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PubMed2005

Generalized DQE analysis of radiographic and dual-energy imaging using flat-panel detectors.

Analysis of detective quantum efficiency (DQE) is an important component of the investigation of imaging performance for flat-panel detectors (FPDs). Conventional descriptions of DQE are limited, however, in that they take no account of anatomical noise (i.e., image fluctuations caused by overlying anatomy), even though such noise can be the most significant limitation to detectability, often outweighing quantum or electronic noise. We incorporate anatomical noise in experimental and theoretical descriptions of the "generalized DQE" by including a spatial-frequency-dependent noise-power term, S(B), corresponding to background anatomical fluctuations. Cascaded systems analysis (CSA) of the generalized DQE reveals tradeoffs between anatomical noise and the factors that govern quantum noise. We extend such analysis to dual-energy (DE) imaging, in which the overlying anatomical structure is selectively removed in image reconstructions by combining projections acquired at low and high kVp. The effectiveness of DE imaging in removing anatomical noise is quantified by measurement of S(B) in an anthropomorphic phantom. Combining the generalized DQE with an idealized task function to yield the detectability index, we show that anatomical noise dramatically influences task-based performance, system design, and optimization. For the case of radiography, the analysis resolves a fundamental and illustrative quandary: The effect of kVp on imaging performance, which is poorly described by conventional DQE analysis but is clarified by consideration of the generalized DQE. For the case of DE imaging, extension of a generalized CSA methodology reveals a potentially powerful guide to system optimization through the optimal selection of the tissue cancellation parameter. Generalized task-based analysis for DE imaging shows an improvement in the detectability index by more than a factor of 2 compared to conventional radiography for idealized detection tasks.

Algorithms↗
PubMed1983

Single-channel fluctuations in bimolecular lipid membranes induced by rat olfactory epithelial homogenates.

Chemosensitive single-channel fluctuations were observed to be induced in essentially solvent-free lipid bimolecular membranes by the addition of sonicated homogenates of rat olfactory epithelium. The chemosensitive channels were not observed when respiratory epithelium homogenates were used instead. Ionic selectivity is consistent with potassium ions as the charge carrier. These channels may be associated with the initial events of chemoreception in the rat olfactory epithelium.

Animals↗
PubMed1994

Consciousness: function and definition.

The term "consciousness" plays an enormous role in the clinical assessment of patients and also in psychophysiological considerations. It has often been said that consciousness is a term that defies definition. This lack of definability, however, might be more apparent than real. In the multitude of facets, three main components can be singled out: a) vigilance, b) mental contents and c) selective attention. Vigilance, not to be equated with consciousness, is most amenable to electrophysiological studies. The stages of sleep have fairly well standardized EEG correlates, unlike the comatose states. The overflowing wealth of mental contents is constantly adjusted to momentary needs by the mechanism of selective attention. Awareness is a subcomponent and differs from both vigilance and consciousness. Emotionality is particularly important among the variety of further subcomponents. The time factor must be taken into account in order to understand the dynamics and fluctuations of consciousness.

Animals↗
PubMed2005

Tolcapone: a review of its use in the management of Parkinson's disease.

Tolcapone (Tasmar) is a selective, reversible inhibitor of peripheral and central catechol-O-methyltransferase (COMT). Results of well designed studies indicate that oral tolcapone is an effective adjunct to levodopa plus a peripheral dopa-decarboxylase inhibitor (DDCI) in patients with fluctuating Parkinson's disease. Tolcapone significantly improves levodopa-induced motor fluctuations and significantly reduces levodopa requirements. The drug is generally well tolerated, with the most commonly occurring adverse events being dopaminergic related. Thus, tolcapone is a useful option in patients with fluctuating Parkinson's disease who are receiving levodopa/DDCI and are not responding to, or are not candidates for, other adjunctive treatments.

Antiparkinson Agents↗
PubMed1982

Observer variability in grading patients with subarachnoid hemorrhage.

The management of individual patients with subarachnoid hemorrhage depends greatly on assessment of the patient's clinical condition. Difficulty in applying current grading systems prompted the authors to conduct studies of observer variability and to attempt to identify sources of inconsistency. Observers graded 15 patients by both the Hunt and Hess and Nishioka systems. Considerable observer variability was found, with up to four different grades being selected for the same patient. Kappa statistics were used to evaluate the data. This method determines observer agreement occurring in excess of chance. Kappa values for each grading system showed observer agreement to be significantly better than chance, yet revealed marked observer variation. Most variation occurred when Grade 3 was selected, irrespective of the system used. In a further study where observers graded clinical summaries, similar variation occurred; therefore, inconsistency was due mainly to difficulty in matching patients with levels described in the grading system, rather than to fluctuation in the patient's clinical condition or difference in the observers' examination technique. Variability was high when patients with systemic disease or vasospasm on angiography were graded with the Hunt and Hess system. The studies show that a simpler and more reliable grading system is required, and emphasize and need for caution when interpreting the results from different published series.

Adult↗
PubMed1996

Effect of a prenylamine analog (MG8926) on spontaneous action potentials in isolated rabbit sinoatrial node.

Effects of verapamil, prenylamine and a prenylamine analog, MG8926 on the intracellular spontaneous action potentials recorded from the isolated rabbit sinoatrial (SA) node were studied. Verapamil (1 microM), a selective inhibitor for slow Ca2+ channels, prolonged the cycle length, decreased the rate of diastolic depolarization, the rate of rise of action potential, the amplitude of action potential and the maximal diastolic potential, and usually arrested showing subthreshold fluctuation of the membrane potential within several ten min. Prenylamine (10 microM), a nonselective inhibitor for slow Ca2+ channels, tended to prolong the cycle length to decrease the diastolic depolarization, the rate of rise of action potential, the amplitude of action potential. However, these changes were statistically insignificant. Prenylamine at the concentration of 10 microM had no effect on the maximal diastolic potential. MG8926 (10 microM) prolonged the cycle length, decreased the rate of diastolic depolarization, the rate of rise of action potential and tended to decrease the amplitude of action potential. MG8926 at the concentration of 10 microM had almost no effect on the maximal diastolic potential. The present findings may indicate that replacement of phenyl residue of prenylamine by cyclohexyl residue increases the inhibitory action on the slow Ca2+ channels in rabbit SA node.

Action Potentials↗
PubMed2002

Correlated response of autogeny to selection for adult starvation resistance in the blowfly, Lucilia cuprina.

We withheld sucrose from adults in three lineages of Lucilia cuprina, producing a four-fold greater mortality than in control lineages, in order to impose direct selection for carbohydrate starvation resistance. The frequency of autogeny (maturation of eggs in the absence of adult protein feeding) increased as a correlated response by an average of 4.9 to 9.2% per generation in three lineages subjected to starvation over five generations. The frequency of autogeny fluctuated but did not display a significant net change in three control lineages. Autogeny in L. cuprina seems to behave as a threshold trait, with a continuous, genetically-based underlying disposition producing discrete phenotypes. The heritability of autogeny in our laboratory lineages was estimated to be 0.09 to 0.39, 0.04 to 0.36, and -0.08 to 0.30 (95% confidence intervals). Despite the potential for autogeny to evolve and despite protein limitation of female fecundity in Australian populations of L. cuprina, the trait is rare or absent in the field. Genetic variation for autogeny may be maintained, but at sub-threshold levels, by nutrient availability in the field, while trade-offs associated with autogeny probably limit the net fitness benefit of the trait and prevent the evolution of a noticeable frequency of autogenous females.

Animals↗
PubMed2005

Potential selectin L ligands involved in selective recruitment of peripheral blood CD16(-) natural killer cells into human endometrium.

Unique CD16(-) natural killer (NK) cells appear in the human cycling endometrium and acutely increase in number after ovulation. Selective recruitment from peripheral blood (PB) CD16(-) NK cells is a potential mechanism for the postovulatory increase of these NK cells. The interaction between selectin L, an adhesion molecule playing a critical role in leukocyte extravasation, and its ligands may be involved in this phenomenon. We investigated the menstrual cycle-dependent fluctuation of selectin L expression on PB CD16(-) NK cells and selectin L ligand expression in the human endometrial endothelium. The expression of selectin L on PB CD16(-) NK cells was constantly high throughout the menstrual cycle compared with other PB CD16(+) NK cells and non-NK lymphocytes. Among eight selectin L ligands examined, podocalyxin-like, mucosal addressin cell adhesion molecule-1 (MADCAM1) and chondroitin sulfate proteoglycan 2 (CSPG2) were localized in the endometrial endothelium. Semiquantitative score of immunostaining intensity in the endometrial endothelium for MADCAM1 was highest in the late secretory phase, whereas that for CSPG2 peaked throughout the secretory phase. There was a strong positive correlation between the number of endometrial NK cells and the semiquantitative score for CSPG2. Three active isoforms of CSPG2 mRNA were detected in the human endometrium. These findings support the idea that the interaction between selectin L and selectin L ligands functions in the postovulatory selective recruitment of PB CD16(-) NK cells into the human endometrium.

Adult↗
PubMed1986

Maternal metabolism and teratogenesis in zinc-deficient rats.

Embryos removed at 11.5 days gestation from pregnant rats allowed a zinc-deficient diet from the time of mating showed a high frequency of malformations of all organ systems. There were, however, large differences between litters of individual dams. Comparison of the daily food intake of zinc-deficient dams with the appearance of the embryos suggested that fluctuations in the maternal serum zinc levels induced by feeding or fasting influenced the availability of zinc to the embryos. By cyclically feeding zinc-deficient dams to a predetermined schedule, low maternal serum zinc levels were induced at selected stages of development. This was accompanied by specific malformations of the organs developing at that time.

Abnormalities, Multiple↗
PubMed1986

Linear and nonlinear effects in the interactions of motor units and muscle spindle afferents.

Successive motor unit (MU) twitches often do not sum linearly. Also, muscle spindle (MS) afferents may react nonlinearly to MU contractions occurring at short intervals. Little data is presently available on the interactions between two (or more) MUs regarding their effects on tension output and MS responses. We have studied these effects in cat Mm. gastrocnemius medialis (MG), soleus and semitendinosus. In adult anaesthetized cats, MUs of the muscle under study were electrically stimulated via their ventral root axons with random sequences of brief pulses having mean rates between 6 and 12 pulses per second. Isometric tension fluctuations were recorded from the muscle under study, and discharge patterns of MS afferents (Ia and group II) were recorded from dorsal root filaments. A cross-correlation analysis was performed to display linear and nonlinear effects evoked by selected time constellations of MU activations. 18 (67%) of 27 MG MUs showed marked potentiation of the second of two twitches in response to pairs of stimuli separated by 5 to about 25 ms. The remainder of these and 16 of the soleus MUs did not exhibit conspicuous nonlinearities. MS responses to such pairs of MU activations usually showed a prolonged spindle pause. About 28% of 36 pairs of MG MUs produced twitch tension less than expected for linear summation if activated nearly simultaneously. If two MUs both produced a spindle pause and possibly a relaxation discharge in an MS afferent, the near-synchronous activation of the units produced respective discharge variations that were less than expected for linear summation. If one MU produced an early discharge, contraction of another MU would often prevent it. These results are discussed in regard to mechanisms of tremor suppression.

Animals↗
PubMed1978

[The myogenic basis of smooth muscle motility (author's transl)].

Many mammalian smooth muscle tissues are able to produce spontaneous, myogenic activity. Five types of phasic-rhythmic activity can be distinguished: 1) Spikes: brief depolarizations of the membrane which trigger calcium release and contraction; 2) oscillations of the membrane potential of the second-rhythm type (SR) generating the spikes; 3) various organ-specific rhythms such as gastric and ureteral peristalsis which can be grouped together as basic organ-specific rhythms (BOR); 4) slower fluctuations of the minute-rhythm type (MR); 5) an hour-rhythm (HR) as the slowest type. In addition, some tissues generate tonic activity by special processes which can operate without spike discharges of the cell membrane. A selective blockade of phasic and tonic components is possible with some members of the group of so-called calcium antagonists. This indicates that two different calcium activation systems exist in the membrane of smooth muscle cells (P- and T-systems). Selective P- and T-blockade offers new possibilities for pharmacological influences on the smooth muscle system.

Animals↗
PubMed2005

A review of the factors affecting the survival of donkeys in semi-arid regions of sub-Saharan Africa.

The large fluctuations seen in cattle populations during periods of drought in sub-Saharan Africa are not evident in the donkey population. Donkeys appear to have a survival advantage over cattle that is increasingly recognized by smallholder farmers in their selection of working animals. The donkey's survival advantages arise from both socioeconomic and biological factors. Socioeconomic factors include the maintenance of a low sustainable population of donkeys owing to their single-purpose role and their low social status. Also, because donkeys are not usually used as a meat animal and can provide a regular income as a working animal, they are not slaughtered in response to drought, as are cattle. Donkeys have a range of physiological and behavioural adaptations that individually provide small survival advantages over cattle but collectively may make a large difference to whether or not they survive drought. Donkeys have lower maintenance costs as a result of their size and spend less energy while foraging for food; lower energy costs result in a lower dry matter intake (DMI) requirement. In donkeys, low-quality diets are digested almost as efficiently as in ruminants and, because of a highly selective feeding strategy, the quality of diet obtained by donkeys in a given pasture is higher than that obtained by cattle. Lower energy costs of walking, longer foraging times per day and ability to tolerate thirst may allow donkeys to access more remote, under-utilized sources of forage that are inaccessible to cattle on rangeland. As donkeys become a more popular choice of working animal for farmers, specific management practices need to be devised that allow donkeys to fully maximize their natural survival advantages.

Africa South of the Sahara↗
PubMed1992

Different susceptibility of red cell membrane proteins to calpain degradation.

The presence of low levels of calpastatin activity in erythrocytes of hypertensive rats affects regulation of calpain activity so it is highly susceptible to activation within physiological fluctuations in [Ca2+]. Under identical conditions, in red cells of normotensive rats, calpain activation is efficiently controlled by the high levels of calpastatin activity, and a progressive increase in proteinase activity can only be observed in parallel with a decrease in the level of calpastatin. In intact erythrocytes from hypertensive rats exposed to small variations in [Ca2+], degradation of anion transport protein (band 3) and Ca(2+)-ATPase appears as a primary event indicating that these two transmembrane proteins are probably early recognized as targets of intracellular calpain activity. Furthermore, band 3 protein seems to be structurally modified in erythrocytes from hypertensive rats, as indicated by its increased susceptibility to degradation in the presence of 10-50 microM Ca2+. In addition, when exposed to progressive and limited increases in [Ca2+], erythrocytes from hypertensive rats, but not those from normotensive rats, show a high degree of fragility that can be restored to normal values by inhibition of calpain. These results indicate that, within fluctuations in [Ca2+] close to physiological values, regulation of calpain activity is efficiently accomplished in normal erythrocytes but is completely lost in cells from hypertensive animals. Regulation is of critical importance in maintaining normal structural and functional properties of selective red cell membrane and cytoskeletal proteins, among which band 3 and Ca(2+)-ATPase appear to be the substrates with highest susceptibility to digestion by calpain.

Animals↗
PubMed2002

The nuclear pore complex mystery and anomalous diffusion in reversible gels.

The exchange of macromolecules between the cytoplasm and the nucleus of eukaryotic cells takes place through the nuclear pore complex (NPC), which contains a selective permeability barrier. Experiments on the physical properties of this barrier appear to be in conflict with current physical understanding of the rheology of reversible gels. This paper proposes that the NPC gel is anomalous and characterized by connectivity fluctuations. It develops a simplified model to demonstrate the possibility of enhanced diffusion constants of macromolecules trapped in such a gel.

Biological Transport, Active↗
PubMed2004

From molecular noise to behavioural variability in a single bacterium.

The chemotaxis network that governs the motion of Escherichia coli has long been studied to gain a general understanding of signal transduction. Although this pathway is composed of just a few components, it exhibits some essential characteristics of biological complexity, such as adaptation and response to environmental signals. In studying intracellular networks, most experiments and mathematical models have assumed that network properties can be inferred from population measurements. However, this approach masks underlying temporal fluctuations of intracellular signalling events. We have inferred fundamental properties of the chemotaxis network from a noise analysis of behavioural variations in individual bacteria. Here we show that certain properties established by population measurements, such as adapted states, are not conserved at the single-cell level: for timescales ranging from seconds to several minutes, the behaviour of non-stimulated cells exhibit temporal variations much larger than the expected statistical fluctuations. We find that the signalling network itself causes this noise and identify the molecular events that produce it. Small changes in the concentration of one key network component suppress temporal behavioural variability, suggesting that such variability is a selected property of this adaptive system.

Adaptation, Physiological↗
PubMed2000

Long-Term Experimental Evolution in Escherichia coli. VIII. Dynamics of a Balanced Polymorphism.

We describe the short- and long-term dynamics of a phenotypic polymorphism that arose in a population of Escherichia coli while it was serially propagated for almost 20,000 generations in a glucose-limited minimal medium. The two types, designated L and S, differ conspicuously in the size of the colonies they form on agar plates as well as the size of their individual cells, and these differences are heritable. The S type reached a detectable frequency (>1%) at generation 6,000, and it remained above that frequency throughout the subsequent generations. In addition to morphological differences, L and S diverged in important ecological properties. With clones isolated at 18,000 generations, L has a maximal growth rate in fresh medium that is ∼20% higher than that of S. However, experiments with conditioned media demonstrate that L and S secrete one or more metabolites that promote the growth of S but not of L. The death rate of L during stationary phase also increases when S is abundant, which suggests that S may either secrete a metabolite that is toxic to L or remove some factor that enables the survival of L. One-day competition experiments with the clones isolated at generation 18,000 show that their relative fitness is frequency dependent, with each type having an advantage when rare. When these two types are grown together for a period of several weeks, they converge on an equilibrium frequency that is consistent with the 1-d competition experiments. Over the entire 14,000-generation period of coexistence, however, the frequency of the S type fluctuated between approximately 10% and 85%. We offer several hypotheses that may explain the fluctuations in this balanced polymorphism, including the possibility of coevolution between the two types.

Escherichia coli↗
PubMed1995

Hypoxia-activated prodrugs as antitumour agents: strategies for maximizing tumour cell killing.

1. Hypoxia arises in solid tumour because of inefficient blood supply. While hypoxic cells are resistant to radiotherapy and probably to many chemotherapeutic drugs they can, in principle, be turned to advantage through the development of hypoxia-activated cytotoxic drugs (bioreductive drugs). 2. Three general approaches to exploiting tumour hypoxia are discussed. The first relies on fluctuating blood flow in tumours and the consequent cycling of cells through the hypoxic compartment. The second incorporates a prodrug approach in which drug activation gives rise to cytotoxic metabolites which diffuse out of hypoxic zones. The third utilizes selective inhibitors of tumour blood flow to induce additional hypoxia and thus enhance bioreductive drug activation. 3. The latter two approaches are illustrated by recent studies with the dinitrobenzamide nitrogen mustard class of bioreductive drugs and their combination with the tumour blood flow inhibitor 5,6-dimethylxanthenone-4-acetic acid.

Aniline Mustard↗
PubMed2004

Honey bee nest thermoregulation: diversity promotes stability.

A honey bee colony is characterized by high genetic diversity among its workers, generated by high levels of multiple mating by its queen. Few clear benefits of this genetic diversity are known. Here we show that brood nest temperatures in genetically diverse colonies (i.e., those sired by several males) tend to be more stable than in genetically uniform ones (i.e., those sired by one male). One reason this increased stability arises is because genetically determined diversity in workers' temperature response thresholds modulates the hive-ventilating behavior of individual workers, preventing excessive colony-level responses to temperature fluctuations.

Animals↗