Exchange Effects and CIDEP

Väitöskirjassa on tutkittu tilastollisen koesuunnittelun teoriaa. Koesuunnittelua tarvitaan, kun tilastollisiin mittauksiin on käytettävissä vain rajallinen määrä resursseja mutta samalla kuitenkin halutaan luotettavaa tietoa. Tutkimuksen kolmessa ensimmäisessä artikkelissa on kehitetty koesuunnitelmia satunnaiskertoimisille regressiomalleille. Malleja voidaan soveltaa, kun tehdään usealle yksilölle peräkkäisiä mittauksia, esimerkiksi eri aikapisteissä. Väitöskirjan artikkeleissa sovelluskohteena ovat olleet puiden rungot, joista on mitattu läpimittoja eri korkeuksilla. Kutakin yksilöä, tässä tapauksessa puunrunkoa, vastaavat omat regressiomallin kertoimet. Koesuunnitelma käsittää tiedon siitä, miten mittausten määrä jakaantuu eri yksilöiden välillä ja yksilöiden sisäisesti. Tavoitteena on joko arvioida mallin keskimääräiset parametrit mahdollisimman tarkasti tai ennustaa uusia havaintoarvoja. Ensimmäisessä artikkelissa on ennustealue on sama kuin havaintoväli ja toisessa se on havaintovälin ulkopuolella. Kolmannessa artikkelissa on esillä käänteisennusteongelma, kun halutaan arvioida pistettä, jossa vastemuuttuja, esim. puun läpimitta, saavuttaa tietyn tason. Koesuunnitelmia vertaillaan keskenään käyttämällä erilaisia optimaalisuuskriteereitä. Kolmannessa ja neljännessä väitöskirjan artikkelissa tarkastellaan DS-kriteeriä, jota on tutkittu vain vähän tähän mennessä. DS-kriteeri on siinä mielessä yleinen, että koesuunnitelman ollessa DS-optimaalinen se on optimaalinen myös monen perinteisen optimaalisuuskriteerin suhteen. Yleensä DS-optimaalista suunnitelmaa ei ole olemassa, mutta suunnitelmia voidaan parantaa DS-kriteerin suhteen. Tutkimuksessa on rajoituttu yksinkertaisiin polynomimalleihin, joten lisätutkimus on tarpeen DS-kriteerin käytöstä laajemmissa yhteyksissä.The thesis consists of five papers and a summary. It has two main themes in the area of experimental design. Firstly, optimal designs for estimation, prediction and inverse prediction are developed in random coefficient linear regression models. Mainly first-degree models are dealt with. The results can be applied in repeated measurements situations. Secondly, a relatively new design criterion, the distance optimality criterion, is introduced. Its properties are studied and some results in estimation and prediction problems deduced. The criterion can be used to find optimal designs or to improve designs in polynomial regression models. It has interesting relations to traditional D- and E-optimality criteria

Innovation through R&D activities in the European context: Antecedents and consequences

Despite the fact that the determinants and the consequences of R&D activities have been extensively studied in previous research, further efforts to integrate disparate streams of literature might bring new insights into innovation decision-making by firms. In particular, this article studies the simultaneous effects that a set of factors (at both company and environmental levels of analysis) have on R&D activity, which explain firm growth. A two-stage probit least squares (2SPLS) estimation is applied to data from the EU-EFIGE/Bruegel-UniCredit dataset for seven European countries for the years 2007-2009. The main findings show that not all the R&D determinants lead to firm growth. In particular, R&D activities are affected by the employment of a significant number of foreign executives, a higher percentage of employees with fixed-term contracts, appropriate labour regulations and access to employees who have received external training, all of which are positively related to firm growth. Based on these results, policy and practical implications to improve firms’ performances are discussed

ontologyX: a suite of R packages for working with ontological data

Ontologies are widely used constructs for encoding and analyzing biomedical data, but the absence of simple and consistent tools has made exploratory and systematic analysis of such data unnecessarily difficult. Here we present three packages which aim to simplify such procedures. The ontologyIndex package enables arbitrary ontologies to be read into R, supports representation of ontological objects by native R types, and provides a parsimonius set of performant functions for querying ontologies. ontologySimilarity and ontologyPlot extend ontologyIndex with functionality for straightforward visualization and semantic similarity calculations, including statistical routines. $\textbf{AVAILABILITY AND IMPLEMENTATION}$: ontologyIndex, ontologyPlot and ontologySimilarity are all available on the Comprehensive R Archive Network website under https://cran.r-project.org/web/packagesThis work was supported by National Institute for Health Research award RG65966 (D.G. and E.T.) and the Medical Research Council programme grant MC_UP_ 0801/1 (D.G. and S.R.)

Infrared spectroscopy of small-molecule endofullerenes

Hydrogen is one of the few molecules which has been incarcerated in the molecular cage of C$_{60}$ and forms endohedral supramolecular complex H$_2$@C$_{60}$. In this confinement hydrogen acquires new properties. Its translational motion becomes quantized and is correlated with its rotations. We applied infrared spectroscopy to study the dynamics of hydrogen isotopologs H$_2$, D$_2$ and HD incarcerated in C$_{60}$. The translational and rotational modes appear as side bands to the hydrogen vibrational mode in the mid infrared part of the absorption spectrum. Because of the large mass difference of hydrogen and C$_{60}$ and the high symmetry of C$_{60}$ the problem is identical to a problem of a vibrating rotor moving in a three-dimensional spherical potential. The translational motion within the C$_{60}$ cavity breaks the inversion symmetry and induces optical activity of H$_2$. We derive potential, rotational, vibrational and dipole moment parameters from the analysis of the infrared absorption spectra. Our results were used to derive the parameters of a pairwise additive five-dimensional potential energy surface for H$_2$@C$_{60}$. The same parameters were used to predict H$_2$ energies inside C$_{70}$[Xu et al., J. Chem. Phys., {\bf 130}, 224306 (2009)]. We compare the predicted energies and the low temperature infrared absorption spectra of H$_2$@C$_{70}$.Comment: Updated author lis

A Fast Association Test for Identifying Pathogenic Variants Involved in Rare Diseases

We present a rapid and powerful inference procedure for identifying loci associated with rare hereditary disorders using Bayesian model comparison. Under a baseline model, disease risk is fixed across all individuals in a study. Under an association model, disease risk depends on a latent bipartition of rare variants into pathogenic and non-pathogenic variants, the number of pathogenic alleles that each individual carries, and the mode of inheritance. A parameter indicating presence of an association and the parameters representing the pathogenicity of each variant and the mode of inheritance can be inferred in a Bayesian framework. Variant-specific prior information derived from allele frequency databases, consequence prediction algorithms, or genomic datasets can be integrated into the inference. Association models can be fitted to different subsets of variants in a locus and compared using a model selection procedure. This procedure can improve inference if only a particular class of variants confers disease risk and can suggest particular disease etiologies related to that class. We show that our method, called BeviMed, is more powerful and informative than existing rare variant association methods in the context of dominant and recessive disorders. The high computational efficiency of our algorithm makes it feasible to test for associations in the large non-coding fraction of the genome. We have applied BeviMed to whole-genome sequencing data from 6,586 individuals with diverse rare diseases. We show that it can identify multiple loci involved in rare diseases, while correctly inferring the modes of inheritance, the likely pathogenic variants, and the variant classes responsible.This work was supported by NIHR award RG65966 (D.G. and E.T.) and the Medical Research Council program grant MC_UP_0801/1 (D.G. and S.R.)

Dynamic properties and optical phase conjugation of two-photon pumped ultrashort blue stimulated emission in a chromophore solution

The dynamic properties of two-photon pumped blue lasing (~470 nm) in the solution of an organic chromophore [2-acetyl-6-(dimethylamino)naphthalene], excited by ~160-fs laser pulses at ~775 nm, have been studied. Both the forward and backward stimulated emission are enhanced by feedback from the reflection at the two optical windows of the solution filled cuvette. Under current experimental conditions, the lasing wavelengths in the forward and backward directions were almost the same, but both blueshifted compared to the fluorescence peak wavelength of the sample solution. The temporal behavior of the lasing output was recorded by a high-speed streak camera system. The multipulse structure and spectral properties of the output lasing are semiquantitatively explained. In addition, excellent optical phase-conjugation properties of the backward stimulated emission were observed; the aberration influences from an aberrator on the backward lasing beam were automatically removed

The South Asian genome

Genetics of disease Microarrays Variant genotypes Population genetics Sequence alignment AllelesThe genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.Whole genome sequencing to discover genetic variants underlying type-2 diabetes, coronary heart disease and related phenotypes amongst Indian Asians. Imperial College Healthcare NHS Trust cBRC 2011-13 (JS Kooner [PI], JC Chambers)