Pseudoknots in prion protein mRNAs confirmed by comparative sequence analysis and pattern searching

The human prion gene contains five copies of a 24 nt repeat that is highly conserved among species. An analysis of folding free energies of the human prion mRNA, in particular in the repeat region, suggested biased codon selection and the presence of RNA patterns. In particular, pseudoknots, similar to the one predicted by Wills in the human prion mRNA, were identified in the repeat region of all available prion mRNAs available in GenBank, but not those of birds and the red slider turtle. An alignment of these mRNAs, which share low sequence homology, shows several co-variations that maintain the pseudoknot pattern. The presence of pseudoknots in yeast Sup35p and Rnq1 suggests acquisition in the prokaryotic era. Computer generated three-dimensional structures of the human prion pseudoknot highlight protein and RNA interaction domains, which suggest a possible effect in prion protein translation. The role of pseudoknots in prion diseases is discussed as individuals with extra copies of the 24 nt repeat develop the familial form of Creutzfeldt–Jakob disease.

Characterization of a Low-Molecular-Weight Glutenin Subunit Gene from Bread Wheat and the Corresponding Protein That Represents a Major Subunit of the Glutenin Polymer1

Both high- and low-molecular-weight glutenin subunits (LMW-GS) play the major role in determining the viscoelastic properties of wheat (Triticum aestivum L.) flour. To date there has been no clear correspondence between the amino acid sequences of LMW-GS derived from DNA sequencing and those of actual LMW-GS present in the endosperm. We have characterized a particular LMW-GS from hexaploid bread wheat, a major component of the glutenin polymer, which we call the 42K LMW-GS, and have isolated and sequenced the putative corresponding gene. Extensive amino acid sequences obtained directly for this 42K LMW-GS indicate correspondence between this protein and the putative corresponding gene. This subunit did not show a cysteine (Cys) at position 5, in contrast to what has frequently been reported for nucleotide-based sequences of LMW-GS. This Cys has been replaced by one occurring in the repeated-sequence domain, leaving the total number of Cys residues in the molecule the same as in various other LMW-GS. On the basis of the deduced amino acid sequence and literature-based assignment of disulfide linkages, a computer-generated molecular model of the 42K subunit was constructed.

Three-dimensional tracking of motile bacteria near a solid planar surface.

Knowing how motile bacteria move near and along a solid surface is crucial to understanding such diverse phenomena as the migration of infectious bacteria along a catheter, biofilm growth, and the movement of bacteria through the pore spaces of saturated soil, a critical step in the in situ bioremediation of contaminated aquifers. In this study, a tracking microscope is used to record the three-dimensional motion of Escherichia coli near a planar glass surface. Data from the tracking microscope are analyzed to quantify the effects of bacteria-surface interactions on the swimming behavior of bacteria. The speed of cells approaching the surface is found to decrease in agreement with the mathematical model of Ramia et al. [Ramia, M., Tullock, D. L. & Phan-Tien, N. (1993) Biophys J. 65,755-778], which represents the bacteria as spheres with a single polar flagellum rotating at a constant rate. The tendency of cells to swim adjacent to the surface is shown in computer-generated reproductions of cell traces. The attractive interaction potential between the cells and the solid surface is offered as one of several possible explanations for this tendency.

Breadth-first search and the Andrews-Curtis conjecture

Andrews and Curtis conjectured in 1965 that every balanced presentation of the trivial group can be transformed into a standard presentation by a finite sequence of elementary transformations. Recent computational work by Miasnikov and Myasnikov on this problem has been based on genetic algorithms. We show that a computational attack based on a breadth-first search of the tree of equivalent presentations is also viable, and seems to outperform that based on genetic algorithms. It allows us to extract shorter proofs (in some cases, provably shortest) and to consider the length thirteen case for two generators. We prove that, up to equivalence, there is a unique minimum potential counterexample.

Cost models for engineering services

This thesis describes the procedure and results from four years research undertaken through the IHD (Interdisciplinary Higher Degrees) Scheme at Aston University in Birmingham, sponsored by the SERC (Science and Engineering Research Council) and Monk Dunstone Associates, Chartered Quantity Surveyors. A stochastic networking technique VERT (Venture Evaluation and Review Technique) was used to model the pre-tender costs of public health, heating ventilating, air-conditioning, fire protection, lifts and electrical installations within office developments. The model enabled the quantity surveyor to analyse, manipulate and explore complex scenarios which previously had defied ready mathematical analysis. The process involved the examination of historical material costs, labour factors and design performance data. Components and installation types were defined and formatted. Data was updated and adjusted using mechanical and electrical pre-tender cost indices and location, selection of contractor, contract sum, height and site condition factors. Ranges of cost, time and performance data were represented by probability density functions and defined by constant, uniform, normal and beta distributions. These variables and a network of the interrelationships between services components provided the framework for analysis. The VERT program, in this particular study, relied upon Monte Carlo simulation to model the uncertainties associated with pre-tender estimates of all possible installations. The computer generated output in the form of relative and cumulative frequency distributions of current element and total services costs, critical path analyses and details of statistical parameters. From this data alternative design solutions were compared, the degree of risk associated with estimates was determined, heuristics were tested and redeveloped, and cost significant items were isolated for closer examination. The resultant models successfully combined cost, time and performance factors and provided the quantity surveyor with an appreciation of the cost ranges associated with the various engineering services design options.

The computerisation of community pharmacy

Computers have, over the past 10 to 15 years, become an integral part of many activities carried out by British community pharmacists. This thesis employs quantitative and qualitative research methods to explore the use of computers and other forms of information technology (IT) in a number of these activities. Mail questionnaires were used to estimate the level of IT use among British community pharmacists in 1989 and 1990. Comparison of the results suggests that the percentage of community pharmacists using computers and other forms of IT is increasing, and that the range of applications to which pharmacy computers are put is expanding. The use of an electronic, on-line information service, PINS, by community pharmacists was investigated using mail questionnaires. The majority of community pharmacists who subscribed to the service, and who responded to the questionnaire, claimed to use PINS less than they had expected to. In addition, most did not find it user-friendly. A computer program to aid pharmacists when responding to their patients' symptoms was investigated using interviews and direct observation. The aid was not found to help pharmacists in responding to patients' symptoms because of impracticalities involved in its operation. Use of the same computer program by members of the public without the involvement of a pharmacist was also studied. In this setting, the program was favourably accepted by the majority of those who used it. Provision of computer generated information leaflets from pharmacies was investigated using mail questionnaires and interviews. The leaflets were found to be popular with the majority of recipients interviewed. Since starting to give out the leaflets, 27 out of 55 pharmacists who responded to the questionnaire had experienced an increase in the numbers of prescriptions they dispensed. 46 had experienced an increase in the number of patient enquiries they received.

Multispectral retinal image analysis:a novel non-invasive tool for retinal imaging

Purpose-To develop a non-invasive method for quantification of blood and pigment distributions across the posterior pole of the fundus from multispectral images using a computer-generated reflectance model of the fundus. Methods - A computer model was developed to simulate light interaction with the fundus at different wavelengths. The distribution of macular pigment (MP) and retinal haemoglobins in the fundus was obtained by comparing the model predictions with multispectral image data at each pixel. Fundus images were acquired from 16 healthy subjects from various ethnic backgrounds and parametric maps showing the distribution of MP and of retinal haemoglobins throughout the posterior pole were computed. Results - The relative distributions of MP and retinal haemoglobins in the subjects were successfully derived from multispectral images acquired at wavelengths 507, 525, 552, 585, 596, and 611?nm, providing certain conditions were met and eye movement between exposures was minimal. Recovery of other fundus pigments was not feasible and further development of the imaging technique and refinement of the software are necessary to understand the full potential of multispectral retinal image analysis. Conclusion - The distributions of MP and retinal haemoglobins obtained in this preliminary investigation are in good agreement with published data on normal subjects. The ongoing development of the imaging system should allow for absolute parameter values to be computed. A further study will investigate subjects with known pathologies to determine the effectiveness of the method as a screening and diagnostic tool.

BMI not WHR modulates BOLD fMRI responses in a sub-cortical reward network when participants judge the attractiveness of human female bodies

In perceptual terms, the human body is a complex 3d shape which has to be interpreted by the observer to judge its attractiveness. Both body mass and shape have been suggested as strong predictors of female attractiveness. Normally body mass and shape co-vary, and it is difficult to differentiate their separate effects. A recent study suggested that altering body mass does not modulate activity in the reward mechanisms of the brain, but shape does. However, using computer generated female body-shaped greyscale images, based on a Principal Component Analysis of female bodies, we were able to construct images which covary with real female body mass (indexed with BMI) and not with body shape (indexed with WHR), and vice versa. Twelve observers (6 male and 6 female) rated these images for attractiveness during an fMRI study. The attractiveness ratings were correlated with changes in BMI and not WHR. Our primary fMRI results demonstrated that in addition to activation in higher visual areas (such as the extrastriate body area), changing BMI also modulated activity in the caudate nucleus, and other parts of the brain reward system. This shows that BMI, not WHR, modulates reward mechanisms in the brain and we infer that this may have important implications for judgements of ideal body size in eating disordered individuals.

The mosaic test:measuring the effectiveness of colour-based image retrieval

A variety of content-based image retrieval systems exist which enable users to perform image retrieval based on colour content - i.e., colour-based image retrieval. For the production of media for use in television and film, colour-based image retrieval is useful for retrieving specifically coloured animations, graphics or videos from large databases (by comparing user queries to the colour content of extracted key frames). It is also useful to graphic artists creating realistic computer-generated imagery (CGI). Unfortunately, current methods for evaluating colour-based image retrieval systems have 2 major drawbacks. Firstly, the relevance of images retrieved during the task cannot be measured reliably. Secondly, existing methods do not account for the creative design activity known as reflection-in-action. Consequently, the development and application of novel and potentially more effective colour-based image retrieval approaches, better supporting the large number of users creating media for use in television and film productions, is not possible as their efficacy cannot be reliably measured and compared to existing technologies. As a solution to the problem, this paper introduces the Mosaic Test. The Mosaic Test is a user-based evaluation approach in which participants complete an image mosaic of a predetermined target image, using the colour-based image retrieval system that is being evaluated. In this paper, we introduce the Mosaic Test and report on a user evaluation. The findings of the study reveal that the Mosaic Test overcomes the 2 major drawbacks associated with existing evaluation methods and does not require expert participants. © 2012 Springer Science+Business Media, LLC.

Effectiveness of peer counseling on high school students who failed two or more classes in a nine week quarter

The purpose of this study was to examine the effectiveness of peer counseling on high school students who have previously failed two or more classes in a nine week quarter.^ This study was constructed by comparing students who previously failed and were subsequently given peer counseling with a matched group of students who failed and did not receive peer counseling.^ To test the proposed research question, 324 students from a large urban school system were randomly chosen from a computer generated list of students who failed courses, matched on variables of number of classes failed, grade level and gender. One student from each matched pair was randomly placed in either the experimental or control group. 162 students from Group 1 (experimental) were assigned a peer counselor with their pair assigned to Group 2 (control). Group 1 received peer counseling at least 4 times during the third nine week academic quarter (Quarter 3) while Group 2 did not.^ The Grade Point Averages (GPA) for all students were collected both at the end of Quarter 2 and Quarter 3, at which time peer counseling was terminated. GPA's were also collected nine weeks after counseling was terminated.^ Results were determined by multiple regression, analysis of covariance and t-test. A level of significance was set at.05. There was significant increase in the GPA's of those counseled students immediately after peer counseling and also nine weeks after counseling was terminated, while the group not receiving peer counseling showed no increase. It was noted that there were significantly more school drop-outs from the non-counseled group than the counseled group. The number of classes failed, high school attended, grade level and gender were not found to be significant.^ The conclusion from this study was that peer counseling does impact significantly on the GPA's of students experiencing academic failure. Recommendations from this study were to implement and expand peer counseling programs with more failing students, continue counseling for longer than one quarter, include students in drop-out programs and students from different socio-economic and racial backgrounds, and conduct subsequent evaluation. ^

Group presence in virtual worlds: Supporting collaborative e-learning

Even though e-learning endeavors have significantly proliferated in recent years, current e-learning technologies provide poor support for group-oriented learning. The now popular virtual world's technologies offer a possible solution. Virtual worlds provide the users with a 3D - computer generated shared space in which they can meet and interact through their virtual representations. Virtual worlds are very successful in developing high levels of engagement, presence and group presence in the users. These elements are also desired in educational settings since they are expected to enhance performance. The goal of this research is to test the hypothesis that a virtual world learning environment provides better support for group-oriented collaborative e-learning than other learning environments, because it facilitates the emergence of group presence. To achieve this, a quasi-experimental study was conducted and data was gathered through the use of various survey instruments and a set of collaborative tasks assigned to the participants. Data was gathered on the dependent variables: Engagement, Group Presence, Individual Presence, Perceived Individual Presence, Perceived Group Presence and Performance. The data was analyzed using the statistical procedures of Factor Analysis, Path Analysis, Analysis of Variance (ANOVA) and Multivariate Analysis of Variance (MANOVA). The study provides support for the hypothesis. The results also show that virtual world learning environments are better than other learning environments in supporting the development of all the dependent variables. It also shows that while only Individual Presence has a significant direct effect on Performance; it is highly correlated with both Engagement and Group Presence. This suggests that these are also important in regards to performance. Developers of e-learning endeavors and educators should incorporate virtual world technologies in their efforts in order to take advantage of the benefit they provide for e-learning group collaboration.

FIU in 2020

Computer-generated video that presents a vision for Florida International University's appearance in the year 2020.

An augmented reality pipeline to create scenes with coherent illumination using textured cuboids

Shadows and illumination play an important role when generating a realistic scene in computer graphics. Most of the Augmented Reality (AR) systems track markers placed in a real scene and retrieve their position and orientation to serve as a frame of reference for added computer generated content, thereby producing an augmented scene. Realistic depiction of augmented content with coherent visual cues is a desired goal in many AR applications. However, rendering an augmented scene with realistic illumination is a complex task. Many existent approaches rely on a non automated pre-processing phase to retrieve illumination parameters from the scene. Other techniques rely on specific markers that contain light probes to perform environment lighting estimation. This study aims at designing a method to create AR applications with coherent illumination and shadows, using a textured cuboid marker, that does not require a training phase to provide lighting information. Such marker may be easily found in common environments: most of product packaging satisfies such characteristics. Thus, we propose a way to estimate a directional light configuration using multiple texture tracking to render AR scenes in a realistic fashion. We also propose a novel feature descriptor that is used to perform multiple texture tracking. Our descriptor is an extension of the binary descriptor, named discrete descriptor, and outperforms current state-of-the-art methods in speed, while maintaining their accuracy.

Identity Change Impacts Autobiographical Reconstruction of Identity-Relevant Events: Influences of the Self-System on Remembering

The focus on how one is behaving, feeling, and thinking, provides a powerful source of self-knowledge. How is this self-knowledge utilized in the dynamic reconstruction of autobiographical memories? How, in turn, might autobiographical memories support identity and the self-system? I address these questions through a critical review of the literature on autobiographical memory and the self-system, with a special focus on the self-concept, self-knowledge, and identity. I then outline the methods and results of a prospective longitudinal study examining the effects of an identity change on memory for events related to that identity. Participant-rated memory characteristics, computer-generated ratings of narrative content and structure, and neutral-observer ratings of coherence were examined for changes over time related to an identity-change, as well as for their ability to predict an identity-change. The conclusions from this study are threefold: (1) when the rated centrality of an event decreases, the reported instances of retrieval, as well as the phenomenology associated with retrieval and the number of words used to describe the memory, also decrease; (2) memory accuracy (here, estimating past behaviors) was not influenced by an identity change; and (3) remembering is not unidirectional – characteristics of identity-relevant memories and the life story predict and may help support persistence with an identity (here, an academic trajectory).

Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial

BACKGROUND: Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment. We present a pre-planned analysis of the efficacy and side-effects of a randomised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up.

METHODS: CHHiP is a randomised, phase 3, non-inferiority trial that recruited men with localised prostate cancer (pT1b-T3aN0M0). Patients were randomly assigned (1:1:1) to conventional (74 Gy delivered in 37 fractions over 7·4 weeks) or one of two hypofractionated schedules (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks) all delivered with intensity-modulated techniques. Most patients were given radiotherapy with 3-6 months of neoadjuvant and concurrent androgen suppression. Randomisation was by computer-generated random permuted blocks, stratified by National Comprehensive Cancer Network (NCCN) risk group and radiotherapy treatment centre, and treatment allocation was not masked. The primary endpoint was time to biochemical or clinical failure; the critical hazard ratio (HR) for non-inferiority was 1·208. Analysis was by intention to treat. Long-term follow-up continues. The CHHiP trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN97182923.

FINDINGS: Between Oct 18, 2002, and June 17, 2011, 3216 men were enrolled from 71 centres and randomly assigned (74 Gy group, 1065 patients; 60 Gy group, 1074 patients; 57 Gy group, 1077 patients). Median follow-up was 62·4 months (IQR 53·9-77·0). The proportion of patients who were biochemical or clinical failure free at 5 years was 88·3% (95% CI 86·0-90·2) in the 74 Gy group, 90·6% (88·5-92·3) in the 60 Gy group, and 85·9% (83·4-88·0) in the 57 Gy group. 60 Gy was non-inferior to 74 Gy (HR 0·84 [90% CI 0·68-1·03], pNI=0·0018) but non-inferiority could not be claimed for 57 Gy compared with 74 Gy (HR 1·20 [0·99-1·46], pNI=0·48). Long-term side-effects were similar in the hypofractionated groups compared with the conventional group. There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures. The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group (RTOG) grade 2 or worse bowel and bladder adverse events was 13·7% (111 events) and 9·1% (66 events) in the 74 Gy group, 11·9% (105 events) and 11·7% (88 events) in the 60 Gy group, 11·3% (95 events) and 6·6% (57 events) in the 57 Gy group, respectively. No treatment-related deaths were reported.

INTERPRETATION: Hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions and is recommended as a new standard of care for external-beam radiotherapy of localised prostate cancer.

FUNDING: Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.