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Can attentional theory explain the inverse base rate effect? Comment on Kruschke (2001).

In J. K. Kruschke's (2001; see record 2001-18940-005) study, it is argued that attentional theory is the sole satisfactory explanation of the inverse base rate effect and that eliminative inference (P. Juslin, P. Wennerholm, & A. Winman, 2001; see record 2001-07828-016) plays no role in the phenomenon. In this comment, the authors demonstrate that, in contrast to the central tenets of attentional theory, (a) rapid attention shifts as implemented in ADIT decelerate learning in the inverse base-rate task and (b) the claim that the inverse base-rate effect is directly caused by an attentional asymmetry is refuted by data. It is proposed that a complete account of the inverse base-rate effect needs to integrate attention effects with inference rules that are flexibly used for both induction and elimination.

Association Learning↗

NM23-H1 immunostaining is inversely associated with tumour staging but not overall survival or disease recurrence in colorectal carcinomas.

The NM23-H1 gene product has been recently identified as a potential metastasis suppressor. Studies on breast carcinomas have shown an inverse correlation between NM23-H1 status and stage of carcinogenesis and overall survival. However, in colorectal cancer, conflicting data have been reported. This study aimed to investigate whether NM23-H1 immunostaining is correlated with tumour stage, overall survival, disease recurrence, tumour differentiation, age and sex in colorectal carcinomas for the Singapore population using chi-square analysis. The staining was performed on 141 paraffin-embedded surgical specimens collected between 1991 and 1992 using a monoclonal anti-NM23-H1 antibody. Follow-up of patients was until time of death or for 5 years. There was a very significant inverse association between tumour staging and NM23-H1 status (P = 0.0004). However, NM23-H1 expression was not significantly correlated to overall 5-year survival, disease recurrence, tumour differentiation, age or sex. Thus, although NM23-H1 may be involved in suppressing metastasis, NM23-H1 immunohistochemistry has no prognostic value in colorectal cancer. This is the first report of a significant inverse association of NM23-H1 status with tumour staging in colorectal cancer which showed no correlation with overall survival or disease recurrence. Our result thus cautions against the practice of equating an inverse relation of genetic markers with tumour staging to survival or disease recurrence.

Adult↗

Lack of presystemic inversion of (R)- to (S)-ibuprofen in humans.

Presystemic inversion of (R)- to (S)-ibuprofen has been proposed but not directly examined in humans. We investigated the bioavailability of the enantiomers of ibuprofen in 10 healthy volunteers. Low-dose racemic ibuprofen (400 mg) was administered orally and intravenously (60-minute infusion), in random order. There were no significant differences between oral and intravenous doses for the area under the curve values, terminal rate constants, clearances, metabolite formation clearances, and serum protein binding for (R)- and (S)-ibuprofen. The bioavailabilities of (R)-ibuprofen and total ibuprofen were 0.92 +/- 0.11 and 0.95 +/- 0.08, respectively. The fractional inversion of (R)-ibuprofen was determined by two methods (stable isotope method and from the stereochemical composition of the urinary metabolites) that gave similar estimates of inversion for oral dosing (0.56 +/- 0.12 and 0.60 +/- 0.07, respectively) and intravenous dosing (0.56 +/- 0.09 and 0.60 +/- 0.06, respectively). We conclude that the bioavailability of both enantiomers of ibuprofen is complete and find no evidence of significant presystemic inversion.

Administration, Oral↗

An inverse transition of magnetic domain patterns in ultrathin films.

Inverse freezing and inverse melting are processes where a more symmetric phase is found at lower temperatures than at higher temperatures. Such inverse transitions are very rare. Here we report the existence of an inverse transition effect in ultrathin Fe films that are magnetized perpendicular to the film plane. The magnetization of these films is not uniform, but instead manifests itself as stripe domains with opposite perpendicular magnetization. Predictions relating to the disordering of this striped ground state in the limit of monolayer film thicknesses are controversial. Mean-field arguments predict a continuous reduction of the stripe width when the temperature is increased; other studies suggest that topological defects, such as dislocations and disclinations, might penetrate the system and induce geometrical phase transitions. We find, from scanning electron microscopy imaging, that when the temperature is increased, the low-temperature stripe domain structure transforms into a more symmetric, labyrinthine structure. However, at even higher temperatures and before the loss of magnetic order, a re-occurrence of the less symmetric stripe phase is found. Despite the widespread theoretical and experimental work on striped systems, this phase sequence and the microscopic instabilities driving it have not been observed before.

Journal Article↗

Plate-wide stress relaxation explains European Palaeocene basin inversions.

During Late Cretaceous and Cenozoic times, many Palaeozoic and Mesozoic rifts and basin structures in the interior of the European continent underwent several phases of inversion (the process of shortening a previously extensional basin). The main phases occurred during the Late Cretaceous and Middle Palaeocene, and have been previously explained by pulses of compression, mainly from the Alpine orogen. Here we show that the main phases differed both in structural style and cause. The Cretaceous phase was characterized by narrow uplift zones, reverse activation of faults, crustal shortening, and the formation of asymmetric marginal troughs. In contrast, the Middle Palaeocene phase was characterized by dome-like uplift of a wider area with only mild fault movements, and formation of more distal and shallow marginal troughs. A simple flexural model explains how domal, secondary inversion follows inevitably from primary, convergence-related inversion on relaxation of the in-plane tectonic stress. The onset of relaxation inversions was plate-wide and simultaneous, and may have been triggered by stress changes caused by elevation of the North Atlantic lithosphere by the Iceland plume or the drop in the north-south convergence rate between Africa and Europe.

Journal Article↗

Phase inversion of particle-stabilized materials from foams to dry water.

Small particles attached to liquid surfaces arise in many products and processes, including crude-oil emulsions and food foams and in flotation, and there is a revival of interest in studying their behaviour. Colloidal particles of suitable wettability adsorb strongly to liquid-liquid and liquid-vapour interfaces, and can be sole stabilizers of emulsions and foams, respectively. New materials, including colloidosomes, anisotropic particles and porous solids, have been prepared by assembling particles at such interfaces. Phase inversion of particle-stabilized emulsions from oil in water to water in oil can be achieved either by variation of the particle hydrophobicity (transitional) or by variation of the oil/water ratio (catastrophic). Here we describe the phase inversion of particle-stabilized air-water systems, from air-in-water foams to water-in-air powders and vice versa. This inversion can be driven either by a progressive change in silica-particle hydrophobicity at constant air/water ratio or by changing the air/water ratio at fixed particle wettability, and has not been observed in the corresponding systems stabilized by surfactants. The simplicity of the work is that this novel inversion is achieved in a single system. The resultant materials in which either air or water become encapsulated have potential applications in the food, pharmaceutical and cosmetics industries.

Journal Article↗

Efficacy of inverse agonists in cells overexpressing a constitutively active beta2-adrenoceptor and type II adenylyl cyclase.

1 Maximal stimulant output from the adenylyl cyclase cascade in neuroblastoma x glioma hybrid, NG108-15, cells is limited by the levels of expression of isoforms of adenylyl cyclase. Stable expression in these cells of a constitutively active mutant (CAM) version of the human beta2-adrenoceptor resulted in higher basal adenylyl cyclase activity than following expression of the human wild type beta2-adrenoceptor. Isoprenaline acted as a full agonist in membranes from both wild type and CAM beta2-adrenoceptor expressing clones. 2 Expression of type II adenylyl cyclase resulted in a substantially elevated capacity of isoprenaline to stimulate [3H]-forskolin binding, whereas in CAM beta2-adrenoceptor expressing cells the basal high affinity [3H]-forskolin binding represented a markedly greater % of the maximal effect which could be produced by addition of isoprenaline, and the EC50 for isoprenaline was some 10 fold lower than in cells expressing the wild type beta2-adrenoceptor. 3 Further transfection of the CAM beta2-adrenoceptor expressing cells with type II adenylyl cyclase greatly increased both absolute basal and agonist-stimulated levels of adenylyl cyclase activity. 4 Betaxolol, ICI 118,551, sotalol and timolol acted as inverse agonists with varying degrees of efficacy, whereas propranolol functioned as a neutral antagonist and alprenolol as a partial agonist. 5 Pretreatment of the CAM beta2-adrenoceptor and type II adenylyl cyclase expressing clones with the irreversible alkylating agent BAAM (1 microM) did not reduce the efficacy of isoprenaline but eliminated efficacy from all the inverse agonist ligands. This effect was dependent upon the concentration of BAAM employed, with half-maximal effects being produced between 10 nM and 100 nM of the alkylating agent, which is similar to the concentrations required to prevent subsequent ligand access to some 50% of the CAM beta2-adrenoceptor population. 6 These data demonstrate that inverse agonist efficacy can be modulated by receptor availability and also indicate why in physiological systems, inverse agonism can be difficult to detect.

Adenylyl Cyclases↗

Constitutive activity of the delta-opioid receptor expressed in C6 glioma cells: identification of non-peptide delta-inverse agonists.

1. G-protein coupled receptors can exhibit constitutive activity resulting in the formation of active ternary complexes in the absence of an agonist. In this study we have investigated constitutive activity in C6 glioma cells expressing either the cloned delta-(OP1) receptor (C6delta), or the cloned mu-(OP3) opioid receptor (C6mu). 2. Constitutive activity was measured in the absence of Na+ ions to provide an increased signal. The degree of constitutive activity was defined as the level of [35S]-GTPgammaS binding that could be inhibited by pre-treatment with pertussis toxin (PTX). In C6delta cells the level of basal [35S]-GTPgammaS binding was reduced by 51.9+/-6.1 fmols mg-1 protein, whereas in C6mu; and C6 wild-type cells treatment with PTX reduced basal [35S]-GTPgammaS binding by only 10.0+/-3.5 and 8.6+/-3.1 fmols mg-1 protein respectively. 3. The delta-antagonists N, N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174,864), 7-benzylidenenaltrexone (BNTX) and naltriben (NTB), in addition to clocinnamox (C-CAM), acted as delta-opioid receptor inverse agonists. Naloxone, buprenorphine, and naltrindole were neutral antagonists. Furthermore, naltrindole blocked the reduction in [35S]-GTPgammaS binding caused by the inverse agonists. The inverse agonists did not inhibit basal [35S]-GTPgammaS binding in C6mu; or C6 wild-type cell membranes. 4. Competition binding assays in C6delta cell membranes revealed a leftward shift in the displacement curve of [3H]-naltrindole by ICI 174,864 and C-CAM in the presence of NaCl and the GTP analogue, GppNHp. There was no change in the displacement curve for BNTX or NTB under these conditions. 5. These data confirm the presence of constitutive activity associated with the delta-opioid receptor and identify three novel, non-peptide, delta-opioid inverse agonists.

Animals↗

The human 5-HT7 serotonin receptor splice variants: constitutive activity and inverse agonist effects.

1. Using membranes from stably or transiently transfected HEK293 cells cultured in 5-HT-free medium and expressing the recombinant human 5-HT(7) receptor splice variants (h5-HT(7(a)), h5-HT(7(b)) and h5-HT(7(d))), we compared their abilities to constitutively activate adenylyl cyclase (AC). 2. All h5-HT(7) splice variants elevated basal and forskolin-stimulated AC. The basal AC activity was reduced by the 5-HT(7) antagonist methiothepin and this effect was blocked by mesulergine (neutral 5-HT(7) antagonist) indicating that the inhibitory effect of methiothepin is inverse agonism at the 5-HT(7) receptor. 3. Receptor density correlated poorly with constitutive AC activity in stable clonal cell lines and transiently transfected cells. Mean constitutive AC activity as a percentage of forskolin-stimulated AC was significantly higher for the h5-HT(7(b)) splice variant compared to the h5-HT(7(a)) and h5-HT(7(d)) splice variants but only in stable cell lines. 4. All eight 5-HT antagonists tested inhibited constitutive AC activity of all splice variants in a concentration-dependent manner. No differences in inverse agonist potencies (pIC(50)) were observed between the splice variants. The rank order of potencies was in agreement and highly correlated with antagonist potencies (pK(b)) determined by antagonism of 5-HT-stimulated AC activity (methiothepin >metergoline> mesulergine > or = clozapine > or = spiperone > or = ritanserin > methysergide > ketanserin). 5. The efficacy of inverse agonism was not receptor level dependent and varied for several 5-HT antagonists between membrane preparations of transiently and stably transfected cells. 6. It is concluded that the h5-HT(7) splice variants display similar constitutive activity and inverse agonist properties.

Adenylyl Cyclase Inhibitors↗

Female mating behaviour, sexual selection and chromosome I inversion karyotype in the seaweed fly, coelopa frigida

Previous studies of the seaweed fly, Coelopa frigida, have revealed the operation of several different forces of sexual selection. The overall pattern of mate choice seen in natural populations is not consistent with the predictions of indirect sexual selection as females do not express preferences that maximize the fitness of their offspring, even though the benefits from such choice are relatively large in this species. Thus, the maintenance of female mate choice for large male size must instead either be a result of a direct benefit to the female of mating with large males, or a side-effect of the evolution of another character, in other words pleiotropy. In order to separate these two alternatives the genetical basis of female mating behaviour needs to be studied. Previous studies have revealed associations between chromosomal inversion karyotype and both general female willingness to mate and mate choice for large male size, however these associations were lost after several generations of laboratory culture. Here several isokaryotypic lines from wild collections of flies were derived. The willingness to mate and mate choice of females from each line were determined. Pairs of lines of opposite inversion karyotype that significantly differed in either or both willingness to mate and mate choice were crossed. The mating behaviour and inversion karyotype of the F2 progeny (all F1 progeny are heterokaryotypes) were determined. Clear differences in the general levels of female willingness to mate were found between the two inversion homokaryotypes in several families, whereas variation in the strength of female choice for large male size were not revealed. It is suggested that mate choice in this species occurs as a pleiotropic effect of selection acting on female willingness to mate.

Journal Article↗

FG 7142 specifically reduces meal size and the rate and regularity of sustained feeding in female rats: evidence that benzodiazepine inverse agonists reduce food palatability.

Benzodiazepine receptor inverse agonists reduce food intake in males, but their actions in females, in whom stress-related eating disorders are more common, as well as their behavioral mode of action remain unclear. The consummatory effects of benzodiazepine receptor ligands have alternately been hypothesized to reflect changes in the hedonic evaluation of food or secondary effects of anxiety-related or cognitive properties. To test the anorectic mode of action of benzodiazepine inverse agonists, the effects of FG 7142 on feeding microstructure were studied in nondeprived female Wistar rats (n=32). Microstructure analysis used a novel meal definition that recognizes prandial drinking. On pharmacologically synchronized diestrus I, rats were pretreated (-30 min dark onset) with the benzodiazepine partial inverse agonist FG 7142 (i.p. 0, 3.75, 7.5, 15 mg/kg) in a between-subjects design. FG 7142 delayed the onset of (16-541%), decreased the amount eaten (36-52%) and drunk (63-87%), and reduced the time spent drinking (59-87%) within the first nocturnal meal. Dose-dependent incremental anorexia continued 6 h into the dark cycle, whereas FG 7142 did not suppress the quantity, duration or rate of drinking past the first meal. Treated rats ate smaller meals (17-42%) of normal duration. This reflected that FG 7142 slowed feeding within meals (9-38%) by decreasing the regularity and maintenance of feeding from pellet-to-pellet. FG 7142 did not influence postprandial satiety; meal frequency and inter-meal intervals were unaffected. FG 7142 anorexia was blocked by the benzodiazepine receptor antagonist flumazenil in a 2:1 molar ratio (n=17 rats). The very early, nonspecific (+10 min), but not subsequent (2.5, 4.5 h) feeding-specific phase, of FG 7142 anorexia was mirrored by anxiogenic-like behavior in FG 7142-treated (7.5 mg/kg) female rats (n=48) in the elevated plus-maze. Thus, benzodiazepine receptor inverse agonists preferentially lessen the maintenance of feeding in female rats, effects opposite to those of palatable food.

Animals↗

Digital inverse filtering for linguistic research.

To enable differences in modes of glottal vibration to be studied, glottal air volume velocity waveforms can be recovered from speech recordings by inverse filtering. Most previous published work in this area has made use of analog filters. Digital inverse filters offer many advantages, including the ability to change filter settings to match changing vocal tract filter functions. Although the theory and many of the methods necessary for digital inverse filtering have been described in the literature, a straightforward description of the entire process has been lacking. The digital inverse filtering process developed for linguistic research at the UCLA Phonetics Laboratory is described in detail in this paper, with the intention of facilitating such work at other institutions.

Analog-Digital Conversion↗

Female haemophiliac homozygous for the factor VIII intron 22 inversion mutation, with transcriptional inactivation of one of the factor VIII alleles.

Phenotypic expression of X-linked recessive disorders, including haemophilia A, is rare in females. This report describes a female with sporadic severe haemophilia A. The female patient and her family members were evaluated by coagulation assays. Visible detectable disturbance of X chromosome structure or number, as well as 2N von Willebrand disease, were excluded as possible explanations of the haemophilia A phenotype. Molecular studies, factor VIII (FVIII) intron 22 inversion mutation analysis showed that the severe haemophilia A phenotype is the result of a maternally inherited, distal, FVIII gene inversion and a paternally inherited de novo, also distal, FVIII gene inversion. Furthermore, comparative single-stranded conformation polymorphism analysis revealed the absence of detectable maternally inherited abnormal FVIII gene transcript in the patient's peripheral blood lymphocytes. X chromosome methylation analysis indicates that this could be explained by preferential inactivation of the maternally inherited X chromosome carrying the distal FVIII gene inversion.

Alleles↗

Multicopy fimB gene expression in Escherichia coli: binding to inverted repeats in vivo, effect on fimA gene transcription and DNA inversion.

Transcription of fimA, the Escherichia coli gene encoding the type 1 fimbrial subunit protein, is driven by a promoter carried on a 314 bp segment of invertible DNA. We have discovered that overexpression of fimB, one of the genes required for inversion of this DNA element, results in transcriptional repression of fimA. Furthermore, under these conditions inversion ceases to be dependent on the integration host factor (IHF) or the leucine-responsive regulatory protein (LRP), cofactors hitherto considered to be essential for inversion. Inversion will even occur (albeit at a very low level) in the absence of both cofactors. The interaction of the fimB gene product with the invertible element was studied in vivo in the presence of single- and multicopy fimB genes. Dimethyl sulphoxide (DMS)-mediated methylation of DNA at the 9 bp inverted repeats, which flank the invertible element, was found to vary in the presence and absence of functional fimB. The DMS reactivity profile at the left-hand inverted repeat was similar with single or multicopy fimB. The corresponding profile at the right-hand inverted repeat varied with fimB copy number. As this repeat lies between the fimA promoter and open reading frame, FimB binding here is likely to modulate fimA transcription and vice versa.

Bacterial Proteins↗

An inverse correlation between estimated tuberculosis notification rates and asthma symptoms.

BACKGROUND: A recent ecological analysis demonstrated a strong inverse relationship between tuberculosis notification rates and the prevalence of asthma symptoms in 13-14-year-old children as obtained from the International Study of Asthma and Allergies in Childhood (ISAAC). However, the analysis was confined to the 23 countries in which the tuberculosis notification rates were considered to be of sufficient validity. METHODS: A similar analysis was performed using estimated tuberculosis incidence rates obtained from the World Health Organization Global Tuberculosis Programme and asthma symptom prevalence data from ISAAC for both the 6-7 and 13-14 years age groups in 38 and 55 countries, respectively. RESULTS: For the 6-7-year-old children, there was a significant inverse relationship between estimated tuberculosis incidence and the prevalence of key asthma symptoms. However, in the 13-14 year age group, a significant inverse relationship was only demonstrated for 'asthma ever'. CONCLUSION: The present study extends the inverse relationship between tuberculosis rates and asthma prevalence to the 6-7-year-old age group and suggests that the association, if causal, may be stronger at this younger age.

Adolescent↗

Inversion prepared coronary MR angiography: direct visualization of coronary blood flow.

PURPOSE: Visualization of coronary blood flow by means of a slice-selective inversion pre-pulse in concert with bright-blood coronary MRA. MATERIALS AND METHODS: Coronary magnetic resonance angiography (MRA) of the right coronary artery (RCA) was performed in eight healthy adult subjects on a 1.5 Tesla MR system (Gyroscan ACS-NT, Philips Medical Systems, Best, NL) using a free-breathing navigator-gated and cardiac-triggered 3D steady-state free-precession (SSFP) sequence with radial k-space sampling. Imaging was performed with and without a slice-selective inversion pre-pulse, which was positioned along the main axis of the coronary artery but perpendicular to the imaging volume. Objective image quality parameters such as SNR, CNR, maximal visible vessel length, and vessel border definition were analyzed. RESULTS: In contrast to conventional bright-blood 3D coronary MRA, the selective inversion pre-pulse provided a direct measure of coronary blood flow. In addition, CNR between the RCA and right ventricular blood pool was increased and the vessels had a tendency towards better delineation. Blood SNR and CNR between right coronary blood and epicardial fat were comparable in both sequences. CONCLUSION: The combination of a free-breathing navigator-gated and cardiac-triggered 3D SSFP sequence with a slice-selective inversion pre-pulse allows for direct and directional visualization of coronary blood flow with the additional benefit of improved contrast between coronary and right ventricular blood pool.

Adult↗

[Puerperal inversion of the uterus].

In Europe, one inversion per 25,000 births is expected with present day obstetric management. Faulty management of the third stage of labour may increase the incidence many-fold. North American figures show that the omission of medications during the third stage of labour and traction on the umbilical cord have increased the incidence to 1 in 2,000. Whether cord traction is as free of danger as has been claimed within recent years, needs to be re-evaluated. The classical symptoms and signs of inversion of the uterus are pain, vascular shock and bleeding. If manual reposition of the uterus occurs immediately following the inversion, even without anesthesia, severe complications and post-operative morbidity are low. Following inversion of the uterus, further normal pregnancies can be expected.

Adult↗

Anomalous potentials from inverse analyses of interfacial polydisperse attractive colloidal fluids.

This paper investigates effects of using monodisperse inverse analyses to extract particle-particle and particle-surface potentials from simulated interfacial colloidal fluids of polydisperse attractive particles. Effects of polydispersity are investigated as functions of particle concentration and attractive well depth and range for van der Waals and depletion potentials. Forward Monte Carlo simulations are used to generate particle distribution functions for polydisperse interfacial colloidal fluids from which inverted potentials are obtained using an inverse Ornstein-Zernike analysis and an inverse Monte Carlo simulation method. Attractive potentials are successfully recovered for monodisperse colloidal fluids, but polydispersity that is unaccounted for in inverse analyses produces (1) apparent softening of strong forces, (2) anomalous repulsive and attractive interactions, and (3) aphysical particle overlaps. This investigation provides insights into the role of polydispersity in altering the equilibrium structure and corresponding inverted potentials of attractive colloidal fluids near surfaces. These findings should assist the design and interpretation of optical microscopy experiments involving interfacial colloidal fluids similar to the simulated experiments reported here.

Journal Article↗