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Biomedical subjects

A Hayes

Publications and source records attributed to A Hayes.

At least 19 recordsLinked to original sources

Transcript analysis of 1003 novel yeast genes using high-throughput northern hybridizations.

The expression of 1008 open reading frames (ORFs) from the yeast Saccharomyces cerevisiae has been examined under eight different physiological conditions, using classical northern analysis. These northern data have been compared with publicly available data from a microarray analysis of the diauxic transition in S.cerevisiae. The results demonstrate the importance of comparing biologically equivalent situations and of the standardization of data normalization procedures. We have also used our northern data to identify co-regulated gene clusters and define the putative target sites of transcriptional activators responsible for their control. Clusters containing genes of known function identify target sites of known activators. In contrast, clusters comprised solely of genes of unknown function usually define novel putative target sites. Finally, we have examined possible global controls on gene expression. It was discovered that ORFs that are highly expressed following a nutritional upshift tend to employ favoured codons, whereas those overexpressed in starvation conditions do not. These results are interpreted in terms of a model in which competition between mRNA molecules for translational capacity selects for codons translated by abundant tRNAs.

Blotting, Northern↗

Sensitivity to contrast histogram differences in synthetic wavelet-textures.

Recent research on texture synthesis suggests that characterisation of those properties of textures to which human observers are sensitive may be provided by the histograms of the coefficients of a wavelet decomposition. In this study we examined the properties of wavelet histograms that affect texture discrimination by measuring observer sensitivity to differences in the wavelet histograms of synthetic textures. The textures, generated via Gabor micropattern synthesis, were broadband, with amplitude spectra that are characteristic of natural images, i.e. 1/f. We measured texture-difference thresholds for three moments of the wavelet histograms -- variance, skew and kurtosis -- by manipulating the contrast, phase, and density, of the Gabor elements used to construct the textures. Observers discriminated more efficiently between textures that had differences in kurtosis, than between textures that had differences in either variance or skew. Performance was compared to two model observers; one used the pixel-luminance histogram, the other used the histogram of the output of wavelet-filters. The results support the idea that the visual system is relatively sensitive to the kurtosis, or 4th moment, of the wavelet histogram of textures. We argue that higher than 4th-order moments will, in practice, become increasingly difficult for the visual system to represent because the lack of a perfect match between the elements and the receptive fields effectively blurs the response histogram, thereby attenuating higher moments.

Contrast Sensitivity↗

A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations.

A large proportion of the 6,000 genes present in the genome of Saccharomyces cerevisiae, and of those sequenced in other organisms, encode proteins of unknown function. Many of these genes are "silent, " that is, they show no overt phenotype, in terms of growth rate or other fluxes, when they are deleted from the genome. We demonstrate how the intracellular concentrations of metabolites can reveal phenotypes for proteins active in metabolic regulation. Quantification of the change of several metabolite concentrations relative to the concentration change of one selected metabolite can reveal the site of action, in the metabolic network, of a silent gene. In the same way, comprehensive analyses of metabolite concentrations in mutants, providing "metabolic snapshots," can reveal functions when snapshots from strains deleted for unstudied genes are compared to those deleted for known genes. This approach to functional analysis, using comparative metabolomics, we call FANCY-an abbreviation for functional analysis by co-responses in yeast.

Adenine Nucleotides↗

Comparison of the effects of two early intervention strategies on the health outcomes of malnourished hemodialysis patients.

OBJECTIVE: To determine the efficacy and cost-effectiveness of providing oral supplementation early in the course of malnutrition for hemodialysis (HD) patients. DESIGN: The study design consisted of 3 groups: an experimental group, a control group of patients with mild hypoalbuminemia (HA) (serum albumin [SA] = 3.5 to 3.7 g/dL), and a comparison group of patients with moderate to severe HA (SA = 2.5 to 3.4 g/dL). SETTING: Ten outpatient hemodialysis centers in southeast lower Michigan. PATIENTS: Treatment and control groups consisted of 32 HD patients with mild HA. Fourteen HD patients with moderate to severe HA comprised the comparison group. INTERVENTION: The experimental group received diet counseling and oral supplementation, and the control group received diet counseling only. The comparison group received physician-prescribed oral supplements and dietary counseling to permit comparison of the experimental treatment with current supplementation practices. MAIN OUTCOME MEASURES: Differences between groups in the number of patients reaching nutritional repletion, change in SA levels at the end of the study, and follow-up periods, were tested using chi-square analysis. Analysis of variance was used to compare group differences in treatment duration to repletion and number of hospitalization days. RESULTS: During the study period, significantly more patients reached nutritional repletion in the experimental group and control group (50% and 57%, respectively) than in the comparison group (7%). Overall, repletion occurred more quickly in the experimental group (3.2 +/- 1.7 months) than in the control group (3.5 +/- 1.2 months), with a larger number of patients in the experimental group repleted by month 2 of the study phase. During follow-up, patients in the experimental group were far more likely to maintain nutritional repletion or continue to improve (61%) than patients in the control group (14%). Although too few patients were hospitalized to show statistical significance, there was a trend toward greater numbers of hospital days in more malnourished patients (208 days for the comparison group), followed by those with mild HA who did not receive oral supplements (107 days), and the experimental group (71 days). CONCLUSION: Although the sample size for this study was too small for the results to be conclusive, it appears that use of nutritional supplements early in the course of malnutrition may provide benefits such as, attaining nutritional repletion more quickly, which results in less product usage. It is also more likely that good nutritional status will be maintained after supplementation is discontinued.

Aged↗

Charged-particle multiplicity near midrapidity in central Au+Au collisions at sqrt[SNN]=56 and 130 GeV.

We present the first measurement of pseudorapidity densities of primary charged particles near midrapidity in Au+Au collisions at sqrt[s(NN)] = 56 and 130 GeV. For the most central collisions, we find the charged-particle pseudorapidity density to be dN/deta|(|eta|<1) = 408+/-12(stat)+/-30(syst) at 56 GeV and 555+/-12(stat)+/-35(syst) at 130 GeV, values that are higher than any previously observed in nuclear collisions. Compared to proton-antiproton collisions, our data show an increase in the pseudorapidity density per participant by more than 40% at the higher energy.

Journal Article↗

Apparent position governs contour-element binding by the visual system.

An assumption inherent in many models of visual space is that the spatial coordinates of retinal cells implicitly give rise to the perceptual code for position. The results of the experiments reported here, in which it is shown that retinally non-veridical locations of contour elements are used by the visual system for contour-element binding, lend support to a different view. The visual system does not implicitly code position with reference to the labelled locations of retinal cells, but dynamically extracts spatial position from the aggregate result of local computations. These computations may include local spatial relationships between retinal cells, but are not confined to them; other computations, including position derived from local velocity cues, are combined to code the position of objects in the visual world.

Form Perception↗

Coherent global motion in the absence of coherent velocity signals.

It is widely believed that form and motion are analysed separately in mammalian visual systems. Form is confined within a stream that projects ventrally from V1 to the inferotemporal cortex, and motion within a stream that projects more dorsally, to the posterior parietal cortex [1] [2] [3] [4] [5] [6] [7]. Current descriptions suggest that there is little contact between the two streams until the products of their separate analyses are bound together at a late (and still unidentified) stage in perception [3] [8] [9] [10]. There are, however, indications that form and motion signals may interact [11], and that form signals, streaks derived from motion, may assist in the analysis of its direction [12]. Lennie [13] proposes that all image attributes, form and motion included, remain intimately coupled within the same retinotopic map at all stages of visual analysis. Here we show that form, independent of motion, can give coherence to incoherent motion. Sequences of Glass patterns [14] built to a common global rule are devoid of coherent motion signals, but they produce motion consistent with the global rule for form, not with the random velocity components of the pattern sequence.

Animals↗

Functional analysis of eight open reading frames on chromosomes XII and XIV of Saccharomyces cerevisiae.

Deletion, together with basic functional and bioinformatic analyses has been carried out on eight novel ORFs discovered during the sequencing of the Saccharomyces cerevisiae genome. Six ORFs (YLL049w, YLL051c, YLL052c, YLL053c, YLL054c and YLL055w) located on the left arm, and one (YLR130c) on the right arm, of chromosome XII, and an eighth ORF (YNL331c) on the left arm of the chromosome XIV, have been investigated. ORFs were deleted by the SFH-PCR gene-replacement strategy. Basic functional analysis revealed no obvious phenotype for any of the eight ORFs. Bioinformatic analysis, however, revealed possible functions for seven of the ORFs on the basis of the amino acid sequence similarity of their predicted protein products to those of proteins with known functions. ORF YLL051c (FRE6) shows similarity to iron transport proteins, such as ferric reductase. YLL052c and YLL053c appear to be aquaporins. The product of YLL054c (Yll054p) is highly similar to the oleate-specific transcriptional activator protein (Pip2p), which is involved in the peroxisomal induction pathway (pip). ORF YLL055w is similar to Dal5p, allantoate permease, and may play role in allantoin transport. YLR130c (ZRT2) is a low-affinity zinc transporter protein. YNL331c is also named AAD14, which is induced by chemicals that induce oxidative stress by depleting the cell of glutathione.

Chromosomes, Fungal↗

Effects of LIF dose and laminin plus fibronectin on axotomized sciatic nerves.

Leukemia inhibitory factor (LIF), a cytokine which has neurotrophic and myotrophic activities, has been shown to enhance nerve regeneration and consequent return of muscle function in the entubulation model of sciatic nerve repair. Fibronectin (FN) and laminin (LN) are two extracellular matrix (ECM) components that, when combined, promote axon growth in the entubulation model. The aim of this study was to determine the optimal LIF dose and the efficacy of FN plus LN administered either alone or simultaneously with the optimal LIF dose. We found that at 12 weeks following nerve repair, a single 10 ng LIF dose produced the largest medial gastrocnemius (MG) muscle mass (P < 0.0001) and maximum force contraction (P < 0.001). The diameter of the axons in the FN plus LN group were significantly greater than for saline (P < 0.001) and the LIF dose groups (P < 0.01). When 10 ng LIF was combined with FN plus LN, the MG muscle mass was significantly greater than the optimal LIF dose (P < 0.05), suggesting an additive effect. Our findings support the view that combinations of factors, which perhaps act on complementary mechanisms for nerve regeneration, will be required to maximally potentiate nerve regeneration and return of muscle function after nerve injury.

Animals↗

Functional properties of regenerating skeletal muscle following LIF administration.

We tested the hypothesis that periodic systemic administration of the myogenic cytokine leukemia inhibitory factor (LIF) enhances the functional recovery of regenerating skeletal muscle following bupivacaine-induced degeneration. LIF had no effect on functional capacity or regenerating myofiber size in rat muscles at 7, 14, or 21 days post-injury. The results do not support exogenous administration of LIF as a treatment for acute muscle injury, but a more frequent dosing regimen should be tested.

Animals↗

Anaesthesia in myotubular (centronuclear) myopathy.

A patient with a known history of myotubular myopathy presented for surgery for insertion of a tibial nail. Anasthesia was induced and maintained using an intravenous anasthetic technique. Neuromuscular function was assessed using mechanomyography, which showed a profound reduction in muscle contractility. In view of this, the use of muscle relaxants was avoided altogether. Nerve conduction was normal but electromyography showed small motor units, with generalised distribution, suggesting mild to moderately severe myopathy. The patient made a slow but uneventful recovery.

Anesthesia, Intravenous↗

Comparison of recovery following rapacuronium, with and without neostigmine, and succinylcholine.

The neuromuscular blocking effects of a single dose of rapacuronium 1.5 mg x kg(-1) with or without reversal with neostigmine have been examined in the present study and compared with a dose of succinylcholine 1.0 mg x kg(-1). Neuromuscular block was measured mechanomyographically using train-of-four stimulation. Complete block occurred within 1 min with both agents. Twenty-five per cent recovery of the first response of the train-of-four occurred in a median [range] time of 7.6 [5.7-11.3] min in the succinylcholine group and in 14.2 [8.8-23.6] and 15.1 [9.6-23.4] min in the rapacuronium groups with and without neostigmine reversal, respectively. Spontaneous recovery to a train-of-four ratio of 0.8 took 33.4 [20.0-79.0] min with rapacuronium but this was reduced to about 21.2 [13.9-33.7] min when neostigmine was administered at 25% recovery of first twitch of the train-of-four.

Adolescent↗

An experimental comparison of viewpoint-specific and viewpoint-independent models of object representation.

Four experiments that investigate the cognitive representation of objects in human observers are reported. Two broad classes of theory were examined: viewpoint-specific and viewpoint-independent models. The former postulate that the data structures underpinning object recognition correspond to discrete views and require additional processing to access them from unfamiliar viewpoints. The latter postulate data structures that are independent of any particular viewpoint and can be directly accessed from a wide range of viewpoints. Two experimental tasks were used: a sequential matching paradigm and a cognitive learning paradigm. Findings favour viewpoint-specific models over viewpoint-independent models.

Adult↗

Conceptual modelling of genomic information.

MOTIVATION: Genome sequencing projects are making available complete records of the genetic make-up of organisms. These core data sets are themselves complex, and present challenges to those who seek to store, analyse and present the information. However, in addition to the sequence data, high throughput experiments are making available distinctive new data sets on protein interactions, the phenotypic consequences of gene deletions, and on the transcriptome, proteome, and metabolome. The effective description and management of such data is of considerable importance to bioinformatics in the post-genomic era. The provision of clear and intuitive models of complex information is surprisingly challenging, and this paper presents conceptual models for a range of important emerging information resources in bioinformatics. It is hoped that these can be of benefit to bioinformaticians as they attempt to integrate genetic and phenotypic data with that from genomic sequences, in order to both assign gene functions and elucidate the different pathways of gene action and interaction. RESULTS: This paper presents a collection of conceptual (i.e. implementation-independent) data models for genomic data. These conceptual models are amenable to (more or less direct) implementation on different computing platforms.

Computational Biology↗

A comparison of regularly administered sustained release oral morphine with intramuscular morphine for control of postoperative pain.

UNLABELLED: We studied the efficacy and side effect profile of regularly administered, oral sustained-release morphine sulfate tablets (MST) and IM morphine in patients undergoing total hip arthroplasty under lumbar spinal anesthesia. Patients in Group I received MST 20 mg 12 hourly and a placebo IM injection 6 hourly regularly. Group II patients received an oral placebo 12 hourly and morphine sulfate 10 mg IM 6 hourly regularly. Rescue analgesia was provided with regular diclofenac suppositories and patient-controlled analgesia. Pain scores assessed by using visual analog scale and verbal pain scoring at rest and with movement were low in both groups, with no statistical difference between groups. Mean patient-controlled analgesia morphine consumption during the 48-h study was 16.7 mg in the IM group and 25.9 mg in the MST group. The difference between the groups was significant at 36 h postoperatively (0.03). Side effects of sedation and respiratory depression were not problematic in either group, with a maximal sedation score of 2 occurring once in a patient in Group II. Nausea and vomiting occurred more often in Group II, but this was not statistically significant, with a mean nausea/vomiting score for Group II of 1.7. We conclude that oral, sustained-release morphine is an attractive alternative to IM opiates in patients undergoing body surface surgery under regional anesthesia. IMPLICATIONS: Each postoperative analgesic has its own limitations for route of administration, dosage, and potential side effects. Using the oral route for drug administration seems more attractive than other methods but may not be suitable in all postoperative patients. We studied the efficacy and side effect profile of sustained-release, oral morphine compared with standard IM morphine for the treatment of pain after hip replacement surgery. We concluded that use of the oral preparation is a suitable alternative to the IM route in this population undergoing surgery under spinal anesthesia.

Administration, Oral↗

The roles of polarity and symmetry in the perceptual grouping of contour fragments.

We describe two experiments that investigate the roles of polarity and symmetry in the perceptual grouping of contour fragments. Observers viewed, for one second on each presentation, arrays of oriented, spatial-frequency band-pass, elements, in which a subset of the elements was aligned along a twisting curve. In each of five conditions we measured observers' ability to detect aligned combinations of even- and odd-symmetric elements, of the same and different polarities, against a background of 'noise' elements. As with previous experiments we found that the 'path' could be reliably detected, even when the elements of the path were oriented at angles of up to +/- 60 deg relative to each other. Detection of the path was still possible when the polarity of path elements alternated. However, the probability of detection of the path was raised significantly when the path elements were all of the same polarity. Perceptual grouping of even-symmetric elements was no different to perceptual grouping of odd-symmetric elements. The results provide evidence, that in achieving integration of contour fragments, the visual system uses a process that is to some degree phase selective. We use the results to describe how the visual system may resolve natural contours when they occur against backgrounds that vary over a wide range of intensities. The data presented here have been published in conference-abstract form (Hayes et al., 1993; Field et al., 1997).

Dark Adaptation↗

Transcript analysis of 250 novel yeast genes from chromosome XIV.

The European Functional Analysis Network (EUROFAN) is systematically analysing the function of novel Saccharomyces cerevisiae genes revealed by genome sequencing. As part of this effort our consortium has performed a detailed transcript analysis for 250 novel ORFs on chromosome XIV. All transcripts were quantified by Northern analysis under three quasi-steady-state conditions (exponential growth on rich fermentative, rich non-fermentative, and minimal fermentative media) and eight transient conditions (glucose derepression, glucose upshift, stationary phase, nitrogen starvation, osmo-stress, heat-shock, and two control conditions). Transcripts were detected for 82% of the 250 ORFs, and only one ORF did not yield a transcript of the expected length (YNL285w). Transcripts ranged from low (62%), moderate (16%) to high abundance (2%) relative to the ACT1 mRNA. The levels of 73% of the 206 chromosome XIV transcripts detected fluctuated in response to the transient states tested. However, only a small number responded strongly to the transients: eight ORFs were induced upon glucose upshift; five were repressed by glucose; six were induced in response to nitrogen starvation; three were induced in stationary phase; five were induced by osmo-stress; four were induced by heat-shock. These data provide useful clues about the general function of these ORFs and add to our understanding of gene regulation on a genome-wide basis.

Blotting, Northern↗