How Acute and Chronic Alcohol Consumption Affects Brain Networks: Insights from Multimodal Neuroimaging

Background— Multimodal imaging combining 2 or more techniques is becoming increasingly important because no single imaging approach has the capacity to elucidate all clinically relevant characteristics of a network. Methods— This review highlights recent advances in multimodal neuroimaging (i.e., combined use and interpretation of data collected through magnetic resonance imaging [MRI], functional MRI, diffusion tensor imaging, positron emission tomography, magnetoencephalography, MR perfusion, and MR spectroscopy methods) that leads to a more comprehensive understanding of how acute and chronic alcohol consumption affect neural networks underlying cognition, emotion, reward processing, and drinking behavior. Results— Several innovative investigators have started utilizing multiple imaging approaches within the same individual to better understand how alcohol influences brain systems, both during intoxication and after years of chronic heavy use. Conclusions— Their findings can help identify mechanism-based therapeutic and pharmacological treatment options, and they may increase the efficacy and cost effectiveness of such treatments by predicting those at greatest risk for relapse

A zone melting device for the in situ observation of directional solidification using high-energy synchrotron x rays editors-pick

Directional solidification (DS) is an established manufacturing process to produce high-performance components from metallic materials with optimized properties. Materials for demanding high-temperature applications, for instance in the energy generation and aircraft engine technology, can only be successfully produced using methods such as directional solidification. It has been applied on an industrial scale for a considerable amount of time, but advancing this method beyond the current applications is still challenging and almost exclusively limited to post-process characterization of the developed microstructures. For a knowledge-based advancement and a contribution to material innovation, in situ studies of the DS process are crucial using realistic sample sizes to ensure scalability of the results to industrial sizes. Therefore, a specially designed Flexible Directional Solidification (FlexiDS) device was developed for use at the P07 High Energy Materials Science beamline at PETRA III (Deutsches Elektronen–Synchrotron, Hamburg, Germany). In general, the process conditions of the crucible-free, inductively heated FlexiDS device can be varied from 6 mm/h to 12 000 mm/h (vertical withdrawal rate) and from 0 rpm to 35 rpm (axial sample rotation). Moreover, different atmospheres such as Ar, N2, and vacuum can be used during operation. The device is designed for maximum operation temperatures of 2200 °C. This unique device allows in situ examination of the directional solidification process and subsequent solid-state reactions by x-ray diffraction in the transmission mode. Within this project, different structural intermetallic alloys with liquidus temperatures up to 2000 °C were studied in terms of liquid–solid regions, transformations, and decompositions, with varying process conditions

Assessment of the Al–Fe–Ti system

The Al–Fe–Ti system has been assessed and the limiting binary systems are shortly reviewed. Based on a thorough review of the literature, isotherms at 800, 900, and 1000 °C have been re-evaluated and a provisional isotherm at 1200 °C is presented for the first time. The effect of alloying the binary phases with the third component is reviewed with regard to the ternary homogeneity ranges, crystallography, order/disorder transformations, and site occupancies. Of the variously reported ternary compounds only the existence of “Al2FeTi” (τ2) and “Al8FeTi3” (τ3) is confirmed. The occurrence of the phases τ2*, τ′2, and of a new stacking variant of TiAl is still under discussion, while the existence of the phases Fe2AlTi (τ1) and Fe25Al69Ti6 (X) is ruled out. The presented reaction scheme corroborates the isothermal sections and also a representation of the liquidus surface is given. Magnetic, electrical, thermochemical, atomistic and diffusion data for Al–Fe–Ti alloys are summarised and an overview about studies on modelling of phase equilibria and phase transformations is given

Genetic variations in VEGF and VEGFR2 and glioblastoma outcome

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) are central components in the development and progression of glioblastoma. To investigate if genetic variation in VEGF and VEGFR2 is associated with glioblastoma prognosis, we examined blood samples from 154 glioblastoma cases collected in Sweden and Denmark between 2000 and 2004. Seventeen tagging single nucleotide polymorphisms (SNPs) in VEGF and 27 in VEGFR2 were genotyped and analysed, covering 90% of the genetic variability within the genes. In VEGF, we found no SNPs associated with survival. In VEGFR2, we found two SNPs significantly associated to survival, namely rs2071559 and rs12502008. However, these results are likely to be false positives due to multiple testing and could not be confirmed in a separate dataset. Overall, this study provides little evidence that VEGF and VEGFR2 polymorphisms are important for glioblastoma survival

Age-related differences in selection by visual saliency

We examined the ability of older adults to select local and global stimuli varying in perceptual saliency – a task requiring non-spatial visual selection. Participants were asked to identify in separate blocks a target at either the global or local level of a hierarchical stimulus, while the saliency of each level was varied (across different conditions either the local or the global form was the more salient and relatively easier to identify). Older adults were less efficient than young adults in ignoring distractors that were higher in saliency than targets, and this occurred across both the global and local levels of form. The increased effects of distractor saliency on older adults occurred even when the effects were scaled by overall differences in task performance. The data provide evidence for an age-related decline in non spatial attentional selection of low-salient hierarchical stimuli, not determined by the (global or local) level at which selection was required. We discuss the implications of these results for understanding both the interaction between saliency and hierarchical processing and the effects of aging on non-spatial visual attention

Nuclear Factor-Kappa B Family Member RelB Inhibits Human Immunodeficiency Virus-1 Tat-Induced Tumor Necrosis Factor-Alpha Production

Human Immunodeficiency Virus-1 (HIV-1)-associated neurocognitive disorder (HAND) is likely neuroinflammatory in origin, believed to be triggered by inflammatory and oxidative stress responses to cytokines and HIV protein gene products such as the HIV transactivator of transcription (Tat). Here we demonstrate increased messenger RNA for nuclear factor-kappa B (NF-κB) family member, transcription factor RelB, in the brain of doxycycline-induced Tat transgenic mice, and increased RelB synthesis in Tat-exposed microglial cells. Since genetic ablation of RelB in mice leads to multi-organ inflammation, we hypothesized that Tat-induced, newly synthesized RelB inhibits cytokine production by microglial cells, possibly through the formation of transcriptionally inactive RelB/RelA complexes. Indeed, tumor necrosis factor-alpha (TNFα) production in monocytes isolated from RelB deficient mice was significantly higher than in monocytes isolated from RelB expressing controls. Moreover, RelB overexpression in microglial cells inhibited Tat-induced TNFα synthesis in a manner that involved transcriptional repression of the TNFα promoter, and increased phosphorylation of RelA at serine 276, a prerequisite for increased RelB/RelA protein interactions. The Rel-homology-domain within RelB was necessary for this interaction. Overexpression of RelA itself, in turn, significantly increased TNFα promoter activity, an effect that was completely blocked by RelB overexpression. We conclude that RelB regulates TNFα cytokine synthesis by competitive interference binding with RelA, which leads to downregulation of TNFα production. Moreover, because Tat activates both RelB and TNFα in microglia, and because Tat induces inflammatory TNFα synthesis via NF-κB, we posit that RelB serves as a cryoprotective, anti-inflammatory, counter-regulatory mechanism for pathogenic NF-κB activation. These findings identify a novel regulatory pathway for controlling HIV-induced microglial activation and cytokine production that may have important therapeutic implications for the management of HAND

FIM-ATOM PROBE STUDIES OF THE DECOMPOSITION IN THE METALLIC GLASS Ni45 Pd35 P20

A Field Ion Microscope (FIM) combined with an Atom Probe (AP) was used to study decomposition in the metallic glass Ni45 Pd35 P20. As-quenched specimens are found to be homogeneous whereas isothermally annealed specimens show phosphorous enrichment of small concentration amplitudes and diameters. Two glass temperatures are observed in annealed specimens. The temper embrittlement in this glass must be caused by crystallisation, not by decomposition