Ectopic hbox12 Expression Evoked by Histone Deacetylase Inhibition Disrupts Axial Specification of the Sea Urchin Embryo

Dorsal/ventral patterning of the sea urchin embryo depends upon the establishment of a Nodal-expressing ventral organizer. Recently, we showed that spatial positioning of this organizer relies on the dorsal-specific transcription of the Hbox12 repressor. Building on these findings, we determined the influence of the epigenetic milieu on the expression of hbox12 and nodal genes. We find that Trichostatin-A, a potent and selective histone-deacetylases inhibitor, induces histone hyperacetylation in hbox12 chromatin, evoking broad ectopic expression of the gene. Transcription of nodal concomitantly drops, prejudicing dorsal/ventral polarity of the resulting larvae. Remarkably, impairing hbox12 function, either in a spatially-restricted sector or in the whole embryo, specifically rescues nodal transcription in Trichostatin-A-treated larvae. Beyond strengthen the notion that nodal expression is not allowed in the presence of functional Hbox12 in the same cells, these results highlight a critical role of histone deacetylases in regulating the spatial expression of hbox12

Possible observation of parametrically amplified coherent phasons in K0.3MoO3 using time-resolved extreme-ultraviolet ARPES

We use time- and angle-resolved photoemission spectroscopy (tr-ARPES) in the Extreme Ultraviolet (EUV) to measure the time- and momentum-dependent electronic structure of photo-excited K0.3MoO3. Prompt depletion of the Charge Density Wave (CDW) condensate launches coherent oscillations of the amplitude mode, observed as a 1.7-THz-frequency modulation of the bonding band position. In contrast, the anti-bonding band oscillates at about half this frequency. We attribute these oscillations to coherent excitation of phasons via parametric amplification of phase fluctuations.Comment: 4 figure

Supersonic strain front driven by a dense electron-hole plasma

We study coherent strain in (001) Ge generated by an ultrafast laser-initiated high density electron-hole plasma. The resultant coherent pulse is probed by time-resolved x-ray diffraction through changes in the anomalous transmission. The acoustic pulse front is driven by ambipolar diffusion of the electron-hole plasma and propagates into the crystal at supersonic speeds. Simulations of the strain including electron-phonon coupling, modified by carrier diffusion and Auger recombination, are in good agreement with the observed dynamics.Comment: 4 pages, 6 figure

Multi-membership gene regulation in pathway based microarray analysis

This article is available through the Brunel Open Access Publishing Fund. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Gene expression analysis has been intensively researched for more than a decade. Recently, there has been elevated interest in the integration of microarray data analysis with other types of biological knowledge in a holistic analytical approach. We propose a methodology that can be facilitated for pathway based microarray data analysis, based on the observation that a substantial proportion of genes present in biochemical pathway databases are members of a number of distinct pathways. Our methodology aims towards establishing the state of individual pathways, by identifying those truly affected by the experimental conditions based on the behaviour of such genes. For that purpose it considers all the pathways in which a gene participates and the general census of gene expression per pathway. Results: We utilise hill climbing, simulated annealing and a genetic algorithm to analyse the consistency of the produced results, through the application of fuzzy adjusted rand indexes and hamming distance. All algorithms produce highly consistent genes to pathways allocations, revealing the contribution of genes to pathway functionality, in agreement with current pathway state visualisation techniques, with the simulated annealing search proving slightly superior in terms of efficiency. Conclusions: We show that the expression values of genes, which are members of a number of biochemical pathways or modules, are the net effect of the contribution of each gene to these biochemical processes. We show that by manipulating the pathway and module contribution of such genes to follow underlying trends we can interpret microarray results centred on the behaviour of these genes.The work was sponsored by the studentship scheme of the School of Information Systems, Computing and Mathematics, Brunel Universit

Inertial control of the mirror suspensions of the VIRGO interferometer for gravitational wave detection

In order to achieve full detection sensitivity at low frequencies, the mirrors of interferometric gravitational wave detectors must be isolated from seismic noise. The VIRGO vibration isolator, called 'superattenuator', is fully effective at frequencies above 4 Hz. Nevertheless, the residual motion of the mirror at the mechanical resonant frequencies of the system are too large for the interferometer locking system and must be damped. A multidimensional feedback system, using inertial sensors and digital processing, has been designed for this purpose. An experimental procedure for determining the feedback control of the system has been defined. In this paper a full description of the system is given and experimental results are presented.Comment: 17 pages, 11 figures, accepted for publication on Review of Scientific Instrument

Develop a cost model to evaluate the economic benefit of remanufacturing based on specific technique

Remanufacturing is a process of recovering used products to a like-new condition. It can potentially achieve considerable economic, environmental and social benefits in many applications. However, its economic benefit varies for different products and remanufacturing processes. This research aims to develop a framework and cost model to quantitatively evaluate the benefits of remanufacturing techniques to assist the decision making on end-of-life strategies. Additive manufacturing-based remanufacturing process has been modelled first, then cost breakdown structure for the process has been created, and the cost model has been developed. Validation of the cost model has been conducted based on expert judgement, and a case study has been carried out by using the developed cost model to compare the benefit of remanufacturing a specified component or making a new one

How Much Do Focal Infarcts Distort White Matter Lesions and Global Cerebral Atrophy Measures?

BACKGROUND: White matter lesions (WML) and brain atrophy are important biomarkers in stroke and dementia. Stroke lesions, either acute or old, symptomatic or silent, are common in older people. Such stroke lesions can have similar signals to WML and cerebrospinal fluid (CSF) on magnetic resonance (MR) images, and may be classified accidentally as WML or CSF by MR image processing algorithms, distorting WML and brain atrophy volume from the true volume. We evaluated the effect that acute or old stroke lesions at baseline, and new stroke lesions occurring during follow-up, could have on measurement of WML volume, cerebral atrophy and their longitudinal progression. METHODS: We used MR imaging data from patients who had originally presented with acute lacunar or minor cortical ischaemic stroke symptoms, recruited prospectively, who were scanned at baseline and about 3 years later. We measured WML and CSF volumes (ml) semi-automatically. We manually outlined the acute index stroke lesion (ISL), any old stroke lesions present at baseline, and new lesions appearing de novo during follow-up. We compared baseline and follow-up WML volume, cerebral atrophy and their longitudinal progression excluding and including the acute ISL, old and de novo stroke lesions. A non-parametric test (Wilcoxon's signed rank test) was used to compare the effects. RESULTS: Among 46 patients (mean age 72 years), 33 had an ISL visible on MR imaging (median volume 2.05 ml, IQR 0.88–8.88) and 7 of the 33 had old lacunes at baseline: WML volume was 8.54 ml (IQR 5.86–15.80) excluding versus 10.98 ml (IQR 6.91–24.86) including ISL (p < 0.001). At follow-up, median 39 months later (IQR 30–45), 3 patients had a de novo stroke lesion; total stroke lesion volume had decreased in 11 and increased in 22 patients: WML volume was 12.17 ml (IQR 8.54–19.86) excluding versus 14.79 ml (IQR 10.02–38.03) including total stroke lesions (p < 0.001). Including/excluding lacunes at baseline or follow-up also made small differences. Twenty-two of the 33 patients had tissue loss due to stroke lesions between baseline and follow-up, resulting in a net median brain tissue volume loss (i.e. atrophy) during follow-up of 24.49 ml (IQR 12.87–54.01) excluding versus 24.61 ml (IQR 15.54–54.04) including tissue loss due to stroke lesions (p < 0.001). Including stroke lesions in the WML volume added substantial noise, reduced statistical power, and thus increased sample size estimated for a clinical trial. CONCLUSIONS: Failure to exclude even small stroke lesions distorts WML volume, cerebral atrophy and their longitudinal progression measurements. This has important implications for design and sample size calculations for observational studies and randomised trials using WML volume, WML progression or brain atrophy as outcome measures. Improved methods of discriminating between stroke lesions and WML, and between tissue loss due to stroke lesions and true brain atrophy are required

Towards a Decision Support Tool for Assessing, Managing and Mitigating Seismic Risk of Electric Power Networks

Recent seismic event worldwide proved how fragile the electric power system can be to seismic events. Decision Support Systems (DSSs) could have a critical role in assessing the seismic risk of electric power networks and in enabling asset managers to test the effectiveness of alternative mitigation strategies and investments on resilience. This paper exemplifies the potentialities of CIPCast, a DSS recently created in the framework of the EU-funded project CIPRNet, to perform such tasks. CIPCast enables to perform risk assessment for Critical Infrastructures (CI) when subjected to different natural hazards, including earthquakes. An ad-hoc customization of CIPCast for the seismic risk analysis and management of electric power networks is featured in this paper. The international literature describes effective and sound efforts towards the creation of software platforms and frameworks for the assessment of seismic risk of electric power networks. None of them, unfortunately, achieved the goal of creating a user-friendly and ready available DDS to be used by asset managers, local authorities and civil protection departments. Towards that and building on the international literature, the paper describes metrics and methods to be integrated within CIPCast for assessing the earthquake-induced physical and functional impacts of the electric power network at component and system level. The paper describes also how CIPCast can inform the service restoration process

Partial Inhibition of Estrogen-Induced Mammary Carcinogenesis in Rats by Tamoxifen: Balance between Oxidant Stress and Estrogen Responsiveness

Epidemiological and experimental evidences strongly support the role of estrogens in breast tumor development. Both estrogen receptor (ER)-dependent and ER-independent mechanisms are implicated in estrogen-induced breast carcinogenesis. Tamoxifen, a selective estrogen receptor modulator is widely used as chemoprotectant in human breast cancer. It binds to ERs and interferes with normal binding of estrogen to ERs. In the present study, we examined the effect of long-term tamoxifen treatment in the prevention of estrogen-induced breast cancer. Female ACI rats were treated with 17β-estradiol (E2), tamoxifen or with a combination of E2 and tamoxifen for eight months. Tissue levels of oxidative stress markers 8-iso-Prostane F2α (8-isoPGF2α), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, and oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG) were quantified in the mammary tissues of all the treatment groups and compared with age-matched controls. Levels of tamoxifen metabolizing enzymes cytochrome P450s as well as estrogen responsive genes were also quantified. At necropsy, breast tumors were detected in 44% of rats co-treated with tamoxifen+E2. No tumors were detected in the sham or tamoxifen only treatment groups whereas in the E2 only treatment group, the tumor incidence was 82%. Co-treatment with tamoxifen decreased GPx and catalase levels; did not completely inhibit E2-mediated oxidative DNA damage and estrogen-responsive genes monoamine oxygenase B1 (MaoB1) and cell death inducing DFF45 like effector C (Cidec) but differentially affected the levels of tamoxifen metabolizing enzymes. In summary, our studies suggest that although tamoxifen treatment inhibits estrogen-induced breast tumor development and increases the latency of tumor development, it does not completely abrogate breast tumor development in a rat model of estrogen-induced breast cancer. The inability of tamoxifen to completely inhibit E2-induced breast carcinogenesis may be because of increased estrogen-mediated oxidant burden