Functional Analysis of N-acetylglucosaminyltransferase-I Knockdown in 2D and 3D Neuroblastoma Cell Culturess

Tumor development can be promoted/suppressed by certain N-glycans attached to proteins at the cell surface. Here we examined aberrant neuronal properties in 2D and 3D rat neuroblastoma (NB) cell cultures with different N-glycan populations. Lectin binding studies revealed that the engineered N-glycosylation mutant cell line, NB_1(-Mgat1), expressed solely oligomannose N-glycans, and verified that the parental cell line, NB_1, and a previous engineered N-glycosylation mutant, NB_1(-Mgat2), expressed significant levels of higher order N-glycans, complex and hybrid N-glycans, respectively. NB_1 grew faster than mutant cell lines in monolayer and spheroid cell cultures. A 2-fold difference in growth between NB_1 and mutants occurred much sooner in 2D cultures relative to that observed in 3D cultures. Neurites and spheroid cell sizes were reduced in mutant NB cells of 2D and 3D cultures, respectively. Cell invasiveness was highest in 2D cultures of NB_1 cells compared to that of NB_1(-Mgat1). In contrast, NB_1 spheroid cells were much less invasive relative to NB_1(-Mgat1) spheroid cells while they were more invasive than NB_1(-Mgat2). Gelatinase activities supported the ranking of cell invasiveness in various cell lines. Both palladin and HK2 were more abundant in 3D than 2D cultures. Levels of palladin, vimentin and EGFR were modified in a different manner under 2D and 3D cultures. Thus, our results support variations in the N-glycosylation pathway and in cell culturing to more resemble in vivo tumor environments can impact the aberrant cellular properties, particularly cell invasiveness, of NB

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Has Devolution Changed the 'British Policy Style'?

The term ‘policy style' simply means the way that governments make and implement policy. Yet, the term ‘British policy style' may be confusing since it has the potential to relate to British exceptionalism or European convergence. Lijphart's important contribution identifies the former. It sets up a simple distinction between policy styles in majoritarian and consensual democracies and portrays British policy-making as top down and different from a consensual European approach. In contrast, Richardson identifies a common ‘European policy style'. This suggests that although the political structures of each country vary, they share a ‘standard operating procedure' based on two factors - an incremental approach to policy and an attempt to reach a consensus with interest groups rather than impose decisions. This article extends these arguments to British politics since devolution. It questions the assumption that policy styles are diverging within Britain. Although consultation in the devolved territories may appear to be more consensual, they are often contrasted with a caricature of the UK process based on atypical examples of top-down policy-making. While there may be a different ‘feel' to participation in Scotland and Wales, a similar logic of consultation and bureaucratic accommodation exists in the UK. This suggests that, although devolution has made a difference, a British (or European) policy style can still be identified

The role of role theory in International Political Economy

This article demonstrates the benefits of using a role theory approach in the field of International Political Economy (IPE) by demonstrating the benefits of role theory relative to variants of the social constructivist paradigm, especially vis-à-vis identity based accounts of IPE. This article also documents why and how role theory has always had a home in IPE even before the constructivist revolution in the 1990s. The social interactionist dimension in the work of Herbert Mead and his notion of a general other are linked to the relational ideas of friendship and impartial spectator present in the works of the founding father of classical political economy, Adam Smith. These similar ideas about the self and their surrounding social environment is a useful starting point to locate role theory in IPE and demonstrate its analytical advantages within social constructivism. After showing the “forgotten” place role theory has always had in IPE, the article illustrates the potential of using a role theory approach within the field of IPE through an illustrative analysis of the Greek economic crisis

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Specialization training in Malawi: A qualitative study on the perspectives of medical students graduating from the University of Malawi College of Medicine

Background: There is a critical shortage of healthcare workers in sub-Saharan Africa, and Malawi has one of the lowest physician densities in the region. One of the reasons for this shortage is inadequate retention of medical school graduates, partly due to the desire for specialization training. The University of Malawi College of Medicine has developed specialty training programs, but medical school graduates continue to report a desire to leave the country for specialization training. To understand this desire, we studied medical students' perspectives on specialization training in Malawi. Methods. We conducted semi-structured interviews of medical students in the final year of their degree program. We developed an interview guide through an iterative process, and recorded and transcribed all interviews for analysis. Two independent coders coded the manuscripts and assessed inter-coder reliability, and the authors used an "editing approach" to qualitative analysis to identify and categorize themes relating to the research aim. The University of Pittsburgh Institutional Review Board and the University of Malawi College of Medicine Research and Ethics Committee approved this study and authors obtained written informed consent from all participants. Results: We interviewed 21 medical students. All students reported a desire for specialization training, with 12 (57%) students interested in specialties not currently offered in Malawi. Students discussed reasons for pursuing specialization training, impressions of specialization training in Malawi, reasons for staying or leaving Malawi to pursue specialization training and recommendations to improve training. Conclusions: Graduating medical students in Malawi have mixed views of specialization training in their own country and still desire to leave Malawi to pursue further training. Training institutions in sub-Saharan Africa need to understand the needs of the country's healthcare workforce and the needs of their graduating medical students to be able to match opportunities and retain graduating students. © 2014 Sawatsky et al.; licensee BioMed Central Ltd

Quasispecies Theory and the Behavior of RNA Viruses

A large number of medically important viruses, including HIV, hepatitis C virus, and influenza, have RNA genomes. These viruses replicate with extremely high mutation rates and exhibit significant genetic diversity. This diversity allows a viral population to rapidly adapt to dynamic environments and evolve resistance to vaccines and antiviral drugs. For the last 30 years, quasispecies theory has provided a population-based framework for understanding RNA viral evolution. A quasispecies is a cloud of diverse variants that are genetically linked through mutation, interact cooperatively on a functional level, and collectively contribute to the characteristics of the population. Many predictions of quasispecies theory run counter to traditional views of microbial behavior and evolution and have profound implications for our understanding of viral disease. Here, we discuss basic principles of quasispecies theory and describe its relevance for our understanding of viral fitness, virulence, and antiviral therapeutic strategy