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PubMed1984

Recombinant cold-adapted attenuated influenza A vaccines for use in children: molecular genetic analysis of the cold-adapted donor and recombinants.

A previously described cold-adapted attenuated virus, A/Leningrad/134/17/57 (H2N2), was further modified by 30 additional passages in chicken embryos at 25 degrees C. This virus had a distinct temperature-sensitive (ts) phenotype, grew well in chicken embryos at 25 degrees C, and failed to recombine with reference ts mutants of fowl plague virus containing ts lesions in five genes coding for non-glycosylated proteins (genes 1, 2, 5, 7, and 8). Recombination of A/Leningrad/134/47/57 with wild-type influenza virus strains A/Leningrad/322/79 (H1N1) and A/Bangkok/1/79(H3N2) yielded ts recombinants 47/25/1(H1N1) and 47/7/2 (H3N2). These recombinants inherited their ts phenotype and ability to reproduce in chicken embryos at 25 degrees C from the cold-adapted parent. Analysis of the genome composition of the recombinants obtained by recombination of the cold-adapted donor with wild-type influenza virus strains A/Leningrad/322/79(H1N1) and A/Bangkok/1/79(H3N2) showed that recombinants 47/25/1(H1N1) and 47/7/2 (H3N2) inherited five and six genes, respectively, from the cold-adapted parent, and hemagglutinin and neuraminidase genes from the wild-type strains.

Animals↗

PubMed2005

Adaptive signature design: an adaptive clinical trial design for generating and prospectively testing a gene expression signature for sensitive patients.

PURPOSE: A new generation of molecularly targeted agents is entering the definitive stage of clinical evaluation. Many of these drugs benefit only a subset of treated patients and may be overlooked by the traditional, broad-eligibility approach to randomized clinical trials. Thus, there is a need for development of novel statistical methodology for rapid evaluation of these agents. EXPERIMENTAL DESIGN: We propose a new adaptive design for randomized clinical trials of targeted agents in settings where an assay or signature that identifies sensitive patients is not available at the outset of the study. The design combines prospective development of a gene expression-based classifier to select sensitive patients with a properly powered test for overall effect. RESULTS: Performance of the adaptive design, relative to the more traditional design, is evaluated in a simulation study. It is shown that when the proportion of patients sensitive to the new drug is low, the adaptive design substantially reduces the chance of false rejection of effective new treatments. When the new treatment is broadly effective, the adaptive design has power to detect the overall effect similar to the traditional design. Formulas are provided to determine the situations in which the new design is advantageous. CONCLUSION: Development of a gene expression-based classifier to identify the subset of sensitive patients can be prospectively incorporated into a randomized phase III design without compromising the ability to detect an overall effect.

Antineoplastic Agents↗

PubMed2000

An adaptive snake model for ultrasound image segmentation: modified trimmed mean filter, ramp integration and adaptive weighting parameters.

The snake model is a widely-used approach to finding the boundary of the object of interest in an ultrasound image. However, due to the speckles, the weak edges and the tissue-related textures in an ultrasound image, conventional snake models usually cannot obtain the desired boundary satisfactorily. In this paper, we propose a new adaptive snake model for ultrasound image segmentation. The proposed snake model is composed of three major techniques, namely, the modified trimmed mean (MTM) filtering, ramp integration and adaptive weighting parameters. With the advantages of the mean and median filters, the MTM filter is employed to alleviate the speckle interference in the segmentation process. The weak edge enhancement by ramp integration attempts to capture the slowly varying edges, which are hard to capture by conventional snake models. The adaptive weighting parameter allows weighting of each energy term to change adaptively during the deformation process. The proposed snake model has been verified on the phantom and clinical ultrasound images. The experimental results showed that the proposed snake model achieves a reasonable performance with an initial contour placed 10 to 20 pixels away from the desired boundary. The mean minimal distances from the derived boundary to the desired boundary have been shown to be less than 3.5 (for CNR > or = 0.5) and 2.5 pixels, respectively, for the phantom and ultrasound images.

Algorithms↗

PubMed1995

Evidence for two sites of adaptation affecting the dark-adapted ERG of cats and primates.

The present study compared the effects of full-field steady adapting backgrounds on the sensitivity of the scotopic threshold response (STR) of the dark-adapted ERG and scotopic PII (b-wave and d.c.-component) to Ganzfeld flashes in cats (n = 4), macaque monkeys (n = 2), and one human subject. In cats, the sensitivity of the STR was reduced by a factor of 2 by backgrounds that were 500 times weaker than backgrounds reducing PII; and for the primates, the STR was reduced by backgrounds almost 100 times weaker than those reducing PII. Since the STR is generated more proximally in the retina than PII, these results provide evidence for proximal and more distal retinal sites of postreceptoral light adaptation. A practical implication is that dim scattered room light can remove the STR from the ERG while hardly affecting PII.

Adaptation, Ocular↗

PubMed1999

Light adaptation and dark adaptation of human rod photoreceptors measured from the a-wave of the electroretinogram.

1. We recorded the a-wave of the human electroretinogram from subjects with normal vision, using a corneal electrode and ganzfeld (full-field) light stimulation. From analysis of the rising phase of rod-isolated flash responses we determined the maximum size (amax) of the a-wave, a measure of the massed circulating current of the rods, and the amplification constant (A) of transduction within the rod photoreceptors. 2. During light adaptation by steady backgrounds the maximal response was reduced, as reported previously. amax declined approximately as I0/(I0 + IB), where IB is retinal illuminance and I0 is a constant. In different subjects I0 ranged from 40 to 100 trolands, with a mean of 70 trolands, corresponding to about 600 photoisomerizations s-1 per rod. (1 troland is the retinal illuminance that results when a surface luminance of 1 cd m-2 is viewed through a pupil area of 1 mm2.) The amplification constant A decreased only slightly in the presence of steady backgrounds. 3. Following a full bleach amax recovered along an S-shaped curve over a period of 30 min. There was no detectable response for the first 5 min, and half-maximal recovery took 13-17 min. 4. The apparent amplification constant decreased at early times after large bleaches. However, upon correction for reduced light absorption due to loss of pigment, with regeneration of rhodopsin occurring with a time constant of 9-15 min in different subjects, it appeared that the true value of A was probably unchanged by bleaching. 5. The recovery of amax following a bleach could be converted into recovery of equivalent background intensity, using a 'Crawford transformation' derived from the light adaptation results. Following bleaches ranging from 10 to > 99 %, the equivalent background intensity decayed approximately exponentially, with a time constant of about 3 min. 6. The time taken for amax to recover to a fixed proportion of its original level increased approximately linearly (rather than logarithmically) with fractional bleach, with a slope of about 12 min per 100 % bleach. Similar behaviour has previously been seen in psychophysical dark adaptation experiments, for the dependence of the 'second component' of recovery on the level of bleaching.

Adaptation, Ocular↗

PubMed1991

[Study on choroidal blood flow at dark and light adaptation. II. Choroidal blood flow at light adaptation].

The effect of light adaptation on choroidal blood flow (CBF) was studied in albino rabbits. CBF was measured by the hydrogen clearance method. There was no significant change of CBF at light adaptation, in which CBF had been expected to decrease due to decreased oxygen demand of the outer retina. The results showed that light adaptation did not influence CBF, in spite of the close relationship between the outer retina and choroidal circulation. Because of the rich blood flow, the choroidal circulation may not need a reaction mechanism for functional changes of the outer retina.

Adaptation, Ocular↗

PubMed1982

Dark-adapted sensitivity, rhodopsin content, and background adaptation in pcd/pcd mice.

Adaptation to steady background lights has been investigated in pcd/pcd mice, a mutant strain with retinal degeneration. The hyperbolic stimulus/response functions of the scotopic b-wave of the electroretinogram show progressive changes. For the dark-adapted eyes the decrease in log sensitivity between ages 1 and 12 months is related linearly to the decreasing rhodopsin content. The observed decline in amplitude of maximum responses from dark-adapted eyes begins only after age 5 months and is accompanied by gradual prolongation of the time to the peak of half-maximum b-wave responses. At all ages, the sensitivity of response is changed little by increments of steady red background lights; the greatest slope of log sensitivity vs. log background plots is about +0.2. (In normal mice the slope is about +0.9.) The pcd/pcd b-wave results do not fit the normal empirical relation that is thought to reflect neural processing in the distal retina. Thus the present results suggest that neural processing is abnormal in pcd/pcd retinas.

Adaptation, Physiological↗

PubMed1988

Adaptation in chemoreceptor cells. I. Self-adapting backgrounds determine threshold and cause parallel shift of response function.

1. The self-adapting effects of chemical backgrounds on the response of primary chemoreceptor cells to superimposed stimuli were studied using lobster (Homarus americanus) NH4 receptor cells. 2. These receptors responded for several seconds to the onset of the backgrounds, and then returned to their initial level of spontaneous activity (usually zero). The strongest response always occurred only during the steepest concentration change; the response then decayed back to zero or to the earlier spontaneous firing level, while the background concentration was still rising, and remained silent during the entire time that the background was maintained constant (20-30 min) 3. Exposure to constant self-adapting backgrounds eliminated the response of NH4 receptor cells to stimuli of concentration lower than the background, and reduced the responses to all higher stimulus concentrations tested by a nearly equal amount. This resulted in a parallel shift of the stimulus-response function to the right along the abscissa. 4. Since the response threshold was completely re-set by adaptation to backgrounds, NH4 receptors seem to function mostly as detectors of relative rather than absolute stimulus intensity across their entire dynamic range: the response to a given stimulus-to-background ratio remained the same over 3 log step increases of background concentration. 5. As in other sensory modalities, a parallel shift of response functions appears to be an important property of chemoreceptor cells, allowing for this sensory system to function over a wider stimulus intensity range than the instantaneous dynamic range of individual receptor cells.

Action Potentials↗

PubMed1982

Dark adaptation with interposed white adapting fields.

It is proposed that dark adaptation following a moderate pigment bleach may nearly as well be carried out (and more conveniently) under low room lighting conditions as in complete darkness. To test this idea, dark adaptation curves were determined either immediately after the termination of a 3 min, 4.1 log td white pre-exposure field, or following 10 or 15 min of additional exposure to one of three low-level photopic (2.9, 2.4, 1.8 log td) backgrounds of white light. Dark thresholds measured after the additional exposure fell rapidly and reached the rod plateau of the normal dark adaptation curve with a maximal delay of 1.5 min (for the 10 min backgrounds) or 6.5 min (for the 15 min backgrounds). For the time to be spent in the dark, this meant a savings of 8.5 min. At smaller delays savings were even greater. The difference between savings and delay indicates whether or not an interposed background is feasible.

Dark Adaptation↗

PubMed1978

Adaptation of biological membranes to temperature. The lack of homeoviscous adaptation in the sarcoplasmic reticulum.

Temperature adaptation of biological membranes was examined by comparing the fragmented sarcoplasmic reticulum preparation of goldfish acclimated to different temperatures. Membrane fluidity was estimated using the fluorescence polarization technique. There was considerable variation between preparations, but no consistent differences in fluidity were observed between 5- and 25 degrees C-acclimated goldfish, fish species adapted over an evolutionary period to arctic or desert temperatures, and rat. The fatty acid composition of the sarcoplamic reticulum preparations of differently acclimated goldfish showed differences in the proportion of mono- and polyunsaturated fatty acids while the proportion of saturated fatty acids remained relatively constant. However, the fatty acid composition of sarcoplasmic reticulum phosphoglycerides became more unsaturated in the order rat, desert pupfish, arctic sculpin, which correlates with their respective environmental or body temperature. It is concluded that differences in membrane components other than fatty acids are important in determining membrane dynamic structure. The inability to demonstrate homeoviscous adaptation in sarcoplasmic reticulum is supported by other evidence suggesting that functions of the sarcoplasmic reticulum that are measured in vitro are not affected by such modifications of their phosphoglyceride fatty acid composition as occur during thermal acclimation.

Adaptation, Biological↗

PubMed1982

Color perception under chromatic adaptation: equilibrium yellow and long-wavelength adaptation.

Observers viewed a thin (0.8-1.3) annulus composed of a mixture of 540 and 660 nm monochromatic lights (denoted delta G and delta R, respectively). The annular mixture was superimposed upon a larger (2.7) 660 nm circular background field. The observer adjusted the radiance of either delta G or delta R so that the annulus appeared a perfect (i.e. neither reddish nor greenish) yellow. In the first experiment, the background and annulus both were presented steadily. The results showed that the background, varied over a range from 10 to 1000 td. always contributed less to the color appearance of the annular test area than would be expected from the simple admixture of lights. The second experiment examined the effect of briefly removing the background-field quanta during the period when the annulus was judged. After several minutes of adapting to the background, the background was momentarily extinguished for 1 sec once every 6 sec; the observer adjusted the radiance of delta R so that during the 1 sec period the continuously presented annular mixture appeared equilibrium yellow. With steady backgrounds, the delta G to delta R luminance ratio decreased with test annulus luminance; for judgments made while the background momentarily was extinguished, the luminance ratio generally increased with annulus luminance. All of the empirical observations can be accounted for quantitatively by a two-process theory of chromatic adaptation; in two processes are (1) gain changes and (2) a restoring signal that tends to drive back toward equilibrium the opponent response resulting from the adapting light. Results from a third experiment, in which the background-off interval was reduced from 1 sec to 500, 200 or 150 msec. also are consistent with this model.

Adaptation, Ocular↗

PubMed1994

Cytogenetic adaptive response with multiple small X-ray doses in mouse germ cells and its biological influence on the offspring of adapted males.

Cytogenetic adaptive response of mouse germ cells was studied by exposing male mice to a sequence of 4 conditioning doses of 0.05 Gy each (D1) administered at 10-day intervals and subsequently to a single challenging dose of 1.5 Gy (D2). In concurrent experiments, male mice after treatment with D1 doses alone were mated to unirradiated females and the F1 males were given the D2 dose. Chromosomal aberrations in both spermatocytes and bone-marrow cells and UV-induced UDS in splenocytes of these mice were studied. Adapted mice (i.e., D1 + D2 exposures) responded with a significantly lower frequency of chromosomal aberrations than the non-adapted (D2 exposure only) controls. The relative reduction in frequencies was, however, similar to that observed in earlier work with a single conditioning dose of 0.05 Gy. The frequencies of chromosomal aberrations in spermatocytes and bone-marrow cells as well as the levels of UV-induced UDS in splenocytes of the F1 males in the group D1 to fathers + D2 to F1 males were the same as those in F1 males which received only the D2 exposure.

Adaptation, Physiological↗

PubMed1993

Gonadotropin-releasing hormone, a neuropeptide of efferent projections to the teleost retina induces light-adaptive spinule formation on horizontal cell dendrites in dark-adapted preparations kept in vitro.

The teleost retina receives efferent projections from neurons of the nucleus olfactoretinalis at the base of the olfactory bulbs. These fibres contain gonadotropin-releasing hormone (GnRH) immunoreactive material and are presynaptic to retinal dopaminergic interplexiform cells. We have incubated isolated dark-adapted retinae and eyecup preparations of roach with salmon-GnRH and found an increase in horizontal cell spinule numbers to 70% light-adaptive levels. This effect was blocked by addition of haloperidol to the incubation medium suggesting that GnRH acts via stimulation of the dopaminergic interplexiform cells. We conclude that GnRH containing efferent fibres are capable of inducing light-adaptive changes in the retina and discuss their implication in the control of endogenous rhythms.

Amino Acid Sequence↗

PubMed2006

The role of the posterior parietal lobe in prism adaptation: Failure to adapt to optical prisms in a patient with bilateral damage to posterior parietal cortex.

We studied a patient (J.J.) with bilateral damage to those regions of the posterior parietal cortex (PPC) thought to be involved in prism adaptation. We demonstrated, for the first time in a parietal patient, that J.J. was unable to adapt to the visual perturbation induced by the optical prisms with either hand within four times the number of trials required by healthy adult subjects. We offer a novel account for the role of the PPC in prism adaptation: that the reach direction to the veridical target location specified in extrinsic limb-based coordinates must be de-coupled from the gaze direction to the perceived target location specified by intrinsic oculocentric coordinates in order to produce spatially accurate movements. This spatial discrepancy between gaze direction and reach direction may provide the necessary training signal required by the cerebellum to update the current internal model used to maintain spatial congruency between visual and proprioceptive maps of peripersonal space. The hypothesis is discussed in relation to recent disconnectionist accounts of optic ataxia.

Adaptation, Physiological↗

PubMed2002

Evolution in Hawaiian cave-adapted isopods (Oniscidea: Philosciidae): vicariant speciation or adaptive shifts?

We assessed evolutionary relationships among Hawaiian cave-adapted isopods using a maximum-likelihood criterion to analyze cytochrome oxidase I nucleotide sequences. Results support morphological data that two genera of philosciid isopods have invaded caves independently in the islands. In the genus Littorophiloscia, a sister relationship between a surface-dwelling species, L. hawaiiensis, and an undescribed cave species was corroborated. This evidence, along with the known parapatric distributions between species, supports a speciation event by an adaptive shift on the island of Hawaii from a marine littoral to a terrestrial subterranean habitat. The monophyletic genus Hawaiioscia contains four known obligate cave-dwelling species, each of which occurs on a separate island. However, despite present-day allopatric distributions between Hawaiioscia species, the geographic and phylogenetic patterns are not sufficient to support a vicariant mode of speciation. Instead, we believe that the known species of Hawaiioscia evolved from a widespread ancestral surface species or a group of closely related species through multiple, independent adaptive shifts on each of the islands of Kauai, Oahu, Molokai, and Maui. This is the first molecular investigation of evolutionary relationships between surface-dwelling and cavernicolous arthropods in Hawaii and it suggests that simple vicariance is insufficient to explain the evolution of troglobites in tropical zones.

Adaptation, Physiological↗

PubMed1979

Salt taste adaptation: the psychophysical effects of adapting solutions and residual stimuli from prior tastings on the taste of sodium chloride.

The paper reviews how adaptation to sodium chloride, changing in concentration as a result of various experimental procedures, affects measurements of the sensitivity, intensity, and quality of the salt taste. The development of and evidence for the current model that the salt taste depends on an adaptation level (taste zero) determined by the sodium cation concentration is examined and found to be generally supported, despite great methodological complications. It would seem that lower adaptation levels elicit lower thresholds, higher intensity estimates, and altered quality descriptions with predictable effects on psychophysical measures.

Adaptation, Physiological↗

PubMed1979

Adaptation and cross-adaptation to odor stimulation of olfactory receptors in the tiger salamander.

We have used the effects of self- and cross-adaptation on the unitary responses of olfactory receptors of the tiger salamander to odor stimulation to investigate the stimulus-specific components of these responses and to provide information about the cross-cell variations in the numbers and numbers of types of constitutent receptive sites. An olfactometer delivered sequential odorous pulses, either juxtaposed or separated by a variable time delay. We used four pairs of odorants judged to be similar within a given pair. The unitary response to the test stimulation relative to that of the conditioning stimulation varied from being unchanged to being completely eliminated. We sometimes observed substantial poststimulus increases in the firing rate following stimulation with juxtaposed odorous pulse. Except in the case of one odorant pair, cross-adaptation occurred both with juxtaposed pulses and with pulses separated in time. With the methyl butyrate/ethyl butyrate odorant pair, however, statistically significant cross-adaptation appeared only with juxtaposed pulses. We propose a simple model to aid in explaining these phenomena. The experimental observations in conjunction with this model are used to obtain estimates of the maximal and minimal number of receptive site types available for interaction with the chosen odorants.

Action Potentials↗

PubMed1969

Dark adaptation: an interocular light-adaptation effect.

Presentation of iight to the left eye simultaneously with adaptation of the right eye to light may accelerate dark adaptation in the right eye. The result is that the rod-cone-break and the final threshold of the rods are achieved earlier than when the right eye alone is adapted to light.

Adaptation, Ocular↗