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E Garner

Publications and source records attributed to E Garner.

17 recordsLinked to original sources
PubMed2000

Radial transformation-associated recombination cloning from the mouse genome: isolation of Tg.AC transgene with flanking DNAs.

Transformation-associated recombination (TAR) cloning allows entire genes and large chromosomal regions to be specifically, accurately, and quickly isolated from total genomic DNA. We report the first example of radial TAR cloning from the mouse genome. Tg.AC mice carry a zeta-globin promoter/v-Ha-ras transgene. Fluorescence in situ hybridization localized the transgene integrant as a single site proximal to the centromere of chromosome 11. Radial TAR cloning in yeast was utilized to create orientation-specific yeast artificial chromosomes (YACs) to explore the possibility that cis-flanking regions were involved in transgene expression. YACs containing variable lengths of 5' or 3' flanking chromosome 11 DNA and the Tg.AC transgene were specifically chosen, converted to bacterial artificial chromosomes (BACs), and assayed for their ability to promote transcription of the transgene following transfection into an FVB/N carcinoma cell line. A transgene-specific reverse transcription-polymerase chain reaction assay was utilized to examine RNA transcripts from stably transfected clones. All Tg.AC BACs expressed the transgene in this in vitro system. This report describes the cloning of the v-Ha-ras transgene and suggests that transcriptional activity may not require cis elements flanking the transgene's integration site.

Animals↗
PubMed2000

Viscoelastic dissipation in compact bone: implications for stress-induced fluid flow in bone.

Viscoelastic properties of wet and dry human compact bone were studied in torsion and in bending for both the longitudinal and transverse directions at frequencies from 5 mHz to 5 kHz in bending to more than 50 kHz in torsion. Two series of tests were done for different longitudinal and transverse specimens from a human tibia. Wet bone exhibited a larger viscoelastic damping tan delta (phase between stress and strain sinusoids) than dry bone over a broad range of frequency. All the results had in common a relative minimum in tan delta over a frequency range, 1 to 100 Hz, which is predominantly contained in normal activities. This behavior is inconsistent with an optimal "design" for bone as a shock absorber. There was no definitive damping peak in the range of frequencies explored, which could be attributed to fluid flow in the porosity of bone.

Aged↗
PubMed1999

Predicting Binding Regions within Disordered Proteins.

Disordered regions are sequences within proteins that fail to fold into a fixed tertiary structure and have been shown to be involved in a variety of biological functions. We recently applied neural network predictors of disorder developed from X-ray data to several protein sequences characterized as disordered by NMR (Garner, Cannon, Romero, Obradovic and Dunker, Genome Informatics, 9:201-213, 1998). A few predictions on the NMR-characterized disordered regions were noted to contain false negative indications of order that correlated with regions of function. These and additional examples are examined in more detail here. Overall, 8 of 9 functional segments in 5 disordered proteins were identified or partially identified by this approach. The functions of these regions appear to involve binding to DNA, RNA, and proteins. These regions are known to undergo disorder-to-order transitions upon binding. This apparent ability of the predictors to identify functional regions in disordered proteins could be due to the existence of different flavors, or sub-classes of disorder, originating from the sequence of the disordered regions and perhaps owing to local inclinations toward order. These different flavors may be a characteristic that could be used to identify binding regions within proteins that are difficult to characterize structurally.

Journal Article↗
PubMed1998

Designing an evaluation for a multiple-strategy community intervention: the North Coast Stay on Your Feet program.

Evaluation of the North Coast Stay on Your Feet falls prevention program is described as a case study of a comprehensive evaluation design for multi-strategic community interventions. Qualitative and quantitative methods were used to evaluate the program at formative, process and outcome levels. Formative evaluation used literature review, focus groups, mail-out and telephone survey methods to gather evidence from publications, older people, health workers, local business, media and government bodies. It included an analysis of demographic and hospital databases and identified incidence, causal pathways, knowledge, attitudes, behaviour, consequences and effectiveness of potential strategies. Process evaluation employed auditing, monitoring and telephone surveys to maintain an inventory of intervention activities and to track the reach of the program. Outcome evaluation involved a longitudinal study of intervention and control cohorts, surveyed before, during and after the intervention by telephone to monitor changes in knowledge, attitudes, risk and falls incidence. The survey instrument was designed for both formative and outcome evaluation, and analysis reflected the research design by incorporating repeat measures and adjusting for bias and confounding. Outcome validity was cross-checked via hospital admission rates. A novel, integrated framework for presenting inputs, activities and outcomes from all stages of the program is described. This framework facilitated feedback to stakeholders and enabled subsequent rapid adjustment of the intervention. Rigorous evaluation combined with clear presentation of findings helped to engender intersectoral support and obtain funding grants for extended implementation and evaluation. It also helped Stay on Your Feet to become a model for other falls prevention programs within Australia and internationally.

Accidental Falls↗
PubMed1998

The Sequence Attribute Method for Determining Relationships Between Sequence and Protein Disorder.

The conditional probability, P(s|x), is a statement of the probability that the event, s, will occur given prior knowledge for the value of x. If x is given and if s is randomly distributed, then an empirical approximation of the true conditional probability can be computed by the application of Bayes' Theorem. Here s represents one of two structural classes, either ordered, s (o), or disordered, s (d), and x represents an attribute value calculated over a window of 21 amino acids. Plots of P(s|x) versus x provide information about the correlation between the given sequence attribute and disorder or order. These conditional probability plots allow quantitative comparisons between individual attributes for their ability to discriminate between order and disorder states. Using such quantitative comparisons, 38 different sequence attributes have been rank-ordered. Attributes based on cysteine, the aromatics, flexible tendencies, and charge were found to be the best attributes for distinguishing order and disorder among those tested so far.

Journal Article↗
PubMed1998

Predicting Disordered Regions from Amino Acid Sequence: Common Themes Despite Differing Structural Characterization.

Using ordered and disordered regions identified either by X-ray crystallography or by NMR spectroscopy, we trained neural networks to predict order and disorder from amino acid sequence. Although the NMR-based predictor initially appeared to be much better than the one based on the X-ray data, both predictors yielded similar overall accuracies when tested on each other's training sets, and indicated similar regions of disorder upon each sequence. The predictors trained with X-ray data showed similar results for a 5-cross validation experiment and for the out-of-sample predictions on the NMR characterized data. In contrast, the predictor trained with NMR data gave substantially worse accuracies on the out-of-sample X-ray data as compared to the accuracies displayed by the 5-cross validation during the network training. Overall, the results from the two predictors suggest that disordered regions comprise a sequence-dependant category distinct from that of ordered protein structure.

Journal Article↗
PubMed1998

Thousands of proteins likely to have long disordered regions.

Neural network predictors of protein disorder using primary sequence information were developed and applied to the Swiss Protein Database. More than 15,000 proteins were predicted to contain disordered regions of at least 40 consecutive amino acids, with more than 1,000 having especially high scores indicating disorder. These results support proposals that consideration of structure-activity relationships in proteins need to be broadened to include unfolded or disordered protein.

Amino Acid Sequence↗
PubMed1998

Protein disorder and the evolution of molecular recognition: theory, predictions and observations.

Observations going back more than 20 years show that regions in proteins with disordered backbones can play roles in their binding to other molecules; typically, the disordered regions become ordered upon complex formation. Thought-experiments with Schulz Diagrams, which are defined herein, suggest that disorder-to-order transitions are required for natural selection to operate separately on affinity and specificity. Separation of affinity and specificity may be essential for fine-tuning the molecular interaction networks that comprise the living state. For low affinity, high specificity interactions, our analysis suggests that natural selection would parse the amino acids conferring flexibility in the unbound state from those conferring specificity in the bound state. For high affinity, low specificity or for high affinity, multiple specificity interactions, our analysis suggests that the disorder-to-order transitions enable alternative packing interactions between side chains to accommodate the different binding targets. Disorder-to-order transitions upon binding also have significant kinetic implications as well, by having complex effects on both on- and off-rates. Current data are insufficient to decide on these proposals, but sequence and structure analysis on two examples support further investigations of the role of disorder-to-order transitions upon binding.

Algorithms↗
PubMed1986

The significance of digital subtraction angiography (DSA) before operative treatment of hypernephroma in a horseshoe kidney.

A case of hypernephroma in a horseshoe kidney is reported in a patient with total situs inversus organorum. The diagnostic procedures are discussed, and the significance of digital subtraction angiography for both diagnosis and treatment is emphasized, as the presentation of the arterial and venous supplies is of great value for guidance in the surgical intervention, particularly when congenital malformations are present.

Angiography↗
PubMed1975

Lead insult to the dentition in the leopard.

Fracture of developing permanent canine teeth occurred in a black leopard hospitalized for lead poisoning. Spectrographic identification of lead in soft tissue at the site of injury suggests a relationship between lead insult and the developing dentition.

Animals↗