LATENT VARIABLE GENERALIZED LINEAR MODELS

Generalized Linear Models (GLMs) (McCullagh and Nelder, 1989) provide a unified framework for fixed effect models where response data arise from exponential family distributions. Much recent research has attempted to extend the framework to include random effects in the linear predictors. Different methodologies have been employed to solve different motivating problems, for example Generalized Linear Mixed Models (Clayton, 1994) and Multilevel Models (Goldstein, 1995). A thorough review and classification of this and related material is presented. In Item Response Theory (IRT) subjects are tested using banks of pre-calibrated test items. A useful model is based on the logistic function with a binary response dependent on the unknown ability of the subject. Item parameters contribute to the probability of a correct response. Within the framework of the GLM, a latent variable, the unknown ability, is introduced as a new component of the linear predictor. This approach affords the opportunity to structure intercept and slope parameters so that item characteristics are represented. A methodology for fitting such GLMs with latent variables, based on the EM algorithm (Dempster, Laird and Rubin, 1977) and using standard Generalized Linear Model fitting software GLIM (Payne, 1987) to perform the expectation step, is developed and applied to a model for binary response data. Accurate numerical integration to evaluate the likelihood functions is a vital part of the computational process. A study of the comparative benefits of two different integration strategies is undertaken and leads to the adoption, unusually, of Gauss-Legendre rules. It is shown how the fitting algorithms are implemented with GLIM programs which incorporate FORTRAN subroutines. Examples from IRT are given. A simulation study is undertaken to investigate the sampling distributions of the estimators and the effect of certain numerical attributes of the computational process. Finally a generalized latent variable model is developed for responses from any exponential family distribution

An investigation of the romantic ballet in its sociocultural context in Paris and London, 1830 to 1850

Historians have made a considerable contribution to the study of the Romantic ballet in terms of chronological development, the Romantic movement in the arts and the contribution of specific dancers and choreographers; very little research has been attempted to date on the interrelationship between the dance form and the wide range of human experience of the period. This holistic approach provides insight into form, content and stagecraft; political, economic and social influences; the prevailing artistic aesthetic and cultural climate; sex, gender and class issues; and the priorities, value system and nuances of the times. Recent work by historians and social scientists (eg Brinson 1981, Adshead 1983, Spencer 1985, Hanna 1988, Garafola 1989) advocates a recognition of the role of social and cultural systems in the evaluation of dance. This approach further ackowledges the equal status of all cultures, and has opened up areas of African performing dance in cultural systems outside the west. My parallel investigation of the gumboot dance in its South African context, which appears in Appendix B, provides an example. The first half of the nineteenth century was characterized by the disruptive beginnings of the emergent industrial world, centred in Paris and London; and the Romantic ballet tradition reached its greatest heights at this time. Chapter one establishes the political, economic, social and artistic environment, and identifies middle class dominance as a key factor. Chapters two and three focus primarily on the three great ballets of the age, La Sylphide, 1832, Giselie, 1841, and Pas de Quatre, 1845, as expressions of the essential duality of the times, and of Romantic synaesthesia in the arts, which enabled them to transcend the pedestrian bourgeois materialism of faciliatators and audience. Chapter four examines the images of the idealized ballerina and the 'Victorian' middle class woman in relation to bourgeois male attitudes to female sexuality, gender and class. The conclusion sums up the themes of duality, middle class influence, and the Romantic aesthetic, and discusses the prevalent notion that this period was identified as a 'golden age' of the Romantic ballet

The needs of informal grandparent caregivers and how they are met at the Kinship Family Center

Seventeen grandparent caregivers, who have primary responsibility for one or more grandchildren and do not have a parent of the grandchildren living in the household, were interviewed to evaluate the effectiveness of the services offered by Kinship Family Center (KFC), a non-profit support agency for relative caregivers and the children in their care. Kinship Family Center is a program of the Central City Lutheran Mission and is funded by the San Bernardino County Department of Children\u27s Services. The researchers found that KFC was an effective asset for informal grandparent caregivers. For grandparents, it was a source of support and comfort in their role of second time around parents. For children, it served as a means to help identify with other children in similar situations

Operator Sequence Alters Gene Expression Independently of Transcription Factor Occupancy in Bacteria

A canonical quantitative view of transcriptional regulation holds that the only role of operator sequence is to set the probability of transcription factor binding, with operator occupancy determining the level of gene expression. In this work, we test this idea by characterizing repression in vivo and the binding of RNA polymerase in vitro in experiments where operators of various sequences were placed either upstream or downstream from the promoter in Escherichia coli. Surprisingly, we find that operators with a weaker binding affinity can yield higher repression levels than stronger operators. Repressor bound to upstream operators modulates promoter escape, and the magnitude of this modulation is not correlated with the repressor-operator binding affinity. This suggests that operator sequences may modulate transcription by altering the nature of the interaction of the bound transcription factor with the transcriptional machinery, implying a new layer of sequence dependence that must be confronted in the quantitative understanding of gene expression

Role of complement genetic variants in inflammatory diseases by an interactive database and protein structure modelling

The rare diseases atypical haemolytic uraemic syndrome (aHUS) and C3 glomerulopathy (C3G) are associated with dysregulation of complement activation. It is unclear which genes most frequently predispose to aHUS or C3G. Accordingly, a six- centre analysis of 610 rare genetic variants in 13 mostly complement genes from >3500 patients with aHUS and C3G was performed. A new interactive Database of Complement Gene Variants was developed to extract allele frequencies for these 13 genes using the Exome Aggregation Consortium server as the reference genome. For aHUS, significantly more protein-altering rare variation was found in the five genes CFH, CFI, CD46, C3 and DGKE than in ExAC. For C3G, an association was only found for rare variants in C3 and the N-terminal C3b-binding or C-terminal non-surface-associated regions of factor H (FH). FH is the major regulator of C3b and its Tyr402His polymorphism is an age-related macular degeneration risk-factor. To better understand FH complement binding, the solution structures of both allotypes were studied. Starting from known FH short complement regulator domains and glycan structures, small angle X-ray scattering data were fitted using Monte Carlo methods to determine atomistic structures for monomeric FH. The analysis of 29,715 physically realistic but randomised FH conformations resulted in 100 similar best-fit FH structures for each allotype. Two distinct molecular structures resulted; an extended N-terminal domain arrangement with a folded-back C-terminus, or an extended C-terminus and folded-back N-terminus. To clarify FH functional roles in host protection, crystal structures for the FH complexes with C3b and C3dg revealed that the extended N-terminal conformation accounted for C3b fluid phase regulation, the extended C-terminal conformation accounted for C3d binding, and both conformations accounted for bivalent FH binding to the host cell-surface. Finally, statistical analyses indicated that the structural location of rare variants in complement may predict the occurrences of aHUS or C3G

Interactions of Bunyamwera Virus Nucleocapsid Protein and Encapsidation of Viral RNA

This project concerns the identification and characterisation of some of the molecular interactions of the Bunyamwera virus (BUN) nucleocapsid (N) protein, and attempts to construct a model for encapsidation of viral RNA by N. BUN is the prototype virus of the Bunyaviridae, a family of negative-strand viruses with tripartite genomes. All BUN genome and antigenome RNAs are encapsidated by N. This interaction was investigated in vitro by expressing His-tagged BUN N in bacteria, purifying it in its native form and developing binding assays to analyse its association with a short radiolabelled riboprobe consisting of the termini of the BUNS segment. N was demonstrated to bind the riboprobe by Northwestern, gel electrophoretic mobility shift (GEMSA) and filter-binding assays. The complexes were found to possess a similar level of resistance to digestion with ribonuclease as authentic nucleocapsids. Analysis by GEMSA was interpreted to indicate complete encapsidation of the riboprobe by N, with a number of discrete complexes presumed to be intermediates in the sequential encapsidation process apparent. Filter-binding assays were utilised to determine the binding kinetics. The resultant dissociation constant was similar to dissociation constants obtained for other negative-strand virus N-RNA interactions and implied that binding was strong. Supporting the latter observation was the ability of complexes to form over a wide range of ionic conditions. The binding kinetics also indicated that the binding of N to the riboprobe was co-operative, reinforced by the demonstration that the capacity of N to bind RNA was dependent on its concentration. The 5' terminus of each segment RNA had been implicated in encapsidation initiation, but no direct evidence had been produced. To investigate the presence of an encapsidation signal, competitive binding assays were set up with various RNA species. The 5' 32 terminal nucleotides of the BUN S segment were bound selectively, implicating this region in encapsidation initiation. In addition, N was capable of binding any RNA non-selectively and to a low degree, indicating the presence of two modes of binding. Predictions of the secondary structure of 5' terminal sequences revealed potential stem-loops containing a consensus sequence in the loop region that had previously been found to be essential for transcription of a recombinant BUN S segment in a minireplicon system. The stem-loop was suggested to constitute an encapsidation signal, supported by the inability of an RNA containing the same sequence but not predicted to form the stem-loop to be bound selectively. BUN mRNA is not normally encapsidated and possesses a capped, heterogeneous primer sequence on its 5' end. The predictions of secondary structure were extended to propose a mechanism of inhibition of encapsidation by the primer sequence, which, under certain circumstances, was suggested to be reversible when required. The information obtained on N-RNA interactions was used to propose a model for encapsidation in BUN. The co-operative nature of N-RNA binding suggested that multimerisation of N took place. This was investigated by expressing N as fusion proteins in the mammalian two- hybrid system, and a potential self-association was identified. This was supported by the co-immunoprecipitation of native N with His-tagged N in mammalian cells. However, neither the amino nor the carboxy half of N was found to be capable of interacting with His-tagged N exclusively. No evidence of an interaction between the viral polymerase, L, and N or between L and the non-structural viral protein NSs was obtained using the mammalian two-hybrid system, and NSs was not found to multimerise. However, a weak interaction between N and NSs was identified. The potential role of this interaction in the mechanisms of transcription inhibition or interferon antagonism ascribed to NSs is discussed

Exploring the genetic and mechanistic basis of resistance to take-all disease in wheat

Take-all, caused by the soil-borne ascomycete fungus Gaeumannomyces graminis var. tritici, (Ggt), is a root disease that devastates wheat production worldwide. Current control measures consist of partially effective chemical seed dressings and cultural methods such as crop rotation. There is currently no genetic control of the disease. The first aim of this PhD project was to characterise a range of diploid and hexaploid wheat germplasm that possess a promising level of take-all resistance under field conditions. Both above and below ground phenotyping was carried out and soil moisture probes were used to evaluate upper root function for a range of hexaploid varieties. A diploid Triticum monococcum MDR037 (S) X MDR046 (R) mapping population was screened and revealed a good spread in susceptibility to take-all across two field seasons. The population has subsequently been genotyped and genetic analyses will be carried out to explore the genetic basis of resistance. Phialophora fungal species, belonging to the genus Gaeumannomyces, colonise wheat roots but do not destroy the vascular tissue and have previously been found to suppress take-all disease. In the second approach to control Ggt, winter wheat varieties on the AHDB Recommended List (RL) were screened for their ability to build-up natural populations of Phialophora fungi in the field. Differences were revealed in their potential to build-up Phialophora spp. under a first wheat crop. A Phialophora isolate collection was gathered and draft genomes were sequenced, assembled and annotated for the three Phialophora spp. found in UK soils. Preliminary analysis suggests that considerable polymorphism may exist between homologous genes found in all three species. These findings provide a novel contribution to the potential of these two differing control mechanisms against take-all disease

Improving Requirements Tracing via Information Retrieval

Abstrac

The Ursinus Weekly, April 27, 1953

Y to sponsor panel meeting with Albright • Price, Merrifield, Haines, Hartman to head WSGA, WAA, YWCA, YMCA • May Day dancers prepare pageant for gala weekend • Concert presented by Meistersingers • Fraternities plan May dinner dances • Sororities make plans for shore visits, dinner dances • Group plays to be given • Eight win full scholarships • French teachers\u27 conference held at Ursinus, April 25 • Thespians to give Two blind mice • Friedlin crowned queen; Cub & Key honors five • Radomski, Wong elected to pre-med society offices • Class and council petitioning ends Friday • Jones reads from works of Noyes and Lindsay on Tuesday • Editorials: Tradition vs. common sense • I love Spring! • Helfferich named to board • Career offer for grads • Letters to the editor • Are you wasting money? • Alumni news • U.C. co-ed gives inside scoop on life in a boys\u27 dormitory • Ursinus professors are authorities in subject fields • From memoirs of a freshman: A visit to the Supply Store • Bears drop track meet to West Chester, 69-57 • Bryn Mawr tops girls in tennis • Baseball team loses, 8-7; But tops Graterford, 7-3 • East Stroudsburg routs Belles, 5-0 • Men\u27s tennis team loses, 5-4 • Belles, Albright vie in softball opener • Court squad downs Chestnut Hill, 5-0 • Hutch twirls shut-out; Bears beat Pharmacy, 20-0https://digitalcommons.ursinus.edu/weekly/1518/thumbnail.jp