Phase I and II biotransformation enzymes and polycyclic aromatic hydrocarbons in the Mediterranean mussel (Mytilus galloprovincialis, Lamarck, 1819) collected in front of an oil refinery

The aim of the present study was to investigate the responses of phase I and II biotransformation enzymes and levels of PAHs in the Mediterranean mussel (Mytilus galloprovincialis, Lamarck, 1819) collected from three sites at different distance from an oil refinery. Phase I enzyme activities as NAD(P)H-cyt c red, NADH ferry red, B(a)PMO and phase II as UDPGT. GST were measured in digestive gland while 16 PAHs (US-EPA) in whole soft tissue. An added value to the data obtained in the present study rely on the RDA analysis which showed close correlations between PAHs levels and phase I enzyme activities in mussels collected in front of the refinery. And again a significant spatial correlation between B(a)P levels and NADPH-cyt c red activities was observed using linear models. No differences among sites for B(a) PMO and phase II GST activities were observed, while the application of UDPGT as biomarkers requires further investigation. (C) 2012 Elsevier Ltd. All rights reserved.

Next generation sequencing-based molecular diagnosis of retinitis pigmentosa: identification of a novel genotype-phenotype correlation and clinical refinements

Retinitis pigmentosa (RP) is a devastating form of retinal degeneration, with significant social and professional consequences. Molecular genetic information is invaluable for an accurate clinical diagnosis of RP due to its high genetic and clinical heterogeneity. Using a gene capture panel that covers 163 of the currently known retinal disease genes, including 48 RP genes, we performed a comprehensive molecular screening in a collection of 123 RP unsettled probands from a wide variety of ethnic backgrounds, including 113 unrelated simplex and 10 autosomal recessive RP (arRP) cases. As a result, 61 mutations were identified in 45 probands, including 38 novel pathogenic alleles. Interestingly, we observed that phenotype and genotype were not in full agreement in 21 probands. Among them, eight probands were clinically reassessed, resulting in refinement of clinical diagnoses for six of these patients. Finally, recessive mutations in CLN3 were identified in five retinal degeneration patients, including four RP probands and one cone-rod dystrophy patient, suggesting that CLN3 is a novel non-syndromic retinal disease gene. Collectively, our results underscore that, due to the high molecular and clinical heterogeneity of RP, comprehensive screening of all retinal disease genes is effective in identifying novel pathogenic mutations and provides an opportunity to discover new genotype-phenotype correlations. Information gained from this genetic screening will directly aid in patient diagnosis, prognosis, and treatment, as well as allowing appropriate family planning and counseling.

Revised response criteria for polycythemia vera and essential thrombocythemia:an ELN and IWG-MRT consensus project

Standardized response criteria to interpret and compare clinical trials are needed for approval of new therapeutic agents by regulatory agencies. The European LeukemiaNet (ELN) response criteria for essential thrombocythemia (ET) and polycythemia vera (PV) issued in 2009 have been widely adopted as end points in a number of recent clinical trials. However, evidence exists that they do not predict response or provide clinically relevant measures of benefit for the patients. This article presents revised recommendations for assessing response in ET and PV provided by a working group established by ELN and International Working Group-Myeloproliferative Neoplasms Research and Treatment. New definitions of complete and partial remission incorporate clinical, hematological, and histological response assessments that include a standardized symptom assessment form and consider absence of disease progression and vascular events. We anticipate that these criteria will be adopted widely to facilitate the development of new and more effective therapies for ET and PV.

Reconfigurable Long-Range Phonon Dynamics in Optomechanical Arrays

We investigate periodic optomechanical arrays as reconfigurable platforms for engineering the coupling between multiple mechanical and electromagnetic modes and for exploring many-body phonon dynamics. Exploiting structural resonances in the coupling between light fields and collective motional modes of the array, we show that tunable effective long-range interactions between mechanical modes can be achieved. This paves the way towards the implementation of controlled phononic walks and heat transfer on densely connected graphs as well as the coherent transfer of excitations between distant elements of optomechanical arrays.

Monodomain strained ferroelectric PbTiO(3) thin films: Phase transition and critical thickness study

This work demonstrates that instead of paraelectric PbTiO(3), completely c-oriented ferroelectric PbTiO(3) thin films were directly grown on (001)-SrTiO(3) substrates by pulsed-laser deposition with thickness up to 340 nm at a temperature well above the Curie temperature of bulk PbTiO(3). The influence of laser-pulse frequency, substrate-surface termination on growth, and functional properties were studied using x-ray diffraction, transmission electron microscopy, and piezoresponse force microscopy. At low growth rates (frequency 8 Hz) a domains were formed for film thickness above 20-100 nm. Due to coherency strains the Curie temperature (T(c)) of the monodomain films was increased approximately by 350 degrees C with respect to the T(c) of bulk PbTiO(3) even for 280-nm-thick films. Nonetheless, up to now this type of growth mode has been considered unlikely to occur since the Matthews-Blakeslee (MB) model already predicts strain relaxation for films having a thickness of only similar to 10 nm. However, the present work disputes the applicability of the MB model. It clarifies the physical reasons for the large increase in T(c) for thick films, and it is shown that the experimental results are in good agreement with the predictions based on the monodomain model of Pertsev et al. [Phys. Rev. Lett. 80, 1988 (1998)].

Low dose effects of ionizing radiation on normal tissue stem cells

In recent years, there has been growing evidence for the involvement of stem cells in cancer initiation. As a result of their long life span, stem cells may have an increased propensity to accumulate genetic damage relative to differentiated cells. Therefore, stem cells of normal tissues may be important targets for radiation-induced carcinogenesis.

Knowledge of the effects of ionizing radiation (IR) on normal stem cells and on the processes involved in carcinogenesis is very limited. The influence of high doses of IR (>5 Gy) on proliferation, cell cycle and induction of senescence has been demonstrated in stem cells. There have been limited studies of the effects of moderate (0.5–5 Gy) and low doses (<0.5 Gy) of IR on stem cells however, the effect of low dose IR (LD-IR) on normal stem cells as possible targets for radiation-induced carcinogenesis has not been studied in any depth. There may also be important parallels between stem cell responses and those of cancer stem cells, which may highlight potential key common mechanisms of their response and radiosensitivity.

This review will provide an overview of the current knowledge of radiation-induced effects on normal stem cells, with particular focus on low and moderate doses of IR.

Non-targeted effects of ionising radiation-Implications for low dose risk

Non-DNA targeted effects of ionising radiation, which include genomic instability, and a variety of bystander effects including abscopal effects and bystander mediated adaptive response, have raised concerns about the magnitude of low-dose radiation risk. Genomic instability, bystander effects and adaptive responses are powered by fundamental, but not clearly understood systems that maintain tissue homeostasis. Despite excellent research in this field by various groups, there are still gaps in our understandfng of the likely mechanisms associated with non-DNA targeted effects, particularly with respect to systemic (human health) consequences at low and intermediate doses of ionising radiation. Other outstanding questions include links between the different non-targeted responses and the variations. in response observed between individuals and cell lines, possibly a function of genetic background. Furthermore, it is still not known what the initial target and early interactions in cells are that give rise to non-targeted responses in neighbouring or descendant cells. This paper provides a commentary on the current state of the field as a result of the non-targeted effects of ionising radiation (NOTE) Integrated Project funded by the European Union. Here we critically examine the evidence for non-targeted effects, discuss apparently contradictory results and consider implications for low-dose radiation health effects. (C) 2012 Elsevier B.V. All rights reserved.

Enhanced optomechanical readout using optical coalescence

We present a scheme to strongly enhance the readout sensitivity of the squared displacement of a mobile scatterer placed in a Fabry-Pérot cavity. We investigate the largely unexplored regime of cavity electrodynamics in which a highly reflective element positioned between the end mirrors of a symmetric Fabry-Pérot resonator strongly modifies the cavity response function, such that two longitudinal modes with different spatial parity are brought close to frequency degeneracy and interfere in the cavity output field. In the case of a movable middle reflector we show that the interference in this generic "optical coalescence" phenomenon gives rise to an enhanced frequency shift of the peaks of the cavity transmission that can be exploited in optomechanics. © 2013 American Physical Society.

Incorporating PGMs into a BDI Architecture

In this paper, we present a hybrid BDI-PGM framework, in which PGMs (Probabilistic Graphical Models) are incorporated into a BDI (belief-desire-intention) architecture. This work is motivated by the need to address the scalability and noisy sensing issues in SCADA (Supervisory Control And Data Acquisition) systems. Our approach uses the incorporated PGMs to model the uncertainty reasoning and decision making processes of agents situated in a stochastic environment. In particular, we use Bayesian networks to reason about an agent’s beliefs about the environment based on its sensory observations, and select optimal plans according to the utilities of actions defined in influence diagrams. This approach takes the advantage of the scalability of the BDI architecture and the uncertainty reasoning capability of PGMs. We present a prototype of the proposed approach using a transit scenario to validate its effectiveness.

Molecular diagnostics of myeloproliferative neoplasms

Since the discovery of the JAK2 V617F mutation in the majority of the myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia and primary myelofibrosis ten years ago, further MPN-specific mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been identified. These discoveries have been rapidly incorporated into evolving molecular diagnostic algorithms. While many of these mutations appear to have prognostic implications, establishing MPN diagnosis is of immediate clinical importance with selection, implementation and the continual evaluation of the appropriate laboratory methodology to achieve this diagnosis similarly vital. The advantages and limitations of these approaches in identifying and quantitating the common MPN-associated mutations is considered herein with particular regard to their clinical utility. The evolution of molecular diagnostic applications and platforms has occurred in parallel with the discovery of MPN-associated mutations and it therefore appears likely that emerging technologies such as next-generation sequencing and digital PCR will in the future, play an increasing role in the molecular diagnosis of MPN. 

Characterisation of melt processed nanocomposites of Polyamide 6 subjected to uniaxial-drawing

In this paper, the processing and characterization of Polyamide 6 (PA6) nanocomposites containing graphite nanoplatelets (GNPs) is reported. PA6 nanocomposites were prepared by melt-mixing using an industrial, co-rotating, intermeshing, twin-screw extruder. A bespoke screw configuration was used that was designed in-house to enhance nanoparticle dispersion into a polymer matrix. The effects of nano-filler type (xGnPTM M-5 and xGnPTM C-500), nano-filler content, and extruder screw speed on the bulk properties of the PA6 nanocomposites were investigated. The crystalline structures of PA6 nanocomposites are related to thermal treatment, stress history and the presence of moisture and nanofillers. DSC, Raman and XRD studies show an increase in crystallinity with increasing GNP content and a phase transformation between α-form to γ-form crystals as a result of the heterophase nucleation effect. The effect of uniaxial stretching on PA6 nanocomposites was investigated by drawing specimens heated at temperatures below the melting temperature. DSC and Raman studies on the drawn samples show an increase in yield stress as the GNP content increases due to the strain induced crystallization and γ—β transition during stretching. The rheological response of the nanocomposites resemble that of a ‘pseudo-solid’, rather than a molten liquid, and analysis of the rheological data indicates that a percolation threshold was reached at GNP contents of between 10–15wt%. An increase in tensile modulus of as much as 412% was observed for PA6/C-500 xGnPTM composites, at a filler content of 20wt%. The enhancement of Young’s modulus and yield stress can be attributed to the reinforcing effect of GNPs and their uniform dispersion in the PA6 matrix. The electrical conductivity of the composite also increased with increasing GNP content, with an addition of 15wt% GNP resulting in a 6 order-of-magnitude increase in conductivity. The effects of uniaxial-drawing and the inclusion of multiple nano-filler varieties on the electrical and mechanical properties are currently under investigation.