Role of p21 activated kinase in zebrafish lateral line development.

Migration of the posterior lateral line primordium is a process of directed response to a chemotactic signal. We have observed directional protrusions of the cells at the leading edge of migrating primordia. The p21 activated kinase (Pak) family of proteins are downstream effectors of the small GTPases Rac and Cdc42 and have been shown to play important roles in the regulation of cell adhesion and migration in many organisms. In order to understand the molecular mechanisms underlying directed cell migration in zebrafish we have identified and characterised two zebrafish pak2 genes {lcub}pak2a and pak2b) and found that their functions are important for migration of the lateral line primordium. Pak2a and Pak2b have similar protein sequences suggesting similar functions in development. Knock down of Pak2 using antisense morpholino oligonucleotides resulted in a variety of defects in zebrafish development including retarded migration of the posterior lateral line primordium and aberrant migration of primordial germ cells. Zebrafish pak2 genes may function by dynamically regulating the F-actin reorganisation and focal adhesion formation required for directed migration. Differences in the phenotypes generated by knock down of Pak2a and Pak2b may be explained in part by the observation that Pak2a can bind to the adaptor protein Nek while Pak2b cannot. Pak2b is required to establish and/or maintain F-actin organisation, cadherin- mediated adhesion and tissue integrity within the migrating lateral line primordium. We show that dynamic regulation of the actin cytoskeleton and cell adhesion is involved in the formation of rosette-like structures within the lateral line primordium which are deposited as a unit and represent the nascent neuromast precursors. We have also identified possible roles for Pak2a and Pak2b in regulating gene expression in early zebrafish development. Pak2 proteins may control the expression of several genes involved in mesoderm formation through regulation of transcriptional activators and repressors

New constructions of twistor lifts for harmonic maps

We show that given a harmonic map $\varphi$ from a Riemann surface to a classical compact simply connected inner symmetric space, there is a $J_2$-holomorphic twistor lift of $\varphi$ (or its negative) if and only if it is nilconformal. In the case of harmonic maps of finite uniton number, we give algebraic formulae in terms of holomorphic data which describes their extended solutions. In particular, this gives explicit formulae for the twistor lifts of all harmonic maps of finite uniton number from a surface to the above symmetric spaces.Comment: Some minor changes and a correction of Example 8.

Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia

A comprehensive international consensus on the cytogenetic risk-group stratification of KMT2A-rearranged (KMT2A-r) pediatric acute myeloid leukemia (AML) is lacking. This retrospective (2005-2016) International Berlin-Frankfurt-Münster Study Group study on 1256 children with KMT2A-r AML aims to validate the prognostic value of established recurring KMT2A fusions and additional cytogenetic aberrations (ACAs) and to define additional, recurring KMT2A fusions and ACAs, evaluating their prognostic relevance. Compared with our previous study, 3 additional, recurring KMT2A-r groups were defined: Xq24/KMT2A::SEPT6, 1p32/KMT2A::EPS15, and 17q12/t(11;17)(q23;q12). Across 13 KMT2A-r groups, 5-year event-free survival probabilities varied significantly (21.8%-76.2%; P &lt; .01). ACAs occurred in 46.8% of 1200 patients with complete karyotypes, correlating with inferior overall survival (56.8% vs 67.9%; P &lt; .01). Multivariable analyses confirmed independent associations of 4q21/KMT2A::AFF1, 6q27/KMT2A::AFDN, 10p12/KMT2A::MLLT10, 10p11.2/KMT2A::ABI1, and 19p13.3/KMT2A::MLLT1 with adverse outcomes, but not those of 1q21/KMT2A::MLLT11 and trisomy 19 with favorable and adverse outcomes, respectively. Newly identified ACAs with independent adverse prognoses were monosomy 10, trisomies 1, 6, 16, and X, add(12p), and del(9q). Among patients with 9p22/KMT2A::MLLT3, the independent association of French-American-British-type M5 with favorable outcomes was confirmed, and those of trisomy 6 and measurable residual disease at end of induction with adverse outcomes were identified. We provide evidence to incorporate 5 adverse-risk KMT2A fusions into the cytogenetic risk-group stratification of KMT2A-r pediatric AML, to revise the favorable-risk classification of 1q21/KMT2A::MLLT11 to intermediate risk, and to refine the risk-stratification of 9p22/KMT2A::MLLT3 AML. Future studies should validate the associations between the newly identified ACAs and outcomes and unravel the underlying biological pathogenesis of KMT2A fusions and ACAs.</p

Health providers as bricoleurs:an examination of the adaption of health ecosystems to superdiversity in Europe

This article examines the ways in which healthcare providers from a mixed economy of welfare operating in superdiverse neighbourhoods connect and innovate across the healthcare ecosystem to meet diverse and complex needs. Moving beyond a health systems approach which siloes different types of provision, we use the concept of bricolage to make visible the work undertaken by providers across the ecosystem. While we show that public, private and civil society provision all adapt to meet complex and diverse needs to some degree, we highlight the importance of inter-connectedness between providers and note the role of civil society in addressing gaps and cracks in provision. The importance of adopting a whole ecosystem approach and focusing on the actions and interactions which enable the ecosystem to function in complex demographic environments is highlighted before we stress the dangers of over-reliance on civil society.info:eu-repo/semantics/acceptedVersio

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Legal, medical and lay understanding of embryos in Portugal: alignment with biology?

Pretende-se contribuir para o debate em torno dos processos de circulação de conhecimentos e sentidos entre especialistas e “leigos” no que concerne ao estatuto dos embriões humanos em Portugal. Reflete-se sobre as expectativas e preocupações manifestadas quanto à confiança, qualidade, segurança e eficácia das tecnologias médicas de reprodução assistida. O estudo assenta na realização de entrevistas individuais, com vistas a explorar as complexidades, similitudes e diferenças entre as visões e os valores de juristas, médicos e casais envolvidos em tratamentos de fertilização in vitro. Trata-se de uma análise qualitativa em um estudo de caso. Se os juristas e os médicos enquadram o estatuto dos embriões em categorias de índole biológica, técnica e/ou jurídico-legal, já os casais estabelecem com os mesmos diversas relações ontológicas de índole moral, afetiva e social, pelo que estes podem ser representados como seres éticos face à biologização médico-legal dos embriões.Our aim is to contribute towards the debate about the processes through which knowledge and meanings regarding the status of human embryos circulate among experts and laymen in Portugal. Expectations and concerns expressed regarding the reliability, quality, safety and efficacy of medical technologies for assisted reproduction were assessed. This study is based on data from individual interviews that sought to explore the complexities, similarities and differences among the views and values of jurists, doctors and couples involved in in vitro fertilization treatments. It consists of a qualitative analysis on a case study. If jurists and doctors frame the status of embryos as categories of a biological, technical and/or legal nature, couples establish between themselves a variety of ontological relationships of a moral, affective and social nature. Through these, they can be represented as ethical beings, thus contrasting with the medical-legal biologization of the embryos.To the jurists, doctors and women and men who we interviewed and who shared with us their views and experiences, our sincere thanks. We also thank Helena Lima and Filomena Louro (Scientific Editing Programme, University of Minho) for the translation of the Portuguese text into English; and the revision of David George Elliff. The authors thank the Foundation for Science and Technology (Portuguese Ministry of Science, Technology and Higher Education) for the financial support for this research, through a PhD fellowship (SFRH/BD/10396/2002) and a post-doctoral fellowship (SFRH/BPD/47020/2008).info:eu-repo/semantics/publishedVersio

Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia

A comprehensive international consensus on the cytogenetic risk-group stratification of KMT2A-rearranged (KMT2A-r) pediatric acute myeloid leukemia (AML) is lacking. This retrospective (2005-2016) International Berlin-Frankfurt-Münster Study Group study on 1256 children with KMT2A-r AML aims to validate the prognostic value of established recurring KMT2A fusions and additional cytogenetic aberrations (ACAs) and to define additional, recurring KMT2A fusions and ACAs, evaluating their prognostic relevance. Compared with our previous study, 3 additional, recurring KMT2A-r groups were defined: Xq24/KMT2A::SEPT6, 1p32/KMT2A::EPS15, and 17q12/t(11;17)(q23;q12). Across 13 KMT2A-r groups, 5-year event-free survival probabilities varied significantly (21.8%-76.2%; P < .01). ACAs occurred in 46.8% of 1200 patients with complete karyotypes, correlating with inferior overall survival (56.8% vs 67.9%; P < .01). Multivariable analyses confirmed independent associations of 4q21/KMT2A::AFF1, 6q27/KMT2A::AFDN, 10p12/KMT2A::MLLT10, 10p11.2/KMT2A::ABI1, and 19p13.3/KMT2A::MLLT1 with adverse outcomes, but not those of 1q21/KMT2A::MLLT11 and trisomy 19 with favorable and adverse outcomes, respectively. Newly identified ACAs with independent adverse prognoses were monosomy 10, trisomies 1, 6, 16, and X, add(12p), and del(9q). Among patients with 9p22/KMT2A::MLLT3, the independent association of French-American-British-type M5 with favorable outcomes was confirmed, and those of trisomy 6 and measurable residual disease at end of induction with adverse outcomes were identified. We provide evidence to incorporate 5 adverse-risk KMT2A fusions into the cytogenetic risk-group stratification of KMT2A-r pediatric AML, to revise the favorable-risk classification of 1q21/KMT2A::MLLT11 to intermediate risk, and to refine the risk-stratification of 9p22/KMT2A::MLLT3 AML. Future studies should validate the associations between the newly identified ACAs and outcomes and unravel the underlying biological pathogenesis of KMT2A fusions and ACAs

Measurement of event-shape observables in Z→ℓ+ℓ− events in pp collisions at √ s=7 TeV with the ATLAS detector at the LHC

Event-shape observables measured using charged particles in inclusive $Z$-boson events are presented, using the electron and muon decay modes of the $Z$ bosons. The measurements are based on an integrated luminosity of $1.1 {\rm fb}^{-1}$ of proton--proton collisions recorded by the ATLAS detector at the LHC at a centre-of-mass energy $\sqrt{s}=7$ TeV. Charged-particle distributions, excluding the lepton--antilepton pair from the $Z$-boson decay, are measured in different ranges of transverse momentum of the $Z$ boson. Distributions include multiplicity, scalar sum of transverse momenta, beam thrust, transverse thrust, spherocity, and $\mathcal{F}$-parameter, which are in particular sensitive to properties of the underlying event at small values of the $Z$-boson transverse momentum. The Sherpa event generator shows larger deviations from the measured observables than Pythia8 and Herwig7. Typically, all three Monte Carlo generators provide predictions that are in better agreement with the data at high $Z$-boson transverse momenta than at low $Z$-boson transverse momenta and for the observables that are less sensitive to the number of charged particles in the event.Comment: 36 pages plus author list + cover page (54 pages total), 14 figures, 4 tables, submitted to EPJC, All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2014-0