Inverse Mapping of Polarised Optical Emission from Pulsars : Basic Formulation and Determination of Emission Altitude

We present an inverse mapping approach to determining the emission height of the optical photons from pulsars, which is directly constrained by empirical data. The model discussed is for the case of the Crab pulsar. Our method, using the optical Stokes parameters, determines the most likely geometry for emission including magnetic field inclination angle ($\alpha$), observers line of sight angle ($\chi$) and emission height. We discuss the computational implementation of the approach, along with any physical assumptions made. We find that the most likely emission altitude is at 20% of the light cylinder radius above the stellar surface, in the open field region. We also present a general treatment of the expected polarisation from synchrotron source with a truncated power law spectrum of particles.Comment: 17 pages 16 figures; accepted for publication in MNRA

Creating Creative Technologists: playing with(in) education

Since the industrial revolution, the organization of knowledge into distinct scientific, technical or creative categories has resulted in educational systems designed to produce and validate particular occupations. The methods by which students are exposed to different kinds of knowledge are critical in creating and reproducing individual, professional or cultural identities. (“I am an Engineer. You are an Artist”). The emergence of more open, creative and socialised technologies generates challenges for discipline-based education. At the same time, the term “Creative Technologies” also suggests a new occupational category (“I am a Creative Technologist”). This chapter presents a case-study of an evolving ‘anti-disciplinary’ project-based degree that challenges traditional degree structures to stimulate new forms of connective, imaginative and explorative learning, and to equip students to respond to a changing world. Learning is conceived as an emergent process; self-managed by students through critique and open peer review. We focus on ‘playfulness’ as a methodology for achieving multi-modal learning across the boundaries of art, design, computer science, engineering, games and entrepreneurship. In this new cultural moment, playfulness also re-frames the institutional identities of teacher and learner in response to new expectations for learning

On the Importance of Countergradients for the Development of Retinotopy: Insights from a Generalised Gierer Model

During the development of the topographic map from vertebrate retina to superior colliculus (SC), EphA receptors are expressed in a gradient along the nasotemporal retinal axis. Their ligands, ephrin-As, are expressed in a gradient along the rostrocaudal axis of the SC. Countergradients of ephrin-As in the retina and EphAs in the SC are also expressed. Disruption of any of these gradients leads to mapping errors. Gierer's (1981) model, which uses well-matched pairs of gradients and countergradients to establish the mapping, can account for the formation of wild type maps, but not the double maps found in EphA knock-in experiments. I show that these maps can be explained by models, such as Gierer's (1983), which have gradients and no countergradients, together with a powerful compensatory mechanism that helps to distribute connections evenly over the target region. However, this type of model cannot explain mapping errors found when the countergradients are knocked out partially. I examine the relative importance of countergradients as against compensatory mechanisms by generalising Gierer's (1983) model so that the strength of compensation is adjustable. Either matching gradients and countergradients alone or poorly matching gradients and countergradients together with a strong compensatory mechanism are sufficient to establish an ordered mapping. With a weaker compensatory mechanism, gradients without countergradients lead to a poorer map, but the addition of countergradients improves the mapping. This model produces the double maps in simulated EphA knock-in experiments and a map consistent with the Math5 knock-out phenotype. Simulations of a set of phenotypes from the literature substantiate the finding that countergradients and compensation can be traded off against each other to give similar maps. I conclude that a successful model of retinotopy should contain countergradients and some form of compensation mechanism, but not in the strong form put forward by Gierer

HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results

Transition Metal and Main Group Complexes Stabilized by Dispersion Energy Donor (DED) Ligand Derivatives of 1-bromo-2,4,6-tricyclohexylbenzene AND Ni(I) and Ni(II) Bis(trimethylsilyl)amides Obtained in Pursuit of the Elusive Structure of Ni{N(SiMe3)2}2

The purpose of the first part of this thesis is to describe how dispersion energy donor ligands derived from 1-bromo-2,4,6-tricyclohexylbenzene (BrC6H2-2,4,6-Cy3) can effect the stabilization of low-valent transition metal and main group compounds. Thus, reactions of 2,4,6-tricyclohexylphenol with [M{N(SiMe3)2}2]2 (M = Mn(II), Fe(II), Co(II)) at room temperature in hexanes afforded the dimeric species [M(OC6H2-2,4,6-Cy3)2]2 (M= Mn(II), Fe(II), Co(II)) in high yield as crystalline species. Use of the sterically similar ligand HOC6H3-2,6-Pri2 (Pri = isopropyl) gave trimeric species [M(OC6H3-2,6-Pri2)2]3 (M = Fe(II), Co(II)) and implicates the dispersion energy donor capabilities of the phenol HOC6H2-2,4,6-Cy3 as the driving force for the formation of dimeric rather than trimeric species. While the Mn(II) and Fe(II) aryloxides are thermally stable, the corresponding Co(II) derivative rearranges to form a dimeric Co(II) semiquinone complex when heated under dynamic vacuum to temperatures above ca. 180 oC. Analogous reactions of HOC6H2-2,4,6-Cy3 with main group bis(trimethylsilyl)amides M{N(SiMe3)2}2 (M = Ge(II), Sn(II), and Pb(II)) gave the dimeric tetrel(II) aryloxides [M(OC6H2-2,4,6-Cy3)2]2. For Ge(II), stirring the reaction for longer than ca. 30 minutes at room temperature in hexane allows the isolation of the rearranged Ge6O8 cluster [Ge6(μ3-O)4(μ2-OC6H2-2,4,6-Cy3)4](NH3)0.5 which traps in situ generated ammonia in non-coordinating positions through the dispersion energy donor interactions provided by the cyclohexyl groups of -OC6H2-2,4,6-Cy3.The arylthiolates [M(SC6H2-2,4,6-Cy3)2]2 (M = Ge(II), Sn(II), Pb(II)) were synthesized in an analogous manner to the tetrel(II) aryloxides by the addition of HSC6H2-2,4,6-Cy3 to the M(II) bis(trimethylsilyl)amides. They are the first examples of dimeric M(II) arylthiolates of Ge(II) and Sn(II). Also, the Pb(II) species is the first arylthiolate isolable in the absence of donor ligands or Lewis bases. Previous attempts to obtain a Ge(II) arylthiolate using the thiol HSC6H2-2,4,6-Pri3 gave the Ge(IV) hydride HGe(SC6H2-2,4,6-Pri3)3. DFT calculations revealed that an increase in the dispersion energy stabilization provided by -SC6H2-2,4,6-Cy3 in the species [Ge(SC6H2-2,4,6-Cy3)2]2 prevents the formation of a Ge(IV) hydride analogous to that observed when the thiolato ligand -SC6H2-2,4,6-Pri3 was used. A concentration dependent monomer-dimer equilibrium is evident in benzene solutions of [Ge(SC6H2-2,4,6-Cy3)2]2, despite the large increase in dispersion energy stabilization. The Ge(II) and Sn(II) arylthiolates are not isostructural with their aryloxo congeners and have a cis arrangement of the ligands in the solid state. In contrast, the Pb(II) thiolate is isostructural with the Pb(II) aryloxo congener and crystallizes with a trans arrangement of the -SC6H2-2,4,6-Cy3 ligands. The final section of this thesis provides detail on the synthesis and isolation of Ni(I) and Ni(II) bis(trimethylsilyl)amides that were isolated during pursuit of the solid-state structure of the highly unstable species Ni{N(SiMe3)2}2. The use of the bis(trimethylsilyl)amide K{N(SiMe3)2} as transfer agent was reported to give intractable solids when reacted with NiCl2 in diethyl ether. This prompted a reinvestigation of the use of this transfer agent in the synthesis and isolation of new Ni(II) bis(trimethylsilyl)amides. The reaction of K{N(SiMe3)2} with NiI2 in Et2O gave the three new complexes [K][Ni{N(SiMe3)2}3], [K][Ni{N(SiMe3)2}2], and [K(THF)2][Ni{N(SiMe3)2}3]. The use of NiCl2(DME) (DME = 1,2-dimethoxyethane) instead of NiI2 as the nickel source gave [K(DME)][Ni2{N(SiMe3)2}3]. The isolation of the Ni(I) complexes [K][Ni{N(SiMe3)2}2] and [K(DME)][Ni2{N(SiMe3)2}3] highlights both the tendency for K{N(SiMe3)2} to function as a reducing agent and the sensitivity and unpredictable nature of the Ni(II) bis(trimethylsilyl)amido derivatives. Introduction of adventitious O2 to solutions of [K][Ni{N(SiMe3)2}2] gave the first nickel inverse crown ether (ICE) species [K2][O(Ni{N(SiMe3)2}2)2], which is one of just four known ICE complexes of the 3d metals. While the Ni(I) species can be isolated as crystalline solids from the disproportionation of the Ni(II) species, the corresponding Ni(III) products were not readily isolable under the employed reaction conditions

History of adversity, health and psychopathology among prisoners: comparison between men and women

Adversity in childhood, risk behaviors and psychopathology are highly prevalent phenomena in inmate populations and have a strong impact on health. Knowing the differences in these variables between the sexes is most important in order to develop appropriate intervention strategies in a prison context. By administering the Socio-demographic and Life History Questionnaire and the Brief Symptoms Inventory, we sought to characterize adverse childhood experiences and relate them to risk behaviors and to psychopathological symptoms, and study the differences between the 65 male and 42 female detainees in Portuguese prison establishments. Men and women report a complex web of adversity in childhood. In a range of ten possible categories, a medium value of 5.05 (DP = 2.63) in total adversity for women and 2.63 (DP = 2.18) for men was encountered, with the prevalence being significantly higher within the female population (Z = -4.33; p = .000). A high prevalence of risk behaviors and psychopathological symptoms was found in both groups, the latter being higher among females. We concluded that the differences between men and women calls for in depth studies in order to provide guidelines for intervention projects in specific populations.Adversidade na infância, comportamentos de risco e psicopatologia são fenómenos muito prevalentes na população reclusa e com forte impacto na saúde. Conhecer as diferenças entre sexos, no que diz respeito a tais variáveis, é de elevada importância no sentido de adequar estraté- gias de intervenção em contexto prisional. Utilizando o Questionário Sociodemográfico e Histó- ria de Vida, o Questionário de Adversidade na Infância e o Brief Symptons Inventory, procuramos caracterizar a adversidade na infância, os comportamentos de risco e as dimensões psicopatológicas, e averiguar as diferenças entre 65 homens e 42 mulheres reclusos em estabelecimentos prisionais Portugueses. Homens e mulheres relatam um quadro complexo de adversidade na infância. Num total possível de dez categorias, verificamos uma média de adversidade total de 5.05 (DP = 2.63) para as mulheres e de 2.63 (DP = 2.18) para os homens, sendo a prevalência significativamente mais elevada junto da população feminina (Z = -4.33; p = .000). Foi ainda encontrada uma elevada prevalência de comportamentos de risco e de sintomatologia psicopatológica em ambos os grupos, sendo esta última superior nas mulheres. Concluímos que as diferenças entre sexos devem ser estudadas para guiarem a adequação dos projetos

Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system

Previous studies have suggested that risk of psychotic events may be increased in children exposed to methylphenidate (MPH). However, this risk has not been fully examined and the possibility of confounding factors has not been excluded. Patients aged 6-19 years who received at least one MPH prescription were identified using Hong Kong population-based electronic medical records on the Clinical Data Analysis & Reporting System (2001-2014). Using the self-controlled case series design, relative incidence of psychotic events was calculated comparing periods when patients were exposed to MPH with non-exposed periods. Of 20 586 patients prescribed MPH, 103 had an incident psychotic event; 72 (69.9%) were male and 31 (30.1%) female. The mean age at commencement of observation was 6.95 years and the mean follow-up per participant was 10.16 years. On average, each participant was exposed to MPH for 2.17 years. The overall incidence of psychotic events during the MPH exposure period was 6.14 per 10 000 patient-years. No increased risk was found during MPH exposed compared to non-exposed periods (incidence rate ratio (IRR) 1.02 (0.53-1.97)). However, an increased risk was found during the pre-exposure period (IRR 4.64 (2.17-9.92)). Results were consistent across all sensitivity analyses. This study does not support the hypothesis that MPH increases risk of incident psychotic events. It does indicate an increased risk of psychotic events prior to the first prescription of MPH, which may be due to an association between psychotic events and the behavioural and attentional symptoms that led to psychiatric assessment and initiation of MPH treatment

Cold atmospheric plasma induces ATP-dependent endocytosis of nanoparticles and synergistic U373MG cancer cell death

Gold nanoparticles (AuNP) have potential as both diagnostic and therapeutic vehicles. However, selective targeting and uptake in cancer cells remains challenging. Cold atmospheric plasma (CAP) can be combined with AuNP to achieve synergistic anti-cancer cytotoxicity. To explore synergistic mechanisms, we demonstrate both rate of AuNP uptake and total amount accumulated in U373MG Glioblastoma multiforme (GBM) cells are significantly increased when exposed to 75 kV CAP generated by dielectric barrier discharge. No significant changes in the physical parameters of AuNP were caused by CAP but active transport mechanisms were stimulated in cells. Unlike many other biological effects of CAP, long-lived reactive species were not involved, and plasma-activated liquids did not replicate the effect. Chemical effects induced by direct and indirect exposure to CAP appears the dominant mediator of enhanced uptake. Transient physical alterations of membrane integrity played a minor role. 3D-reconstruction of deconvoluted confocal images confirmed AuNP accumulation in lysosomes and other acidic vesicles, which will be useful for future drug delivery and diagnostic strategies. Toxicity of AuNP significantly increased by 25-fold when combined with CAP. Our data indicate that direct exposure to CAP activates AuNP-dependent cytotoxicity by increasing AuNP endocytosis and trafficking to lysosomes in U373MG cells

Shared neural representations of tactile roughness intensities by somatosensation and touch observation using an associative learning method

Previous human fMRI studies have reported activation of somatosensory areas not only during actual touch, but also during touch observation. However, it has remained unclear how the brain encodes visually evoked tactile intensities. Using an associative learning method, we investigated neural representations of roughness intensities evoked by (a) tactile explorations and (b) visual observation of tactile explorations. Moreover, we explored (c) modality-independent neural representations of roughness intensities using a cross-modal classification method. Case (a) showed significant decoding performance in the anterior cingulate cortex (ACC) and the supramarginal gyrus (SMG), while in the case (b), the bilateral posterior parietal cortices, the inferior occipital gyrus, and the primary motor cortex were identified. Case (c) observed shared neural activity patterns in the bilateral insula, the SMG, and the ACC. Interestingly, the insular cortices were identified only from the cross-modal classification, suggesting their potential role in modality-independent tactile processing. We further examined correlations of confusion patterns between behavioral and neural similarity matrices for each region. Significant correlations were found solely in the SMG, reflecting a close relationship between neural activities of SMG and roughness intensity perception. The present findings may deepen our understanding of the brain mechanisms underlying intensity perception of tactile roughness

Investor heterogeneity and the cross-section of U.K. investment trust performance

We use the upper and lower bounds derived by Ferson and Lin (2010) to examine the impact of investor heterogeneity on the performance of U.K. investment trusts relative to alternative linear factor models. We find using the upper bounds that investor heterogeneity has an important impact for nearly all investment trusts. The upper bounds are large in economic terms and significantly different from zero. We find no evidence of any trusts where all investors agree on the sign of performance beyond what we expect by chance. Using the lower bound, we find that trusts with a larger disagreement about trust performance have a weaker relation between the trust premium and past Net Asset Value (NAV) performance