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PubMed2005

Practical pulse synthesis via the discrete inverse scattering transform.

This paper provides the practical details required to use the inverse scattering (IST) approach to design selective RF-pulses. As in the Shinnar-Le Roux (SLR) approach, we use a hard pulse approximation to actually design the pulse. Unlike SLR, the pulse is designed using the full inverse scattering data (the reflection coefficient and the bound states) rather than the flip angle profile. We explain how to approximate the reflection coefficient to obtain a pulse with a prescribed rephasing time. In contrast to the SLR approach, we retain direct control on the phase of the magnetization profile throughout the design process. We give explicit recursive algorithms for computing the hard pulse from the inverse scattering data. These algorithms are quite different from the SLR recursion, being essentially discretizations of the Marchenko equations. We call our approach the discrete inverse scattering transform or DIST. Overall, it is as fast as the SLR approach. When bound states are present, we use both the left and right Marchenko equations to improve the numerical stability of the algorithm. We compute a variety of examples and consider the effect of amplitude errors on the magnetization profile.

Algorithms↗

PubMed2005

Efficacy of spectral presaturation of inversion recovery in evaluating delayed myocardial enhancement.

OBJECTIVE: Delayed myocardial enhancement is caused by a variety of cardiovascular diseases. The extent of the enhanced area has been examined by the inversion recovery (IR) method, whereby at the inversion time (TI), normal myocardium shows a low signal intensity. In this sequence, as pericardial fat shows a very high intensity, a delayed enhancement just below the pericardium may be indistinct. To improve the accuracy of delayed myocardial enhancement, we employed the spectral presaturation of inversion recovery (SPIR) method. MATERIALS AND METHODS: Thirty-five patients with symptoms of cardiovascular disease aged between 36 and 80 years old (mean age, 62 years old) were investigated. Thirty were men and five were women. Inversion recovery and SPIR images were obtained 25 min after initial administration of a gadolinium-based contrast material. Each TI, when the signal intensity of the normal myocardium was null, was determined by images obtained at serial different TIs. A radiologist and a cardiologist examined each image by a consensus reading. The extent of myocardial enhancement was described as none, subendocardial, transmural and a random pattern in each case. Images were ranked over three levels and were based on whether myocardial enhancement could be easily detected or whether the contour of the myocardium was visualized precisely. Student's t-test was conducted to compare the quality of two sequences in all patients and in 22 patients who showed delayed myocardial enhancement. RESULTS: The imaging quality in evaluating delayed myocardial enhancement in all patients was superior with IR compared with SPIR, although it was not statistically significant. The imaging quality in the patients with delayed myocardial enhancement was similar between SPIR and IR. SPIR was superior to the IR sequence in two of the four patients who exhibited transmural enhancement. CONCLUSION: SPIR exhibited equivalent image quality to IR in evaluating delayed myocardial enhancement. As it has the potential advantage in patients with rich adipose tissue surrounding the myocardium, it can be an alternative sequence to evaluate myocardial viability.

Adult↗

PubMed2006

Benzodiazepine site inverse agonists and locomotor activity in rats: bimodal and biphasic influence.

Benzodiazepine site inverse agonists may increase or decrease locomotor activity in rodents, depending on the experimental settings. We have compared the behavioral responses to environmental novelty of rats treated with the non-selective inverse agonist DMCM (2 mg/kg) and the alpha1-subunit affinity-selective inverse agonist 3-EBC (15 mg/kg). The behavior in spontaneous locomotor assay (during 45 min) and elevated plus maze (EPM) was automatically recorded. In the EPM, general activity-related parameters were similarly decreased, whereas only DMCM inhibited open-arm activity. In the locomotor assay, both compounds depressed locomotion in the first 15 min and activity in the central zone of the chamber. However, the influence of 3-EBC was less pronounced. The alpha1-subunit selective antagonist beta-CCt (15 mg/kg) attenuated locomotor depression, but not the central-zone avoidance elicited by DMCM. When habituated to the chamber, DMCM-treated animals emitted a plateau phase of activity, which disappeared by adding beta-CCt. Hence, inhibition of activity in exposed areas may be mediated by non-alpha1-subunits, whereas both alpha1 and non-alpha1-subunits may participate in suppression of activity in more protective areas of an apparatus. Hyperlocomotion in habituated animals may depend primarily on the alpha1-subunit. Moreover, the bimodal influence of inverse agonists on locomotion can be biphasic, observable in the same experiment.

Analysis of Variance↗

PubMed1997

Aging and multiple cue probability learning: the case of inverse relationships.

Multiple Cue Probability Learning (MCPL) is an important cognitive ability for all age groups that, like other cognitive abilities, depends on information processing speed and working memory capacity--skills that have been found to decline with age. The relation between age and ability to learn direct and inverse probabilistic relationships was studied in two MCPL experiments involving subjects in three age groups. In the first experiment, subjects learned two three-cue tasks following the MCPL paradigm. In the first task, all cues had a direct relation (DR) with the criterion. In the second, one cue had an inverse relation (IR) with the criterion. In the DR task, older subjects were able to learn nearly as well as younger subjects. In the IR task, older subjects performed significantly worse than younger subjects due to an inability to use the inverse cue. In a second experiment involving the IR task, task information (TI) was given, that is, the relation between each cue and the criterion was explicitly described. This eliminated the need for subjects to discover the inverse relation on their own, thus reducing the burden on working memory. Provision of TI resulted in improved performance for the 20-30 and 65-75 year old groups, but not in the 76-90 year old group. Significant differences in performance among age groups remained. These results cannot be fully explained by differences in working memory capacity. It is suggested that flexibility of functioning also plays a role.

Adult↗

PubMed1998

Serial echocardiographic assessment of left atrioventricular valve function in young children with ventricular inversion.

BACKGROUND: Regurgitation of the morphologic tricuspid valve (mTV) adversely influences the clinical outcome of patients with ventricular inversion. METHODS AND RESULTS: To evaluate the mTV regurgitation (TR), we reviewed serial echocardiograms for 25 children with ventricular inversion, with and without congenital heart surgery. Patient age was from 6 months to 19.0 (median 5.8) years. Follow-up was from 5 months to 15.0 (median 4.1) years. Initial assessment was at a median 65 days of age; only nine (36%) of 25 had TR. At follow-up, 16 (64%) of 25 had TR, with two requiring valve replacement. The mTV was abnormal in 16 (64%) of 25 patients and in 11 (69%) of 16 TR worsened compared with one (11%) of nine patients with "normal" mTVs. Nine (36%) of 25 had Ebstein's anomaly, three of whom had new TR develop. Of 17 patients who underwent cardiac surgery, 10 (59%) had new or increased TR compared with three (37%) of eight nonoperative patients. After intracardiac repairs, eight (73%) of 11 had increased TR develop compared with two (33%) of six patients after extracardiac surgery. CONCLUSIONS: (1) Young patients with ventricular inversion had TR develop during follow-up, without cardiac surgery. (2) Surgical patients with intracardiac repairs had more TR develop than with extracardiac procedures. (3) Anatomic abnormalities of the mTV were associated with an increased risk of TR developing. These data help elucidate the factors that affect the development of TR in patients with ventricular inversion.

Adolescent↗

PubMed1997

The inverse Nehb J lead increases the sensitivity of Holter electrocardiographic monitoring for detecting myocardial ischemia.

A major reason for the relatively low sensitivity of Holter electrocardiography (ECG) for detecting ischemia is that the sensitivity of bipolar leads used for Holter ischemia monitoring has not been systematically evaluated, making lead selection difficult. Therefore, this study evaluated the sensitivity of 6 bipolar Holter leads for detecting ischemia during percutaneous transluminal coronary angioplasty. Seventy-five patients, each of whom had > 1 mm ST-segment elevation on an intracoronary electrocardiogram from the myocardium distal to the stenosis during balloon occlusion, were studied for the occurrence of > or = 1 mm ST-segment elevation or depression on the simultaneously recorded Holter leads II, III, aVF, CM5, CR4, and inverse Nehb J. The study found that the inverse lead Nehb J provided a significantly higher overall sensitivity for detecting myocardial ischemia than Holter leads II, III, aVF, CM5, and CR4. Also, the use of inverse lead Nehb J significantly increased the sensitivity of 2- and 3-lead Holter ischemia monitoring. These findings were based on a significantly higher sensitivity of inverse lead Nehb J for detecting ischemia induced by transient occlusion of the left anterior descending coronary artery and a slightly higher sensitivity for detecting ischemia induced by occlusion of the left circumflex coronary artery. None of the bipolar leads studied provided a very high sensitivity for detecting ischemia induced by occlusion of the right coronary artery. These findings show that adequate lead selection can increase the sensitivity of Holter ischemia monitoring. Furthermore, the lack of a highly sensitive lead for detection of inferior ischemia indicates that further evaluation of bipolar leads is warranted.

Angioplasty, Balloon, Coronary↗

PubMed2001

Inverse relationship between microsatellite instability and K-ras and p53 gene alterations in colon cancer.

Some studies have shown an inverse relationship between microsatellite instability in colon cancer and mutations in p53 and K-ras, whereas others have not. We therefore evaluated these features in a population-based sample of 496 individuals with colon cancer. Microsatellite instability was determined by a panel of 10 tetranucleotide repeats, the Bethesda consensus panel of mono- and dinucleotide repeats, and coding mononucleotide repeats in transforming growth factor-beta receptor type II, hMSH3, BAX, hMSH6, and insulin-like growth factor receptor type II. Mutations in codons 12 and 13 in K-ras were evaluated by sequencing. p53 overexpression (as detected by immunohistochemistry) was used as an indicator of p53 mutation; this was evaluated in 275 of the tumors. K-ras mutations were present in 33.2% of tumors, p53 overexpression in 51.5%, and microsatellite instability (as determined by the Bethesda consensus panel) in 12.5%. K-ras mutations were significantly less common in unstable tumors than stable tumors (11.8% versus 36.9%, P: < 0.001). p53 overexpression was significantly less common in unstable tumors than stable tumors (20.0% versus 55.7%, P: < 0.001). These inverse relationships between microsatellite instability and ras gene mutations and p53 overexpression were shown to be independent of tumor site in logistic regression analyses. All other measures of instability also showed statistically significant inverse relationships independent of tumor site with alterations in ras and p53, and instability results determined by the panel of 10 tetranucleotide repeats were highly significantly related to those determined by the Bethesda consensus panel. Coding mononucleotide repeat mutations were significantly more common in unstable tumors than stable tumors (85.7% versus 1.0%, P: < 0.001). We conclude that there is an inverse relationship between microsatellite instability and mutations in p53 and K-ras, and that the molecular profile of colon cancers with microsatellite instability is characterized by relatively infrequent mutations in K-ras and p53 and relatively frequent mutations in coding mononucleotide repeats.

Adult↗

PubMed2003

alpha 2B-Adrenoceptor levels govern agonist and inverse agonist responses in PC12 cells.

Receptor density is an important determinant of cellular effector responses to receptor activation. We analysed cytosolic Ca(2+) responses to alpha(2)-adrenergic agents in PC12 cells expressing human alpha(2B)-adrenergic receptors (AR) at two densities (3.8 and 1.3 pmol/mg protein). The efficacy (E(max)) of agonists was greater in cells with higher receptor expression; while the potency (EC(50)) of norepinephrine and oxymetazoline was independent of alpha(2B)-AR levels. Several classical alpha(2)-AR antagonists behaved as either partial or inverse agonists in a receptor density-dependent fashion. No apparent structural similarities were found among the inverse agonists, precluding simple predictions of inverse agonist activity. Transfected PC12 cells expressing alpha(2B)-AR at relatively high density would be a useful approach to screen inverse agonists for this class of receptors. Our results further indicate that receptor density significantly influences the properties of ligands, not only of partial agonists as predicted by classical receptor theory, but also of antagonists and full agonists.

Adrenergic alpha-2 Receptor Agonists↗

PubMed2001

Agonist, antagonist, and inverse agonist properties of antipsychotics at human recombinant 5-HT(1A) receptors expressed in HeLa cells.

Agonist and antagonist properties of antipsychotics at human (h) recombinant 5-hydroxytryptamine (h5-HT(1A)) receptor have been examined previously in transfected Chinese hamster ovary (CHO) cells using 5'-O-(3-[(35)S]thio)-triphosphate ([(35)S] GTP gamma S) binding. Na(+)-dependent [35S] GTP gamma S binding to membranes from human epithelioid carcinoma (HeLa) cells, expressing 500 fmol/mg protein of h5-HT(1A) receptor (HA7 cells), appears suitable to characterize not only agonist and antagonist properties of 5-HT(1A) receptor ligands, but also inverse agonist properties. We therefore examined agonist, antagonist, and inverse agonist activity of antipsychotics at h5-HT(1A) receptor in HA7 cells. Some antipsychotics had agonist activity and stimulated [(35)S] GTP gamma S binding with the following order of efficacy: nemonapride>ziprasidone>clozapine>ocaperidone. Tiospirone and trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz[2,3:6,7,5]-oxepino-[4,5c]pyrrole (ORG 5222), were more potent h5-HT(1A) receptor antagonists than raclopride, olanzapine, and risperidone. Haloperidol, chlorpromazine, thioridazine, pimozide, and sertindole showed Na(+)-dependent inverse agonist activity at h5-HT(1A) receptor that could be antagonized by (s)-N-tert-butyl-3-(4-(2-methoxyphenyl)piperazine-1-yl)-2-phenylpropanamide [(s)-WAY 100135]. These results are further evidence that interactions with h5-HT(1A) receptors could play a role in the pharmacological profile of certain antipsychotics, and that Na(+) affects the ability to detect inverse agonist activity at h5-HT(1A) receptors, likely by influencing receptor precoupling. Also, the manner in which compounds interact with 5-HT(1A) receptors appears to be related to their K(b)/K(i) ratio.

Antipsychotic Agents↗

PubMed2003

Benzodiazepine agonist and inverse agonist coupling in GABAA receptors antagonized by increased atmospheric pressure.

Past work found that exposure to 12 times normal atmospheric pressure (ATA) of helium-oxygen gas (heliox) selectively antagonizes (uncouples) and differentiates allosteric coupling in GABA(A) receptors initiated by benzodiazepines versus neurosteroids. The present study tested the hypothesis that pressure can differentiate coupling initiated by a spectrum of benzodiazepine receptor ligands by measuring the effects of pressure on benzodiazepine ligand modulation of GABA-activated 36Cl(-) uptake in mouse brain membranes. 12 ATA completely antagonized allosteric modulation by: benzodiazepine receptor agonists diazepam and flunitrazepam; Type-1 selective benzodiazepine receptor agonist zolpidem and the benzodiazepine receptor partial inverse agonist ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-alpha][1,4]benzodiazepine-3-carboxylate (Ro15-4513). The similar, non-competitive-like characteristics of pressure antagonism of these ligands suggest common structural/functional elements underlying their coupling. Pressure also antagonized allosteric modulation by the benzodiazepine receptor inverse agonist methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), but the antagonism was not complete and appeared to be surmountable (competitive-like) suggesting unexpected differences in coupling for DMCM versus Ro15-4513. These studies represent the first attempt to use pressure as a tool to dissect benzodiazepine receptor coupling. The results suggest that there is a common, pressure antagonism sensitive structural/functional element underlying coupling for benzodiazepine receptor ligands and that coupling for the full inverse benzodiazepine receptor agonist DMCM differs from coupling for benzodiazepine receptor agonists and benzodiazepine receptor partial inverse agonists.

Animals↗

PubMed2003

Inverse sequence similarity of proteins does not imply structural similarity.

There is a debate on the folding of proteins with inverted sequences. Theoretical approaches and experiments give contradictory results. Many proteins in the Protein Data Bank (PDB) show conspicuous inverse sequence similarity (ISS) to each other. Here we analyze whether this ISS is related to structural similarity. For the first time, we performed a large scale three-dimensional (3-D) superposition of corresponding Calpha atoms of forwardly and inversely aligned proteins and tested the degree of secondary structure identity between them. Comparing proteins of less than 50% pairwise sequence identity, only 0.5% of the inversely aligned pairs had similar folds (99 out of 19073), whereas about 9% of forwardly aligned proteins in the same score and length range show similar 3-D structures (1731 out of 19248). This observation strongly supports the view that the inversion of sequences in almost all cases leads to a different folding property of the protein. Inverted sequences are thus suitable as protein-like sequences for control purposes without relations to existing proteins.

Algorithms↗

PubMed1996

Up-regulation of a constitutively active form of the beta2-adrenoceptor by sustained treatment with inverse agonists but not antagonists.

In neuroblastoma X glioma hybrid, NG1O8-15, cells transfected to stably express a constitutively active mutant (CAM) form of the human beta2-adrenoceptor, the beta-adrenoceptor ligands sotalol and betaxolol functioned as inverse agonists as they reduced basal adenylyl cyclase activity whereas the antagonists dihydroalprenolol and propranolol did not. Maintained presence of the CAMbeta2-adrenoceptor inverse agonists but not the antagonists in the culture medium of the cells resulted in a substantial, concentration-dependent, up-regulation of the CAMbeta2-adrenoceptor. Up-regulation of the CAMbeta2-adrenoceptor by the inverse agonists was prevented by co-incubation of the cells with either propranolol or dihydroalprenolol. Neither maintained elevation of cAMP levels nor the inhibition of adenylyl cyclase activity altered the ability of the inverse agonist ligands to cause receptor up-regulation.

Adrenergic beta-2 Receptor Antagonists↗

PubMed1997

Inverse sequence similarity in proteins and its relation to the three-dimensional fold.

Nowadays the most successful strategy for the prediction of the tertiary structure of proteins is the homology-based modelling using known structures. A real chance to predict the general fold of a protein arises only in cases with a sufficient sequence homology (e.g. 27% over 100 residues). In this analysis we examine the phenomenon of inverse sequence similarity (ISS) in proteins and its structural meaning. In sequence data bases we found a lot of examples for ISS up to 34% identity over 204 residues and a surprisingly large number of self-inverse protein sequences. By inspection of inverse similar sequence pairs with known tertiary structures we observe that inverse sequence alignments above the threshold indicating structural similarity generally do not imply comparable folds for both. From our analysis we conclude that the straightforward employment of ISS for protein structure prediction fails even above the known threshold for 'safe similarity'.

Amino Acid Sequence↗

PubMed2000

A sensitivity analysis of the calculation of mechanical output through inverse dynamics: a computer simulation study.

The purpose of this study was to systematically determine the effect of experimental errors on the work output calculated using two different methods of inverse dynamics during vertical jumping: (a) the conventional (rotational) method and (b) the translational method. A two-dimensional musculoskeletal model was used to generate precisely known kinematics. Next, the location of each joint center (JC) and the location of each segment's center of mass (CM) were manipulated by +/-10% of segment length to simulate errors in the location of joint centers (delta JC) and errors in the location of segment's center of mass (delta CM), respectively. Work output was subsequently calculated by applying the two methods of inverse dynamics to the manipulated kinematic data. The results showed that the translational method of inverse dynamics was less sensitive (up to 13% error in total work output) to delta JC and delta CM than the rotational method (up to 28% error in total work output). The rotational method of inverse dynamics was particularly sensitive to simulated errors in JC.

Biomechanical Phenomena↗

PubMed2003

Use of the mathematical principle of inversion in young children.

An important issue in the development of mathematical cognition is the extent to which children use and understand fundamental mathematical concepts. We examined whether young children successfully use the principle of inversion and, if so, whether they do so based on qualitative identity, length, or quantity. Twenty-four preschool children and 24 children in Grade 1 were presented with three-term inversion problems (e.g., 3+2-2) and standard problems of similar magnitude (e.g., 2+4-3). Problems were presented in three conditions to determine whether children used inversion at all and, if so, whether their decisions were based on quantitative or nonquantitative features of the problems. Both preschool and Grade 1 children showed evidence of using inversion in a fully quantitative manner, indicating that this principle is available in some form prior to extensive formal instruction in arithmetic.

Child↗

PubMed2001

Perception viewed as an inverse problem.

The modern study of perception began when Fechner published his 'Elements of Psychophysics' in 1860. This book has guided most perception research ever since. It has become increasingly clear that there are problems with Fechner's approach, which assumes that the percept is completely determined by the sensory input. Fechner's approach cannot explain the processes that allow our percepts to be veridical. Post-Fechnerian schools (Helmholtzian, Structural, Gestalt and Gibsonian) have tried to deal with this problem, but have not been successful. An alternative to the Fechnerian approach is required. This paper describes an alternative that has been developing over the last 20 years within the computer vision community. It treats perceptual interpretation as a solution of an inverse problem that depends critically on the operation of a priori constraints. Contemporary research, which adopted this approach, has concentrated on verifying the usefulness of Bayesian and standard regularization methods. This paper takes the next step; it discusses theoretical and empirical aspects of studying human perception as an inverse problem. It reviews the literature that illustrates the power of the inverse problem approach. This review leads to the suggestion that progress in the study of perception will benefit if the inverse approach were to be adopted by experimentalists, as well as by the computational modelers, who have been actively exploring its potential to date.

Bayes Theorem↗

PubMed2001

Comparison of two inversion techniques of a semi-analytical model for the determination of lake water constituents using imaging spectrometry data.

In this study, two different inversion techniques for the determination of chlorophyll-a in water were compared by a sensitivity analysis: (i) a matrix inversion method, and (ii) a curve-fitting routine. Adding white noise to the reflectance spectrum led to clearly better results for the curve-fitting routine. If, however, the atmospheric parameter visibility was not exactly known, both methods behaved similarly well. The analyses implied that the performance depended on the quality of the input spectra, the knowledge of model parameters, and also on the inversion methods, even if they were based on the same semi-analytical model. Of course, not only the uncertainties of model parameters had to be considered for the testing of the performance, but also other factors, such as processing time, implementation of the inversion algorithm, number of relevant parameters, and the application of the method to different times and different lakes.

Algorithms↗

PubMed1998

Adaptive local regularization methods for the inverse ECG problem.

One of the fundamental problems in theoretical electrocardiography can be characterized by an inverse problem. We present new methods for achieving better estimates of heart surface potential distributions in terms of torso potentials through an inverse procedure. First, we outline an automatic adaptive refinement algorithm that minimizes the spatial discretization error in the transfer matrix, increasing the accuracy of the inverse solution. Second, we introduce a new local regularization procedure, which works by partitioning the global transfer matrix into sub-matrices, allowing for varying amounts of smoothing. Each submatrix represents a region within the underlying geometric model in which regularization can be specifically 'tuned' using an a priori scheme based on the L-curve method. This local regularization method can provide a substantial increase in accuracy compared to global regularization schemes. Within this context of local regularization, we show that a generalized version of the singular value decomposition (GSVD) can further improve the accuracy of ECG inverse solutions compared to standard SVD and Tikhonov approaches. We conclude with specific examples of these techniques using geometric models of the human thorax derived from MRI data.

Algorithms↗