D-optimal designs via a cocktail algorithm

A fast new algorithm is proposed for numerical computation of (approximate) D-optimal designs. This "cocktail algorithm" extends the well-known vertex direction method (VDM; Fedorov 1972) and the multiplicative algorithm (Silvey, Titterington and Torsney, 1978), and shares their simplicity and monotonic convergence properties. Numerical examples show that the cocktail algorithm can lead to dramatically improved speed, sometimes by orders of magnitude, relative to either the multiplicative algorithm or the vertex exchange method (a variant of VDM). Key to the improved speed is a new nearest neighbor exchange strategy, which acts locally and complements the global effect of the multiplicative algorithm. Possible extensions to related problems such as nonparametric maximum likelihood estimation are mentioned.Comment: A number of changes after accounting for the referees' comments including new examples in Section 4 and more detailed explanations throughou

Thermodynamic and Tunneling Density of States of the Integer Quantum Hall Critical State

We examine the long wave length limit of the self-consistent Hartree-Fock approximation irreducible static density-density response function by evaluating the charge induced by an external charge. Our results are consistent with the compressibility sum rule and inconsistent with earlier work that did not account for consistency between the exchange-local-field and the disorder potential. We conclude that the thermodynamic density of states is finite, in spite of the vanishing tunneling density of states at the critical energy of the integer quantum Hall transition.Comment: 5 pages, 4 figures, minor revisions, published versio

The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration

Integrin β3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3-dependent adhesome. We show that depletion of β3-integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3-integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2-driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3-integrin levels are reduced

Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia

Rationale: Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and interpretation have not been standardized. Objectives: Touse a standard protocol formeasuringnNOtoestablishadiseasespecific cutoff value at one site, and then validate at six other sites. Methods: At the lead site, nNO was prospectively measured in individuals later confirmed to have PCD by ciliary ultrastructural defects (n = 143) or DNAH11 mutations (n = 6); and in 78 healthy and 146 disease control subjects, including individuals with asthma (n = 37), cystic fibrosis (n = 77), and chronic obstructive pulmonary disease (n = 32). A disease-specific cutoff value was determined, using generalized estimating equations (GEEs). Six other sites prospectively measured nNO in 155 consecutive individuals enrolled for evaluation for possible PCD. Measurements and Main Results: At the lead site, nNO values in PCD (mean6standard deviation, 20.7624.1 nl/min; range, 1.5-207.3 nl/min) only rarely overlapped with the nNO values of healthy control subjects (304.6 6 118.8; 125.5-867.0 nl/min), asthma (267.8 6 103.2; 125.0-589.7 nl/min), or chronic obstructive pulmonary disease (223.7 6 87.1; 109.7-449.1 nl/min); however, therewas overlapwith cystic fibrosis (134.0673.5; 15.6-386.1 nl/min). The disease-specific nNOcutoff valuewas defined at 77 nl/minute (sensitivity, 0.98; specificity, .0.999). At six other sites, this cutoff identified 70 of the 71 (98.6%) participants with confirmed PCD. Conclusions: Using a standardized protocol in multicenter studies, nNO measurement accurately identifies individuals with PCD, and supports its usefulness as a test to support the clinical diagnosis of PCD

Using isotopic dilution to assess chemical extraction of labile Ni, Cu, Zn, Cd and Pb in soils

Chemical extractants used to measure labile soil metal must ideally select for and solubilise the labile fraction, with minimal solubilisation of non-labile metal. We assessed four extractants (0.43 M HNO3, 0.43 M CH3COOH, 0.05 M Na2H2EDTA and 1 M CaCl2) against these requirements. For soils contaminated by contrasting sources, we compared isotopically exchangeable Ni, Cu, Zn, Cd and Pb (EValue, mg kg-1), with the concentrations of metal solubilised by the chemical extractants (MExt, mg kg-1). Crucially, we also determined isotopically exchangeable metal in the soil–extractant systems (EExt, mg kg-1). Thus ‘EExt - EValue’ quantifies the concentration of mobilised non-labile metal, while ‘EExt - MExt’ represents adsorbed labile metal in the presence of the extractant. Extraction with CaCl2 consistently underestimated EValue for Ni, Cu, Zn and Pb, while providing a reasonable estimate of EValue for Cd. In contrast, extraction with HNO3 both consistently mobilised non-labile metal and overestimated the EValue. Extraction with CH3COOH appeared to provide a good estimate of EValue for Cd; however, this was the net outcome of incomplete solubilisation of labile metal, and concurrent mobilisation of non-labile metal by the extractant (MExt EValue). The Na2H2EDTA extractant mobilised some non-labile metal in three of the four soils, but consistently solubilised the entire labile fraction for all soil-metal combinations (MExt ≈ EExt). Comparison of EValue, MExt and EExt provides a rigorous means of assessing the underlying action of soil chemical extraction methods and could be used to refine long-standing soil extraction methodologies

Couplings of light I=0 scalar mesons to simple operators in the complex plane

The flavour and glue structure of the light scalar mesons in QCD are probed by studying the couplings of the I=0 mesons $\sigma(600)$ and $f_0(980)$ to the operators $\bar{q}q$, $\alpha_s G^2$ and to two photons. The Roy dispersive representation for the $\pi\pi$ amplitude $t_0^0(s)$ is used to determine the pole positions as well as the residues in the complex plane. On the real axis, $t_0^0$ is constrained to solve the Roy equation together with elastic unitarity up to the K\Kbar threshold leading to an improved description of the $f_0(980)$. The problem of using a two-particle threshold as a matching point is discussed. A simple relation is established between the coupling of a scalar meson to an operator $j_S$ and the value of the related pion form-factor computed at the resonance pole. Pion scalar form-factors as well as two-photon partial-wave amplitudes are expressed as coupled-channel Omn\`es dispersive representations. Subtraction constants are constrained by chiral symmetry and experimental data. Comparison of our results for the $\bar{q}q$ couplings with earlier determinations of the analogous couplings of the lightest I=1 and $I=1/2$ scalar mesons are compatible with an assignment of the $\sigma$, $\kappa$, $a_0(980)$, $f_0(980)$ into a nonet. Concerning the gluonic operator $\alpha_s G^2$ we find a significant coupling to both the $\sigma$ and the $f_0(980)$.Comment: 31 pages, 5 figure

A mathematical framework for contact detection between quadric and superquadric surfaces

The calculation of the minimum distance between surfaces plays an important role in computational mechanics, namely, in the study of constrained multibody systems where contact forces take part. In this paper, a general rigid contact detection methodology for non-conformal bodies, described by ellipsoidal and superellipsoidal surfaces, is presented. The mathematical framework relies on simple algebraic and differential geometry, vector calculus, and on the C2 continuous implicit representations of the surfaces. The proposed methodology establishes a set of collinear and orthogonal constraints between vectors defining the contacting surfaces that, allied with loci constraints, which are specific to the type of surface being used, formulate the contact problem. This set of non-linear equations is solved numerically with the Newton-Raphson method with Jacobian matrices calculated analytically. The method outputs the coordinates of the pair of points with common normal vector directions and, consequently, the minimum distance between both surfaces. Contrary to other contact detection methodologies, the proposed mathematical framework does not rely on polygonal-based geometries neither on complex non-linear optimization formulations. Furthermore, the methodology is extendable to other surfaces that are (strictly) convex, interact in a non-conformal fashion, present an implicit representation, and that are at least C2 continuous. Two distinct methods for calculating the tangent and binormal vectors to the implicit surfaces are introduced: (i) a method based on the Householder reflection matrix; and (ii) a method based on a square plate rotation mechanism. The first provides a base of three orthogonal vectors, in which one of them is collinear to the surface normal. For the latter, it is shown that, by means of an analogy to the referred mechanism, at least two non-collinear vectors to the normal vector can be determined. Complementarily, several mathematical and computational aspects, regarding the rigid contact detection methodology, are described. The proposed methodology is applied to several case tests involving the contact between different (super)ellipsoidal contact pairs. Numerical results show that the implemented methodology is highly efficient and accurate for ellipsoids and superellipsoids.Fundação para a Ciência e a Tecnologia (FCT

Soccer and homosexuality: the conflicts that lie within the affective game of the coach-adolescent athlete relationship

Discussions regarding homosexuality within a sports context are mediated by emotional nuances, especially in the world of soccer, where practitioners are required to have attributes such as strength, masculinity and aggressiveness. As a consequence, this work aimed to analyze the symbolic representation of homosexual relationships between adolescent soccer players and their coaches; and, furthermore, to understand the intention behind homoerotic relationships that are established between members of the management team and its players. In this study, researchers used the life history methodology, with participation from three adolescent athletes, ages 14, 15 and 16, and three former athletes, ages 26, 28 and 45, who we called speakers. Based on the collection and analysis of research participants’ testimonies, homosexual relations were found to have occurred between athletes and coaches, or between athletes and other members of the management team, as a part of a “social contract” that is exclusively linked to their professional objectives. These relationships appear to be purely objective; authentic affective links are absent, due apparently to the transient nature of the athletes in these groups. Too, this context is usually marked by the athlete’s physical and emotional vulnerability, and the agreements he makes within this context are accompanied with moral dilemmas, because such adolescents idealize the coach as a paternal archetype.“Futebol e homossexualidade: Os conflitos que se encontram dentro do jogo afetivo da relação treinador-atleta adolescente.” As discussões a respeito da homossexualidade no contexto esportivo são mediadas por nuanças emocionais, especialmente no mundo do futebol que exige de seus praticantes atributos de força, virilidade e agressividade. Por este motivo este trabalho teve como objetivos diagnosticar existência de relações homossexuais entre atletas adolescentes da modalidade de futebol e seus técnicos e sua representação simbólica e ainda, compreender a intencionalidade das relações homoafetivas que se estabelecem entre componentes da equipe diretiva e os jogadores. Esta pesquisa é de natureza qualitativa e a técnica adotada foi a “história de vida” e a participação de três atletas adolescentes em atividade, com idade de 14, 15 e 16 anos e três ex-atletas profissionais, com idades 26, 28 e 45 anos serviram de base metodológica. A partir da análise e tratamento dos depoimentos verificou-se que ocorreram relações homossexuais nas categorias de base envolvendo técnico e atleta, ou com outros membros da equipe diretiva, como parte dos contratos sociais, ligados exclusivamente a objetivos profissionais. Estas relações parecem ser puramente objetais, não parecendo existir vínculos afetivos duradouros, aparentemente, devido à natureza transitória de atletas nesses grupos. Também, nesses ambientes, muitas vezes marcados pela vulnerabilidade física e emocional dos atletas, os acertos para as relações homossexuais são permeadas por dilemas morais, tendo em vista que os atletas adolescentes idealizam o treinador como o arquétipo paterno ideal.“El fútbol y la homosexualidad: Los conflictos que se encuentran dentro del juego afectivo de la relación atleta-entrenador de los adolescentes.” Las discusiones sobre la homosexualidad en contexto deportivo están mediadas por matices emocionales, sobre todo en el mundo del fútbol que exige a sus jugadores atributos como la fuerza, la virilidad y los jugadores. En este estudio, los investigadores utilizaron la metodología de la historia de vida, con la participación de tres atletas adolescentes, con 14, 15 y 16 años, y tres ex atletas con 26, 28 y 45 años, que llamamos ‘oradores’. Basado en la recogida y análisis de testimonios de participantes en la investigación, se encontró que las relaciones homosexuales que se han producido entre los atletas y entrenadores, o entre atletas y otros miembros del equipo de gestión, son como parte de un “contrato social” que está vinculado exclusivamente a sus objetivos profesionales. Estas relaciones parecen ser solamente como un objeto; porque a veces no hay vínculos afectivos auténticos, debido aparentemente a la naturaleza transitoria de los atletas en estos grupos. Demasiado, este contexto es generalmente marcado por la vulnerabilidad física y emocional del deportista, y los acuerdos que hace dentro de este contexto se acompañan con dilemas morales, debido a que tales adolescentes idealizan el entrenador como un arquetipo paterno. la agresividad. Por lo tanto, este estudio tuvo como objetivo diagnosticar la existencia de relaciones homosexuales entre adolescentes atletas de fútbol y sus entrenadores y la representación simbólica de estas relaciones. También comprender la intencionalidad de las relaciones homoafetivas que se intercambian entre algunos componentes del equipo directivo y(undefined

De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy with Hydrocephalus and Randomization of Left/Right Body Asymmetry

Hydrocephalus is one of the most prevalent form of developmental central nervous system (CNS) malformations. Cerebrospinal fluid (CSF) flow depends on both heartbeat and body movement. Furthermore, it has been shown that CSF flow within and across brain ventricles depends on cilia motility of the ependymal cells lining the brain ventricles, which play a crucial role to maintain patency of the narrow sites of CSF passage during brain formation in mice. Using whole-exome and whole-genome sequencing, we identified an autosomal-dominant cause of a distinct motile ciliopathy related to defective ciliogenesis of the ependymal cilia in six individuals. Heterozygous de novo mutations in FOXJ1, which encodes a well-known member of the forkhead transcription factors important for ciliogenesis of motile cilia, cause a motile ciliopathy that is characterized by hydrocephalus internus, chronic destructive airway disease, and randomization of left/right body asymmetry. Mutant respiratory epithelial cells are unable to generate a fluid flow and exhibit a reduced number of cilia per cell, as documented by high-speed video microscopy (HVMA), transmission electron microscopy (TEM), and immunofluorescence analysis (IF). TEM and IF demonstrate mislocalized basal bodies. In line with this finding, the focal adhesion protein PTK2 displays aberrant localization in the cytoplasm of the mutant respiratory epithelial cells