Extracellular ionic locks determine variation in constitutive activity and ligand potency between species orthologs of the free fatty acid receptors FFA2 and FFA3

Free fatty acid receptors 2 and 3 (FFA2 and FFA3) are G protein-coupled receptors for short chain free fatty acids (SCFAs). They respond to the same set of endogenous ligands but with distinct rank-order of potency, such that acetate (C2) has been described as FFA2 selective while propionate (C3) is non-selective. Although C2 was confirmed to be selective for human FFA2 over FFA3, this ligand was not selective between the mouse orthologs. Moreover, although C3 was indeed not selective between the human orthologs it displayed clear selectivity for mouse FFA3 over mouse FFA2. This altered selectivity to C2 and C3 resulted from broad differences in SCFAs potency at the mouse orthologs. In studies to define the molecular basis for these observations marked variation in ligand-independent, constitutive activity was identified. The orthologs with higher potency for the SCFAs, human FFA2 and mouse FFA3, displayed high constitutive activity while the orthologs with lower potency for the agonist ligands, mouse FFA2 and human FFA3, did not. Sequence alignments of the 2nd extracellular loop identified single negatively charged residues in FFA2 and FFA3 not conserved between species and predicted to form ionic lock interactions with arginine residues within the FFA2 or FFA3 agonist binding pocket to regulate constitutive activity and SCFA potency. Reciprocal mutation of these residues between species orthologs resulted in the induction (or repression) of constitutive activity, and in most cases also yielded corresponding changes in SCFA potency.

Magnetic switching of ferroelectric domains at room temperature in multiferroic PZTFT

Single-phase magnetoelectric multiferroics are ferroelectric materials that display some form of magnetism. In addition, magnetic and ferroelectric order parameters are not independent of one another. Thus, the application of either an electric or magnetic field simultaneously alters both the electrical dipole configuration and the magnetic state of the material. The technological possibilities that could arise from magnetoelectric multiferroics are considerable and a range of functional devices has already been envisioned. Realising these devices, however, requires coupling effects to be significant and to occur at room temperature. Although such characteristics can be created in piezoelectric-magnetostrictive composites, to date they have only been weakly evident in single-phase multiferroics. Here in a newly discovered room temperature multiferroic, we demonstrate significant room temperature coupling by monitoring changes in ferroelectric domain patterns induced by magnetic fields. An order of magnitude estimate of the effective coupling coefficient suggests a value of ~1 × 10-7 sm-1.

Auditory gist: Recognition of very short sounds from timbre cues

Sounds such as the voice or musical instruments can be recognized on the basis of timbre alone. Here, sound recognition was investigated with severely reduced timbre cues. Short snippets of naturally recorded sounds were extracted from a large corpus. Listeners were asked to report a target category (e.g., sung voices) among other sounds (e.g., musical instruments). All sound categories covered the same pitch range, so the task had to be solved on timbre cues alone. The minimum duration for which performance was above chance was found to be short, on the order of a few milliseconds, with the best performance for voice targets. Performance was independent of pitch and was maintained when stimuli contained less than a full waveform cycle. Recognition was not generally better when the sound snippets were time-aligned with the sound onset compared to when they were extracted with a random starting time. Finally, performance did not depend on feedback or training, suggesting that the cues used by listeners in the artificial gating task were similar to those relevant for longer, more familiar sounds. The results show that timbre cues for sound recognition are available at a variety of time scales, including very short ones.

From Beijing with love: The global dimension of Bertolucci’s The Last Emperor

Famous for being the first foreign feature film that obtained permission to shoot in the Forbidden City, The Last Emperor (1987) is also one of the most ambitious and expensive independent productions of its time, awarded four Golden Globes and nine Academy Awards, including Best Picture. In addition, The Last Emperor can be considered as one of the first attempts of cinematic collaboration between West and East, in a period of cultural and economic transformations witnessed by China. This article aims to offer an overview of the production history of The Last Emperor, focusing on the co-production collaborations and the outcomes of a western auteur’s gaze on Chinese history. Questions of Orientalism, travel narrative and critical reception are taken into account in order to engage with the transnational implications of Bertolucci’s film and the western fascination with China.

Adherence to treatment in children and adolescents with cystic fibrosis: a cross-sectional, multi-method study investigating the influence of beliefs about treatment and parental depressive symptoms

BACKGROUND: Adherence to treatment is often reported to be low in children with cystic fibrosis. Adherence in cystic fibrosis is an important research area and more research is needed to better understand family barriers to adherence in order for clinicians to provide appropriate intervention. The aim of this study was to evaluate adherence to enzyme supplements, vitamins and chest physiotherapy in children with cystic fibrosis and to determine if any modifiable risk factors are associated with adherence.

METHODS: A sample of 100 children (≤18 years) with cystic fibrosis (44 male; median [range] 10.1 [0.2-18.6] years) and their parents were recruited to the study from the Northern Ireland Paediatric Cystic Fibrosis Centre. Adherence to enzyme supplements, vitamins and chest physiotherapy was assessed using a multi-method approach including; Medication Adherence Report Scale, pharmacy prescription refill data and general practitioner prescription issue data. Beliefs about treatments were assessed using refined versions of the Beliefs about Medicines Questionnaire-specific. Parental depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale.

RESULTS: Using the multi-method approach 72% of children were classified as low-adherers to enzyme supplements, 59% low-adherers to vitamins and 49% low-adherers to chest physiotherapy. Variations in adherence were observed between measurement methods, treatments and respondents. Parental necessity beliefs and child age were significant independent predictors of child adherence to enzyme supplements and chest physiotherapy, but parental depressive symptoms were not found to be predictive of adherence.

CONCLUSIONS: Child age and parental beliefs about treatments should be taken into account by clinicians when addressing adherence at routine clinic appointments. Low adherence is more likely to occur in older children, whereas, better adherence to cystic fibrosis therapies is more likely in children whose parents strongly believe the treatments are necessary. The necessity of treatments should be reinforced regularly to both parents and children.

Genome analysis of a simultaneously predatory and prey-independent, novel Bdellovibrio bacteriovorus from the River Tiber, supports in silico predictions of both ancient and recent lateral gene transfer from diverse bacteria

BACKGROUND: Evolution equipped Bdellovibrio bacteriovorus predatory bacteria to invade other bacteria, digesting and replicating, sealed within them thus preventing nutrient-sharing with organisms in the surrounding environment. Bdellovibrio were previously described as "obligate predators" because only by mutations, often in gene bd0108, are 1 in ~1x10(7) of predatory lab strains of Bdellovibrio converted to prey-independent growth. A previous genomic analysis of B. bacteriovorus strain HD100 suggested that predatory consumption of prey DNA by lytic enzymes made Bdellovibrio less likely than other bacteria to acquire DNA by lateral gene transfer (LGT). However the Doolittle and Pan groups predicted, in silico, both ancient and recent lateral gene transfer into the B. bacteriovorus HD100 genome.

RESULTS: To test these predictions, we isolated a predatory bacterium from the River Tiber- a good potential source of LGT as it is rich in diverse bacteria and organic pollutants- by enrichment culturing with E. coli prey cells. The isolate was identified as B. bacteriovorus and named as strain Tiberius. Unusually, this Tiberius strain showed simultaneous prey-independent growth on organic nutrients and predatory growth on live prey. Despite the prey-independent growth, the homolog of bd0108 did not have typical prey-independent-type mutations. The dual growth mode may reflect the high carbon content of the river, and gives B. bacteriovorus Tiberius extended non-predatory contact with the other bacteria present. The HD100 and Tiberius genomes were extensively syntenic despite their different cultured-terrestrial/freshly-isolated aquatic histories; but there were significant differences in gene content indicative of genomic flux and LGT. Gene content comparisons support previously published in silico predictions for LGT in strain HD100 with substantial conservation of genes predicted to have ancient LGT origins but little conservation of AT-rich genes predicted to be recently acquired.

CONCLUSIONS: The natural niche and dual predatory, and prey-independent growth of the B. bacteriovorus Tiberius strain afforded it extensive non-predatory contact with other marine and freshwater bacteria from which LGT is evident in its genome. Thus despite their arsenal of DNA-lytic enzymes; Bdellovibrio are not always predatory in natural niches and their genomes are shaped by acquiring whole genes from other bacteria.

Electron-impact ionization of the C atom

Time-dependent close-coupling (TDCC), R-matrix-with-pseudostates (RMPS), and time-independent distorted-wave (TIDW) methods are used to calculate electron-impact ionization cross sections for the carbon atom. The TDCC and RMPS results for the 1s22s22p2 ground configuration are in reasonable agreement with the available experimental measurements, while the TIDW results are 30% higher. Ionization of the 1s22s2p3 excited configuration is performed using the TDCC, RMPS, and TIDW methods. Ionization of the 1s22s22p3l (l=0–2) excited configurations is performed using the TDCC and TIDW methods. The ionization cross sections for the excited configurations are much larger than for the ground state. For example, the peak cross section for the 1s22s22p3p excited configuration is an order of magnitude larger than the peak cross section for the 1s22s22p2 ground configuration. The TDCC results are again found to be substantially lower than the TIDW results. The ionization cross-section results will permit the generation of more accurate, generalized collisional-radiative ionization coefficients needed for modeling moderately dense carbon plasmas.

Spectral characterization of families of split graphs

An upper bound for the sum of the squares of the entries of the principal eigenvector corresponding to a vertex subset inducing a k-regular subgraph is introduced and applied to the determination of an upper bound on the order of such induced subgraphs. Furthermore, for some connected graphs we establish a lower bound for the sum of squares of the entries of the principal eigenvector corresponding to the vertices of an independent set. Moreover, a spectral characterization of families of split graphs, involving its index and the entries of the principal eigenvector corresponding to the vertices of the maximum independent set is given. In particular, the complete split graph case is highlighted.

Modelling HIV/AIDS length of stay in Portugal

Tese apresentada como requisito parcial para obtenção do grau de Doutor em Estatística e Gestão de Informação pelo Instituto Superior de Estatística e Gestão de Informação da Universidade Nova de Lisboa

Certificate of Acceptance and Initiation to Canadian Order Chosen Friends - Thomas Cowan

A certificate of initiation and acceptance to the Canadian Order Chosen Friends, Thomas Cowan. The certificate reads "This certifies that evidence has been received that Thomas Cowan has been accepted and initiated by the Council name below, and has thus become a member of the Canadian Order of Chosen Friends, and entitled to all the rights and privileges of membership and a benefit of not exceeding one thousand dollars from the relief fund of said order, which shall in case of death be paid to Annie Cowan his wife in the manner and subject to the conditions set forth in the laws governing said relief fund and in the application for membership. This certificate to be in force and binding when accepted in writing by the said member, with the acceptance attested by the Councilor and Recorder and the seal of the Subordinate Council affixed, so long as said member shall comply with the requirements of the Constitution, Laws and Regulations now in force or hereafter adopted for the government of the Order: otherwise, and also in the case of granting of a new certificate, to be null and void. In witness whereof, we have hereunto attached our signatures, and affixed the seal of the Grand Council of the Canadian Order of Chosen Friends. Dated the Twenty Seventh day of July, A.D. 1891." The front and back of the certificate are available for viewing.

Characterization of the unfolding of a weak focus and modulus of analytic classification

La thèse présente une description géométrique d’un germe de famille générique déployant un champ de vecteurs réel analytique avec un foyer faible à l’origine et son complexifié : le feuilletage holomorphe singulier associé. On montre que deux germes de telles familles sont orbitalement analytiquement équivalents si et seulement si les germes de familles de difféomorphismes déployant la complexification de leurs fonctions de retour de Poincaré sont conjuguées par une conjugaison analytique réelle. Le “caractère réel” de la famille correspond à sa Z2-équivariance dans R^4, et cela s’exprime comme l’invariance du plan réel sous le flot du système laquelle, à son tour, entraîne que l’expansion asymptotique de la fonction de Poincaré est réelle quand le paramètre est réel. Le pullback du plan réel après éclatement par la projection monoidal standard intersecte le feuilletage en une bande de Möbius réelle. La technique d’éclatement des singularités permet aussi de donner une réponse à la question de la “réalisation” d’un germe de famille déployant un germe de difféomorphisme avec un point fixe de multiplicateur égal à −1 et de codimension un comme application de semi-monodromie d’une famille générique déployant un foyer faible d’ordre un. Afin d’étudier l’espace des orbites de l’application de Poincaré, nous utilisons le point de vue de Glutsyuk, puisque la dynamique est linéarisable auprès des points singuliers : pour les valeurs réels du paramètre, notre démarche, classique, utilise une méthode géométrique, soit un changement de coordonée (coordonée “déroulante”) dans lequel la dynamique devient beaucoup plus simple. Mais le prix à payer est que la géométrie locale du plan complexe ambiante devient une surface de Riemann, sur laquelle deux notions de translation sont définies. Après avoir pris le quotient par le relèvement de la dynamique nous obtenons l’espace des orbites, ce qui s’avère être l’union de trois tores complexes plus les points singuliers (l’espace résultant est non-Hausdorff). Les translations, le caractère réel de l’application de Poincaré et le fait que cette application est un carré relient les différentes composantes du “module de Glutsyuk”. Cette propriété implique donc le fait qu’une seule composante de l’invariant Glutsyuk est indépendante.

Acoustic radiation and scattering from cylindrical bodies and analysis of transducer arrays

New mathematical methods to analytically investigate linear acoustic radiation and scattering from cylindrical bodies and transducer arrays are presented. Three problems of interest involving cylinders in an infinite fluid are studied. In all the three problems, the Helmholtz equation is used to model propagation through the fluid and the beam patterns of arrays of transducers are studied. In the first problem, a method is presented to determine the omni-directional and directional far-field pressures radiated by a cylindrical transducer array in an infinite rigid cylindrical baffle. The solution to the Helmholtz equation and the displacement continuity condition at the interface between the array and the surrounding water are used to determine the pressure. The displacement of the surface of each transducer is in the direction of the normal to the array and is assumed to be uniform. Expressions are derived for the pressure radiated by a sector of the array vibrating in-phase, the entire array vibrating in-phase, and a sector of the array phase-shaded to simulate radiation from a rectangular piston. It is shown that the uniform displacement required for generating a source level of 220 dB ref. μPa @ 1m that is omni directional in the azimuthal plane is in the order of 1 micron for typical arrays. Numerical results are presented to show that there is only a small difference between the on-axis pressures radiated by phased cylindrical arrays and planar arrays. The problem is of interest because cylindrical arrays of projectors are often used to search for underwater objects. In the second problem, the errors, when using data-independent, classical, energy and split beam correlation methods, in finding the direction of arrival (DOA) of a plane acoustic wave, caused by the presence of a solid circular elastic cylindrical stiffener near a linear array of hydrophones, are investigated. Scattering from the effectively infinite cylinder is modeled using the exact axisymmetric equations of motion and the total pressures at the hydrophone locations are computed. The effect of the radius of the cylinder, a, the distance between the cylinder and the array, b, the number of hydrophones in the array, 2H, and the angle of incidence of the wave, α, on the error in finding the DOA are illustrated using numerical results. For an array that is about 30 times the wavelength and for small angles of incidence (α<10), the error in finding the DOA using the energy method is less than that using the split beam correlation method with beam steered to α; and in some cases, the error increases when b increases; and the errors in finding the DOA using the energy method and the split beam correlation method with beam steered to α vary approximately as a7 / 4 . The problem is of interest because elastic stiffeners – in nearly acoustically transparent sonar domes that are used to protect arrays of transducers – scatter waves that are incident on it and cause an error in the estimated direction of arrival of the wave. In the third problem, a high-frequency ray-acoustics method is presented and used to determine the interior pressure field when a plane wave is normally incident on a fluid cylinder embedded in another infinite fluid. The pressure field is determined by using geometrical and physical acoustics. The interior pressure is expressed as the sum of the pressures due to all rays that pass through a point. Numerical results are presented for ka = 20 to 100 where k is the acoustic wavenumber of the exterior fluid and a is the radius of the cylinder. The results are in good agreement with those obtained using field theory. The directional responses, to the plane wave, of sectors of a circular array of uniformly distributed hydrophones in the embedded cylinder are then computed. The sectors are used to simulate linear arrays with uniformly distributed normals by using delays. The directional responses are compared with the output from an array in an infinite homogenous fluid. These outputs are of interest as they are used to determine the direction of arrival of the plane wave. Numerical results are presented for a circular array with 32 hydrophones and 12 hydrophones in each sector. The problem is of interest because arrays of hydrophones are housed inside sonar domes and acoustic plane waves from distant sources are scattered by the dome filled with fresh water and cause deterioration in the performance of the array.

Theoretical investigations of an annular elliptical ring microstrip antenna using Green‘s function technique

Analytical expressions for the Green’s function of an annular elliptical ring microstrip antenna (AERMA) are developed and reported. The modal, radiation and input impedance characteristics of the TM, modes are determined from these expressions. The resonant frequencies of odd modes are greater than that of the even modes for all TMnl modes (n = 1, 2, 3, ...) udke elliptical microstrip structures. The radiation pattern and input imedance curves of TMI2 mode on comparison with available experimental result shows good agreement whch provides an independent validation to this technique. The performance of the AERMA is then investigated as a function of thickness and substrate dielectric permittivity.

Optical amplification and stability of spiroquaterphenyl compounds and blends

In this contribution, we present a systematic investigation on a series of spiroquaterphenyl compounds optimised for solid state lasing in the near ultraviolet (UV). Amplified spontaneous emission (ASE) thresholds in the order of 1 μJ/cm2 are obtained in neat (undiluted) films and blends, with emission peaks at 390 1 nm for unsubstituted and meta-substituted quaterphenyls and 400 4 nm for para-ether substituted quaterphenyls. Mixing with a transparent matrix retains a low threshold, shifts the emission to lower wavelengths and allows a better access to modes having their intensity maximum deeper in the film. Chemical design and blending allow an independent tuning of optical and processing properties such as the glass transition.

First-principles electronic theory of non-collinear magnetic order in transition-metal nanowires

The structural, electronic and magnetic properties of one-dimensional 3d transition-metal (TM) monoatomic chains having linear, zigzag and ladder geometries are investigated in the frame-work of first-principles density-functional theory. The stability of long-range magnetic order along the nanowires is determined by computing the corresponding frozen-magnon dispersion relations as a function of the 'spin-wave' vector q. First, we show that the ground-state magnetic orders of V, Mn and Fe linear chains at the equilibrium interatomic distances are non-collinear (NC) spin-density waves (SDWs) with characteristic equilibrium wave vectors q that depend on the composition and interatomic distance. The electronic and magnetic properties of these novel spin-spiral structures are discussed from a local perspective by analyzing the spin-polarized electronic densities of states, the local magnetic moments and the spin-density distributions for representative values q. Second, we investigate the stability of NC spin arrangements in Fe zigzag chains and ladders. We find that the non-collinear SDWs are remarkably stable in the biatomic chains (square ladder), whereas ferromagnetic order (q =0) dominates in zigzag chains (triangular ladders). The different magnetic structures are interpreted in terms of the corresponding effective exchange interactions J(ij) between the local magnetic moments μ(i) and μ(j) at atoms i and j. The effective couplings are derived by fitting a classical Heisenberg model to the ab initio magnon dispersion relations. In addition they are analyzed in the framework of general magnetic phase diagrams having arbitrary first, second, and third nearest-neighbor (NN) interactions J(ij). The effect of external electric fields (EFs) on the stability of NC magnetic order has been quantified for representative monoatomic free-standing and deposited chains. We find that an external EF, which is applied perpendicular to the chains, favors non-collinear order in V chains, whereas it stabilizes the ferromagnetic (FM) order in Fe chains. Moreover, our calculations reveal a change in the magnetic order of V chains deposited on the Cu(110) surface in the presence of external EFs. In this case the NC spiral order, which was unstable in the absence of EF, becomes the most favorable one when perpendicular fields of the order of 0.1 V/Å are applied. As a final application of the theory we study the magnetic interactions within monoatomic TM chains deposited on graphene sheets. One observes that even weak chain substrate hybridizations can modify the magnetic order. Mn and Fe chains show incommensurable NC spin configurations. Remarkably, V chains show a transition from a spiral magnetic order in the freestanding geometry to FM order when they are deposited on a graphene sheet. Some TM-terminated zigzag graphene-nanoribbons, for example V and Fe terminated nanoribbons, also show NC spin configurations. Finally, the magnetic anisotropy energies (MAEs) of TM chains on graphene are investigated. It is shown that Co and Fe chains exhibit significant MAEs and orbital magnetic moments with in-plane easy magnetization axis. The remarkable changes in the magnetic properties of chains on graphene are correlated to charge transfers from the TMs to NN carbon atoms. Goals and limitations of this study and the resulting perspectives of future investigations are discussed.