Flowing gas, non-nuclear experiments on the gas core reactor

Flow tests were conducted on models of the gas core (cavity) reactor. Variations in cavity wall and injection configurations were aimed at establishing flow patterns that give a maximum of the nuclear criticality eigenvalue. Correlation with the nuclear effect was made using multigroup diffusion theory normalized by previous benchmark critical experiments. Air was used to simulate the hydrogen propellant in the flow tests, and smoked air, argon, or freon to simulate the central nuclear fuel gas. All tests were run in the down-firing direction so that gravitational effects simulated the acceleration effect of a rocket. Results show that acceptable flow patterns with high volume fraction for the simulated nuclear fuel gas and high flow rate ratios of propellant to fuel can be obtained. Using a point injector for the fuel, good flow patterns are obtained by directing the outer gas at high velocity along the cavity wall, using louvered or oblique-angle-honeycomb injection schemes

Connectome analysis for pre-operative brain mapping in neurosurgery.

OBJECT: Brain mapping has entered a new era focusing on complex network connectivity. Central to this is the search for the connectome or the brains 'wiring diagram'. Graph theory analysis of the connectome allows understanding of the importance of regions to network function, and the consequences of their impairment or excision. Our goal was to apply connectome analysis in patients with brain tumours to characterise overall network topology and individual patterns of connectivity alterations. METHODS: Resting-state functional MRI data were acquired using multi-echo, echo planar imaging pre-operatively from five participants each with a right temporal-parietal-occipital glioblastoma. Complex networks analysis was initiated by parcellating the brain into anatomically regions amongst which connections were identified by retaining the most significant correlations between the respective wavelet decomposed time-series. RESULTS: Key characteristics of complex networks described in healthy controls were preserved in these patients, including ubiquitous small world organization. An exponentially truncated power law fit to the degree distribution predicted findings of general network robustness to injury but with a core of hubs exhibiting disproportionate vulnerability. Tumours produced a consistent reduction in local and long-range connectivity with distinct patterns of connection loss depending on lesion location. CONCLUSIONS: Connectome analysis is a feasible and novel approach to brain mapping in individual patients with brain tumours. Applications to pre-surgical planning include identifying regions critical to network function that should be preserved and visualising connections at risk from tumour resection. In the future one could use such data to model functional plasticity and recovery of cognitive deficits.S. J. P. received funding for this study through a National Institute for Health Research (NIHR) (UK) – Clinician Scientist Award (Ref: NIHR/CS/009/011). M. G. H. is funded by the Wellcome Trust Neuroscience in Psychiatry Network with additional support from the National Institute for Health Research Cambridge Biomedical Research Centre. This paper presents independent research funded by the NIHR.This is the final version of the article. It first appeared from Taylor & Francis via http://dx.doi.org/10.1080/02688697.2016.120880

Global Effects of Focal Brain Tumors on Functional Complexity and Network Robustness: A Prospective Cohort Study.

BACKGROUND: Neurosurgical management of brain tumors has entered a paradigm of supramarginal resections that demands thorough understanding of peritumoral functional effects. Historically, the effects of tumors have been believed to be local, and long-range effects have not been considered. OBJECTIVE: To test the hypothesis that tumors affect the brain globally, producing long-range gradients in cortical function. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were acquired from 11 participants with glioblastoma and split into discovery and validation datasets in a single-center prospective cohort study. Fractal complexity was computed with a wavelet-based estimator of the Hurst exponent. Distance-related effects of the tumors were tested with a tumor mask-dilation technique and parcellation of the underlying Hurst maps. RESULTS: Fractal complexity demonstrates a penumbra of suppression in the peritumoral region. At a global level, as distance from the tumor increases, this initial suppression is balanced by a subsequent overactivity before finally normalizing. These effects were best fit by a quadratic model and were consistent across different network construction pipelines. The Hurst exponent was correlated with graph theory measures of centrality including network robustness, but graph theory measures did not demonstrate distance-dependent effects. CONCLUSION: This work provides evidence supporting the theory that focal brain tumors produce long-range gradients in function. Consequently, the effects of focal lesions need to be interpreted in terms of the global changes on functional complexity and network architecture rather than purely in terms of functional localization. Determining whether peritumoral changes represent potential plasticity may facilitate extended resection of tumors without functional cost.MGH is funded by the Wellcome Trust Neuroscience in Psychiatry Network with additional support from the National Institute for Health Research Cambridge Biomedical Research Centre. The imaging studies were funded by an NIHR Clinician Scientist Fellowship for SJP (NIHR/CS/009/011)

A detailed binding free energy study of 2 : 1 ligand–DNA complex formation by experiment and simulation

In 2004, we used NMR to solve the structure of the minor groove binder thiazotropsin A bound in a 2 : 1 complex to the DNA duplex, d(CGACTAGTCG)2. In this current work, we have combined theory and experiment to confirm the binding thermodynamics of this system. Molecular dynamics simulations that use polarizable or non-polarizable force fields with single and separate trajectory approaches have been used to explore complexation at the molecular level. We have shown that the binding process invokes large conformational changes in both the receptor and ligand, which is reflected by large adaptation energies. This is compensated for by the net binding free energy, which is enthalpy driven and entropically opposed. Such a conformational change upon binding directly impacts on how the process must be simulated in order to yield accurate results. Our MM-PBSA binding calculations from snapshots obtained from MD simulations of the polarizable force field using separate trajectories yield an absolute binding free energy (-15.4 kcal mol-1) very close to that determined by isothermal titration calorimetry (-10.2 kcal mol-1). Analysis of the major energy components reveals that favorable non-bonded van der Waals and electrostatic interactions contribute predominantly to the enthalpy term, whilst the unfavorable entropy appears to be driven by stabilization of the complex and the associated loss of conformational freedom. Our results have led to a deeper understanding of the nature of side-by-side minor groove ligand binding, which has significant implications for structure-based ligand development

Probiotic Supplementation and Gastrointestinal Endotoxemia Before and After the Marathon Des Sables.

Whilst evidence of increased gastrointestinal endotoxemia (GE) has been previously demonstrated during single-day ultra-endurance events, less is known on the prevalence of GE following extreme ultra-events such as the Marathon Des Sables (MDS). The potential benefit of probiotic formulas on gut integrity during ultra-endurance events also requires further investigation. PURPOSE: To assess the impact of probiotic supplementation with or without glutamine on GE prevalence in runners competing in a multi-day ultra-run (MDS). METHODS: Thirty four healthy participants from the 2015 MDS UK cohort volunteered for a 12 week pre-race intervention and were randomly assigned to either: probiotic (PRO; 100mg.d-1 lactobacillus acidophilus) (age 40 ±3 yrs., weight 79.4 ±2.0kg, VO2max 4.2 ±0.1 L.min-1), probiotic with glutamine (PROglut; 40.5mg.d-1 lactobacillus acidophilus and 900mg.d-1L-glutamine) (age 39 ±2 yrs., weight 70.6 ±4.8 kg, VO2max 4.0 ±0.2 L.min-1) and control (CON) (age 42±3 yrs., weight 79.2 ±3.8 kg, VO2max 4.0 ±0.3 L.min-1). Plasma lipopolysaccharides (LPS) (via Limulus Amebocyte Lysate chromogenic endotoxin quantification) were assessed at weeks 0, 12, post-race and 7 days post-race. Performance data was collated from official timing chips. Data presented as mean ±SE. RESULTS: Mild to moderate GE was prevalent in all groups at baseline (PRO 9.71 ±0.85pg.ml-1, PROglut 9.89 ±1.43 pg.ml-1, CON 9.40 ±0.57 pg.ml-1; P>0.05). Whilst LPS, post intervention, was lower in PROglut there was no significance between groups (9.81 ±1.47pg.ml-1 vs 12.80 ±0.93pg.ml-1 (PRO) vs 11.72 ±1.08 pg.mol-1 (CON); P>0.05). LPS were evidently reduced 6hrs post-race, but not different between groups (PRO: 7.29 ±1.41 pg.ml-1, PROglut: 6.95 ±0.94 pg.ml-1, CON: 9.73 ±1.39 pg.ml-1; P>0.05).Plasma LPS returned to baseline levels 7 days post-race (PRO 7.60 ±0.95 pg.ml-1, PROglut 10.41 ±1.04 pg.ml-1, CON 8.57 ±0.75 pg.ml-1; P>0.05). Race performance (hrs:mins) was not significant between groups, despite PRO and PROglut being ~9hrs faster than CON (41:28±2:31 vs 41:58±4:02 vs 50:43±4:38; P>0.05). CONCLUSION: Moderate GE was prevalent in all groups pre-race and fell significantly during the short-term recovery period. Despite promising results neither probiotic formula had a significant impact on GE or race performance

The effect of long term physical training in the development of mental toughness in recreationally active participants

This study investigated the effect of a long-term training program on the development of mental toughness (MT). Thirty (2 female and 28 male) recreationally active participants (age: 33.53±6.83years; height: 177.41±7.11cm; weight: 78.40±11.94kg; maximal oxygen uptake (VO2max): 47.00±6.48 ml.kg-1.min-1; mean±SD) undertook 6 months of training prior to completing a long-distance triathlon. Participants completed mental toughness questionnaires (MTQ48) at 0, 2, 4, and 6 months of training and 1-month post-race. Data analysis included repeated measures ANOVAs for each MTQ48 variable with consideration to faster and slower finishers. Faster and slower finishers demonstrated non-significant differences (p>0.05) on all MT criteria. There was an effect for time with overall mental toughness (OMT) improving from baseline-post race (cohens d = 0.52; p<0.01) and month 2 post race (d = 0.39; p<0.01), commitment improving from baseline-post race (d = 0.60; p<0.05) and confidence increasing from month 2 post race (d = 0.39; p<0.05). The findings indicate that long term training culminating with competitive experience favourably impacts MT

Lesion covariance networks reveal proposed origins and pathways of diffuse gliomas.

Diffuse gliomas have been hypothesized to originate from neural stem cells in the subventricular zone and develop along previously healthy brain networks. Here, we evaluated these hypotheses by mapping independent sources of glioma localization and determining their relationships with neurogenic niches, genetic markers and large-scale connectivity networks. By applying independent component analysis to lesion data from 242 adult patients with high- and low-grade glioma, we identified three lesion covariance networks, which reflect clusters of frequent glioma localization. Replicability of the lesion covariance networks was assessed in an independent sample of 168 glioma patients. We related the lesion covariance networks to important clinical variables, including tumour grade and patient survival, as well as genomic information such as molecular genetic subtype and bulk transcriptomic profiles. Finally, we systematically cross-correlated the lesion covariance networks with structural and functional connectivity networks derived from neuroimaging data of over 4000 healthy UK BioBank participants to uncover intrinsic brain networks that may that underlie tumour development. The three lesion covariance networks overlapped with the anterior, posterior and inferior horns of the lateral ventricles respectively, extending into the frontal, parietal and temporal cortices. These locations were independently replicated. The first lesion covariance network, which overlapped with the anterior horn, was associated with low-grade, isocitrate dehydrogenase -mutated/1p19q-codeleted tumours, as well as a neural transcriptomic signature and improved overall survival. Each lesion covariance network significantly coincided with multiple structural and functional connectivity networks, with the first bearing an especially strong relationship with brain connectivity, consistent with its neural transcriptomic profile. Finally, we identified subcortical, periventricular structures with functional connectivity patterns to the cortex that significantly matched each lesion covariance network. In conclusion, we demonstrated replicable patterns of glioma localization with clinical relevance and spatial correspondence with large-scale functional and structural connectivity networks. These results are consistent with prior reports of glioma growth along white matter pathways, as well as evidence for the coordination of glioma stem cell proliferation by neuronal activity. Our findings describe how the locations of gliomas relate to their proposed subventricular origins, suggesting a model wherein periventricular brain connectivity guides tumour development

Lesion covariance networks reveal proposed origins and pathways of diffuse gliomas.

Diffuse gliomas have been hypothesized to originate from neural stem cells in the subventricular zone and develop along previously healthy brain networks. Here, we evaluated these hypotheses by mapping independent sources of glioma localization and determining their relationships with neurogenic niches, genetic markers and large-scale connectivity networks. By applying independent component analysis to lesion data from 242 adult patients with high- and low-grade glioma, we identified three lesion covariance networks, which reflect clusters of frequent glioma localization. Replicability of the lesion covariance networks was assessed in an independent sample of 168 glioma patients. We related the lesion covariance networks to important clinical variables, including tumour grade and patient survival, as well as genomic information such as molecular genetic subtype and bulk transcriptomic profiles. Finally, we systematically cross-correlated the lesion covariance networks with structural and functional connectivity networks derived from neuroimaging data of over 4000 healthy UK BioBank participants to uncover intrinsic brain networks that may that underlie tumour development. The three lesion covariance networks overlapped with the anterior, posterior and inferior horns of the lateral ventricles respectively, extending into the frontal, parietal and temporal cortices. These locations were independently replicated. The first lesion covariance network, which overlapped with the anterior horn, was associated with low-grade, isocitrate dehydrogenase -mutated/1p19q-codeleted tumours, as well as a neural transcriptomic signature and improved overall survival. Each lesion covariance network significantly coincided with multiple structural and functional connectivity networks, with the first bearing an especially strong relationship with brain connectivity, consistent with its neural transcriptomic profile. Finally, we identified subcortical, periventricular structures with functional connectivity patterns to the cortex that significantly matched each lesion covariance network. In conclusion, we demonstrated replicable patterns of glioma localization with clinical relevance and spatial correspondence with large-scale functional and structural connectivity networks. These results are consistent with prior reports of glioma growth along white matter pathways, as well as evidence for the coordination of glioma stem cell proliferation by neuronal activity. Our findings describe how the locations of gliomas relate to their proposed subventricular origins, suggesting a model wherein periventricular brain connectivity guides tumour development

BOLD Coupling between Lesioned and Healthy Brain Is Associated with Glioma Patients’ Recovery

Predicting functional outcomes after surgery and early adjuvant treatment is difficult due to the complex, extended, interlocking brain networks that underpin cognition. The aim of this study was to test glioma functional interactions with the rest of the brain, thereby identifying the risk factors of cognitive recovery or deterioration. Seventeen patients with diffuse non-enhancing glioma (aged 22–56 years) were longitudinally MRI scanned and cognitively assessed before and after surgery and during a 12-month recovery period (55 MRI scans in total after exclusions). We initially found, and then replicated in an independent dataset, that the spatial correlation pattern between regional and global BOLD signals (also known as global signal topography) was associated with tumour occurrence. We then estimated the coupling between the BOLD signal from within the tumour and the signal extracted from different brain tissues. We observed that the normative global signal topography is reorganised in glioma patients during the recovery period. Moreover, we found that the BOLD signal within the tumour and lesioned brain was coupled with the global signal and that this coupling was associated with cognitive recovery. Nevertheless, patients did not show any apparent disruption of functional connectivity within canonical functional networks. Understanding how tumour infiltration and coupling are related to patients’ recovery represents a major step forward in prognostic development.Consejeria de Economia, Innovacion, Ciencia y Empleo.Junta de Andalucia CV20-45250; A-TIC-080-UGR18; B-TIC-586-UGR20; P20-0052

Liquid baits with Oenococcus oeni increase captures of Drosophila suzukii

The spotted-wing drosophila (SWD), Drosophila suzukii Matsumura (Diptera: Drosophilidae), native to Eastern Asia, is an invasive alien species in Europe and the Americas, where it is a severe pest of horticultural crops, including soft fruits and wine grapes. The conventional approach to controlling infestations of SWD involves the use of insecticides, but the frequency of application for population management is undesirable. Consequently, alternative strategies are urgently needed. Effective and improved trapping is important as an early risk detection tool. This study aimed to improve Droskidrink® (DD), a commercially available attractant for SWD. We focused on the chemical and behavioral effects of adding the bacterium Oenococcus oeni (Garvie) to DD and used a new trap design to enhance the effects of attractive lures. We demonstrate that microbial volatile compounds produced by O. oeni are responsible for the increase in the attractiveness of the bait and could be later utilized for the development of a better trapping system. Our results showed that the attractiveness of DD was increased up to two-fold by the addition of commercially available O. oeni when combined with an innovative trap design. The new trap-bait combination increased the number of male and especially female catches at low population densitie