studies revealed astrocytes to be the prime source of iNOS with rare neurons expressing iNOS. This upregulation was attenuated by the preincubation with Asc-p, which raised the intracellular concentration of ascorbate. Astrocytic hypertrophy and neuronal injury caused by gp120 were also prevented by preincubation with ascorbate. CONCLUSIONS: Ascorbate supplementation prevents the deleterious upregulation of iNOS and associated neuronal and astrocytic protein expression and structural changes caused by gp120 in human brain cell cultures

    Registration of in-vivo to ex-vivo MRI of surgically resected specimens: A pipeline for histology to in-vivo registration.

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    BACKGROUND: Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to develop and evaluate a protocol for deformable image registration of in-vivo to ex-vivo resected brain specimen MRI. This protocol, in conjunction with our previous work on ex-vivo to histology registration, completes a registration pipeline for histology to in-vivo MRI, enabling voxel-based validation of novel and existing MRI techniques with histopathology. NEW METHOD: A combination of image-based and landmark-based 3D registration was used to register in-vivo MRI and the ex-vivo MRI from patients (N=10) undergoing epilepsy surgery. Target registration error (TRE) was used to assess accuracy and the added benefit of deformable registration. RESULTS: A mean TRE of 1.35±0.11 and 1.41±0.33mm was found for neocortical and hippocampal specimens respectively. Statistical analysis confirmed that the deformable registration significantly improved the registration accuracy for both specimens. COMPARISON WITH EXISTING METHODS: Image registration of surgically resected brain specimens is a unique application which presents numerous technical challenges and that have not been fully addressed in previous literature. Our computed TRE are comparable to previous attempts tackling similar applications, as registering in-vivo MRI to whole brain or serial histology. CONCLUSION: The presented registration pipeline finds dense and accurate spatial correspondence between in-vivo MRI and histology and allows for the spatially local and quantitative assessment of pathological correlates in MRI

    Magnetic resonance imaging and histology correlation in the neocortex in temporal lobe epilepsy.

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    OBJECTIVE: To investigate the histopathological correlates of quantitative relaxometry and diffusion tensor imaging (DTI) and to determine their efficacy in epileptogenic lesion detection for preoperative evaluation of focal epilepsy. METHODS: We correlated quantitative relaxometry and DTI with histological features of neuronal density and morphology in 55 regions of the temporal lobe neocortex, selected from 13 patients who underwent epilepsy surgery. We made use of a validated nonrigid image registration protocol to obtain accurate correspondences between in vivo magnetic resonance imaging and histology images. RESULTS: We found T1 to be a predictor of neuronal density in the neocortical gray matter (GM) using linear mixed effects models with random effects for subjects. Fractional anisotropy (FA) was a predictor of neuronal density of large-caliber neurons only (pyramidal cells, layers 3 and 5). Comparing multivariate to univariate mixed effects models with nested variables demonstrated that employing T1 and FA together provided a significantly better fit than T1 or FA alone in predicting density of large-caliber neurons. Correlations with clinical variables revealed significant positive correlations between neuronal density and age (rs  = 0.726, pfwe  = 0.021). This study is the first to relate in vivo T1 and FA values to the proportion of neurons in GM. INTERPRETATION: Our results suggest that quantitative T1 mapping and DTI may have a role in preoperative evaluation of focal epilepsy and can be extended to identify GM pathology in a variety of neurological disorders
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