The BH3-only protein Bik/Blk/Nbk inhibits nuclear translocation of activated ERK1/2 to mediate IFNγ-induced cell death

IFNγ induces cell death in epithelial cells, but the mediator for this death pathway has not been identified. In this study, we find that expression of Bik/Blk/Nbk is increased in human airway epithelial cells (AECs [HAECs]) in response to IFNγ. Expression of Bik but not mutant BikL61G induces and loss of Bik suppresses IFNγ-induced cell death in HAECs. IFNγ treatment and Bik expression increase cathepsin B and D messenger RNA levels and reduce levels of phospho–extracellular regulated kinase 1/2 (ERK1/2) in the nuclei of bik+/+ compared with bik−/− murine AECs. Bik but not BikL61G interacts with and suppresses nuclear translocation of phospho-ERK1/2, and suppression of ERK1/2 activation inhibits IFNγ- and Bik-induced cell death. Furthermore, after prolonged exposure to allergen, hyperplastic epithelial cells persist longer, and nuclear phospho-ERK is more prevalent in airways of IFNγ−/− or bik−/− compared with wild-type mice. These results demonstrate that IFNγ requires Bik to suppress nuclear localization of phospho-ERK1/2 to channel cell death in AECs

Kinetics and Isotherms of a Genetically Engineered Saccharomyces Cerevisiae EBY100 Strain Expressing Palladium Binding Peptides for the Biosorption of Pd (II) in a Batch Reactor

Palladium is a rare platinum group metal concentrated in the Earth's core and mantle; because of its scarcity, its waste recovery and reuse options are economically appealing.Traditional strategies for extracting PGMs from effluents have a variety of flaws, prompting researchers to search for novel methods. One such method is biosorption.A novel biosorbent in the form of a genetically engineered strain of Saccharomyces cerevisiae EBY100 has been developed for the biosorption of palladium in aqueous solution.The genetically modified Saccharomyces cerevisiae EBY100 strain was created to display palladium-binding peptides on its surface. The purpose of this study was to characterize the adsorption of Pd(II) by a genetically modified strain of Saccharomyces cerevisiae EBY100 in a batch reactor using isotherm and kinetic studies.The maximum adsorption capacity of transformed S.cerevisiae EBY100 cells for Pd(II) ions was found to be 125 mg/g; adsorption was found to be best described by the Freundlich isotherm and pseudo-second order models

Model-based tool support for Tactical Data Links: an experience report from the defence domain

The Tactical Data Link (TDL) allows the exchange of information between cooperating platforms as part of an integrated command and control (C2) system. Information exchange is facilitated by adherence to a complex, message-based protocol defined by document-centric standards. In this paper, we report on a recent body of work investigating migration from a document-centric to a model-centric approach within the context of the TDL domain, motivated by a desire to achieve a positive return on investment. The model-centric approach makes use of the Epsilon technology stack and provides a significant improvement to both the level of abstraction and rigour of the network design. It is checkable by a machine and, by virtue of an MDA-like approach to the separation of domains and model transformation between domains, is open to integration with other models to support more complex workflows, such as by providing the results of interoperability analyses in human-readable domain-specific reports conforming to an accepted standard

Contrasting vulnerability of drained tropical and high-latitude peatlands to fluvial loss of stored carbon

Carbon sequestration and storage in peatlands rely on consistently highwater tables. Anthropogenic pressures including drainage, burning, land conversion for agriculture, timber, and biofuel production, cause loss of peat-forming vegetation and exposure of previously anaerobic peat to aerobic decomposition. This can shift peatlands from net CO2 sinks to large CO2 sources, releasing carbon held for millennia. Peatlands also export significant quantities of carbon via fluvial pathways, mainly as dissolved organic carbon (DOC). We analyzed radiocarbon (14C) levels of DOC in drainage water from multiple peatlands in Europe and Southeast Asia, to infer differences in the age of carbon lost from intact and drained systems. In most cases, drainage led to increased release of older carbon from the peat profile but withmarked differences related to peat type. Very low DOC-14C levels in runoff from drained tropical peatlands indicate loss of very old (centuries to millennia) stored peat carbon. High-latitude peatlands appear more resilient to drainage; 14C measurements from UK blanket bogs suggest that exported DOC remains young (500 year) carbon in high-latitude systems. Rewetting at least partially offsets drainage effects on DOC age

On Poincare and logarithmic Sobolev inequalities for a class of singular Gibbs measures

This note, mostly expository, is devoted to Poincar{\'e} and log-Sobolev inequalities for a class of Boltzmann-Gibbs measures with singular interaction. Such measures allow to model one-dimensional particles with confinement and singular pair interaction. The functional inequalities come from convexity. We prove and characterize optimality in the case of quadratic confinement via a factorization of the measure. This optimality phenomenon holds for all beta Hermite ensembles including the Gaussian unitary ensemble, a famous exactly solvable model of random matrix theory. We further explore exact solvability by reviewing the relation to Dyson-Ornstein-Uhlenbeck diffusion dynamics admitting the Hermite-Lassalle orthogonal polynomials as a complete set of eigenfunctions. We also discuss the consequence of the log-Sobolev inequality in terms of concentration of measure for Lipschitz functions such as maxima and linear statistics.Comment: Minor improvements. To appear in Geometric Aspects of Functional Analysis -- Israel Seminar (GAFA) 2017-2019", Lecture Notes in Mathematics 225

Bottomonium in the plasma: Lattice results

We present results on the heavy quarkonium spectrum and spectral functions obtained by performing large-scale simulations of QCD for temperatures ranging from about 100 to 500 MeV, in the same range as those explored by LHC experiments. We discuss our method and perspectives for further improvements towards the goal of full control over the many systematic uncertainties of these studies

The Angelina Jolie effect : how high celebrity profile can have a major impact on provision of cancer related services

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements We acknowledge the support of the Genesis Breast Cancer Prevention Appeal and Breast Cancer Campaign, which funds the FH02 study. DGE is a NIHR Senior investigator. FH02 Study Group, Family History Clinics providing data is as follows, Edinburgh: Lynda Luke, Lesley Smart; St Barts, London: Vian Salih, Ilyena Froud; Grantham: Nicky Turner, Natarajan Vaithilingam; Leighton Hospital Crewe: Tracey Hales, Samantha Bennion; LondonDerry: Celia Diver-Hall, Jackie McGee; Nottingham: Douglas MacMillan; Nicky Scott; Bath: Diana Dalgleish, Alison Smith; Coventry: Celia Lewis; Royal Marsden Hospital, London: Janet self, Gerald Gui; Derby: Mark Sibbering, Samantha Crockett; City Hospital, Birmingham: Simerjit Rai, Harriet Goddard; Genesis Prevention Centre, Manchester: Lorraine Roberts, Jayne Beesley. RGC teams are as follows, Nottingham RGC: Gareth Cross; Guys Hospital: Adam Shaw; Manchester RGC: Andrew Wallace.Peer reviewedPublisher PD

The Extratropical Transition of Tropical Cyclones: Forecast Challenges, Current Understanding, and Future Directions

A significant number of tropical cyclones move into the midlatitudes and transform into extratropical cyclones. This process is generally referred to as extratropical transition (ET). During ET a cyclone frequently produces intense rainfall and strong winds and has increased forward motion, so that such systems pose a serious threat to land and maritime activities. Changes in the structure of a system as it evolves from a tropical to an extratropical cyclone during ET necessitate changes in forecast strategies. In this paper a brief climatology of ET is given and the challenges associated with forecasting extratropical transition are described in terms of the forecast variables (track, intensity, surface winds, precipitation) and their impacts (flooding, bush fires, ocean response). The problems associated with the numerical prediction of ET are discussed. A comprehensive review of the current understanding of the processes involved in ET is presented. Classifications of extratropical transition are described and potential vorticity thinking is presented as an aid to understanding ET. Further sections discuss the interaction between a tropical cyclone and the midlatitude environment, the role of latent heat release, convection and the underlying surface in ET, the structural changes due to frontogenesis, the mechanisms responsible for precipitation, and the energy budget during ET. Finally, a summary of the future directions for research into ET is given

Lifestyle and Genetic Factors Modify Parent-of-Origin Effects on the Human Methylome

BACKGROUND: parent-of-origin effects (POE) play important roles in complex disease and thus understanding their regulation and associated molecular and phenotypic variation are warranted. Previous studies mainly focused on the detection of genomic regions or phenotypes regulated by POE. Understanding whether POE may be modified by environmental or genetic exposures is important for understanding of the source of POE-associated variation, but only a few case studies addressing modifiable POE exist. METHODS: in order to understand this high order of POE regulation, we screened 101 genetic and environmental factors such as ‘predicted mRNA expression levels’ of DNA methylation/imprinting machinery genes and environmental exposures. POE-mQTL-modifier interaction models were proposed to test the potential of these factors to modify POE at DNA methylation using data from Generation Scotland: The Scottish Family Health Study(N=2315). FINDINGS: a set of vulnerable/modifiable POE-CpGs were identified (modifiable-POE-regulated CpGs, N=3). Four factors, ‘lifetime smoking status’ and ‘predicted mRNA expression levels’ of TET2, SIRT1 and KDM1A, were found to significantly modify the POE on the three CpGs in both discovery and replication datasets. We further identified plasma protein and health-related phenotypes associated with the methylation level of one of the identified CpGs. INTERPRETATION: the modifiable POE identified here revealed an important yet indirect path through which genetic background and environmental exposures introduce their effect on DNA methylation, motivating future comprehensive evaluation of the role of these modifiers in complex diseases. FUNDING: NSFC (81971270),H2020-MSCA-ITN(721815), Wellcome (204979/Z/16/Z,104036/Z/14/Z), MRC (MC_UU_00007/10, MC_PC_U127592696), CSO (CZD/16/6,CZB/4/276, CZB/4/710), SFC (HR03006), EUROSPAN (LSHG-CT-2006-018947), BBSRC (BBS/E/D/30002276), SYSU, Arthritis Research UK, NHLBI, NIH

Conceptualising sustainability in UK urban Regeneration: a discursive Formation

Despite the wide usage and popular appeal of the concept of sustainability in UK policy, it does not appear to have challenged the status quo in urban regeneration because policy is not leading in its conceptualisation and therefore implementation. This paper investigates how sustainability has been conceptualised in a case-based research study of the regeneration of Eastside in Birmingham, UK, through policy and other documents, and finds that conceptualisations of sustainability are fundamentally limited. The conceptualisation of sustainability operating within urban regeneration schemes should powerfully shape how they make manifest (or do not) the principles of sustainable development. Documents guide, but people implement regeneration—and the disparate conceptualisations of stakeholders demonstrate even less coherence than policy. The actions towards achieving sustainability have become a policy ‘fix’ in Eastside: a necessary feature of urban policy discourse that is limited to solutions within market-based constraints