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At least 505 records · Page 28Linked to original sources

Raman mapping of low-content API pharmaceutical formulations. I. Mapping of Alprazolam in Alprazolam/Xanax tablets.

PURPOSE: Raman chemical imaging of API was carried out to provide information on whether there is any structural difference between the commercial Xanax and Alprazolam tablets (the API content less than 1% w/w in both cases) in the batches with low and good recovery. MATERIALS AND METHODS: Raman mapping spectra were collected from the flattened surfaces of six tablets. The mapping spectra were analyzed by principal component analysis because the Raman signal of the API (Alprazolam) was not reliably detected from the raw spectra. The complexity of the obtained grey-scale score images was such that no information about the domain sizes of the API could be obtained and thus binarization was applied to simplify these images. RESULTS: It was found that reliable detection of the Raman signal of the API was only achieved after principal component analysis was employed with the mapping being facilitated by a surprising similarity between a high principal component loading and the spectrum of the API. The binarization was successful only if the outlying pixels in the score images are eliminated. SUMMARY: The final chemical images represent quantitative characterization of the domains of the API in the tablets in contrast to chemical images of tablets that have been reported so far in the literature which have usually been descriptive only. The abundance of Alprazolam in all six tablets of Xanax and Alprazolam, respectively, was very similar. The domain sizes were found to be below 75 mum in diameter for all the tablets analyzed.

Alprazolam↗

Application of body surface mapping to exercise testing: S-T80 isoarea maps in patients with coronary artery disease.

Body surface electrocardiographic maps were recorded before and after exercise in 25 men with angiographically documented coronary disease. Torso potential distributions at 192 locations were derived from a 32 lead electrode array using methods previously described in our laboratory. The S-T segment was characterized by the spatial distribution of the integral of S-T segment voltage over 80 ms (S-T80). Body surface regions where the S-T80 areas were =8 mV . ms or greater were identified in 18 of 25 patients. The most negative S-T80 site on the map was called the "S-T80 minimum." The S-T80 minima were located 1 or 2 electrode rows away from the standard V4--V6 electrode positions in 6 of 18 patients who developed S-T80 areas of -8 mV . ms or greater. Our data suggest that standard electrocardiographic leads may not be optimal for identifying S-T segment depression in all patients with coronary disease. Furthermore, body surface mapping during exercise provides a more quantitative and qualitative method for characterizing the ischemic response to exercise.

Adult↗

Representation of the visual streak in visuotopic maps of the cat's superior colliculus: influence of the mapping variable.

A series of visuotopic maps has been prepared from recordings of electrical potentials related to W-cell afferent activity in the cat's superior colliculus. These maps clearly exhibit an expected exaggeration of the representation of the upper visual field, due to tilt of the retina's visual streak in the 'position of paralysis'. This asymmetry disappears when the visual field's coordinate system is rotated by an angle equal to the tilt of the axis of the nasal streak. Previously published maps, based on recordings from postsynaptic collicular units, have failed to reflect this tilt of the nasal visual streak, perhaps in part because the centers of unit receptive-fields are biased estimators of the retinal origin of axons terminating near a collicular recording site.

Animals↗

Stress causes induction of MAP kinase-specific phosphatase and rapid repression of MAP kinase activity in Drosophila.

Heat shock and chemical stress induce activation of heat shock (stress) genes and synthesis of heat shock proteins. It is not yet fully understood which molecular mechanism leads to activation. Probably denatured proteins play an important role in activating the transcription factor (HSF), but on the other hand there are many hints that a phosphorylation event is involved, too. During a search for a possible signal transduction system in Drosophila Schneider 2 cells we analysed the response of the mitogen-activated protein (MAP) kinase after stress and its regulation by phosphatases. We show here that stress activates a MAP kinase-specific phosphatase in Drosophila and inhibits MAP kinase activity.

8-Bromo Cyclic Adenosine Monophosphate↗

Precordial ST-segment mapping. 4. Experience with mapping of ST-segment depression in anterior transmural myocardial infarction.

In order to assess the relative significance of precordial ST-segment elevations and depressions, 32 patients with anterior transmural myocardial infarction were studied utilizing serial 49-lead precordial maps. Theoretically, zones of ST-segment depression adjacent to major zones of ST-segment elevation might represent border areas of mild ischemia, and hence could be more readily amenable to intervention therapy. As expected, an extensive zone of ST-segment elevation was observed precordially in each of these patients. However, zones of ST-segment depression in adjacent areas were noted to occur inconsistently, were limited in distribution and magnitude, and bore no fixed relationship to zones of ST-segment elevation. Thus, mapping of precordial ST-segment depression in anterior transmural infarction probably has a limited role in assessing evolution of ischemic injury or therapy in these patients. This finding does not, however, vitiate the significance of ST-segment depressions in angina, intermediate coronary syndrome, or non-transmural infarction, conditions which may deserve further study using mapping techniques.

Adult↗

The CCAAT/enhancer binding protein (C/EBP alpha) gene (CEBPA) maps to human chromosome 19q13.1 and the related nuclear factor NF-IL6 (C/EBP beta) gene (CEBPB) maps to human chromosome 20q13.1.

The CEBPA gene encoding CCAAT/enhancer binding protein (C/EBP alpha) has been mapped to human chromosome 19 and the CEBPB (formerly TCF5) gene encoding NF-IL6 (C/EBP beta) to human chromosome 20 by Southern blot analysis of Chinese hamster x human and mouse x human somatic cell hybrids. CEBPA has been further mapped to 19q13.1 between the loci GPI and TGFB using human x hamster somatic cell hybrids containing restricted fragments of human chromosome 19. This position was confirmed by fluorescence in situ hybridization. Furthermore, CEBPB has been mapped to 20q13.1 by fluorescence in situ hybridization.

Animals↗

Method for obtaining a high resolution protein map starting from a low resolution map.

A method is described for estimating the phases of high resolution single-crystal diffraction data from proteins, by using as a starting point a set of low resolution phases (about 3 A) derived by multiple isomorphous replacement (or other) methods. The method consists in refining by least-squares the positions and thermal parameters of a set of dummy atoms placed in the initial low resolution electron density map, so as to minimize the discrepancy between the calculated scattering intensities and the scattering intensities observed in the high resolution data set. Phases calculated from these refined atomic positions are used to extend the resolution and to improve the quality of the electron density map. The success of the method depends on a new least-squares algorithm that has a radius of convergence of about 0.75 A. This large radius of convergence, together with the severe restrictions placed on the initial positions of the dummy atoms by the requirement that they lie within limited regions of the isomorphous electron density map, and the constraint imposed by the polymeric nature of a polypeptide chain account for the success of the method. The method has been successfully used to phase the structure factors of 2-zinc insulin at a resolution of 2 A and 1.5 A, starting from a set of isomorphous phases at 3-A resolution.

Insulin↗

Pulmonary lymphatic mapping in dogs: use of technetium sulfur colloid and isosulfan blue for pulmonary sentinel lymph node mapping in dogs.

Lung cancer is the most frequent cause of cancer death in the United States. The pattern of regional lymph node involvement is a major prognostic factor in a patient with nonsmall cell lung cancer. The accuracy of information obtained about the lymph node status of lung cancer patients can be potentially increased by sentinel node lymphatic mapping. This technique has been well studied in melanoma and breast cancer. It may be useful in increasing the detection of micrometastases and in decreasing the morbidity from complete mediastinal lymphadenectomy. We report an animal pilot study of pulmonary lymphatic mapping. The aim of our study was to gain experience in the surgical techniques for pulmonary sentinel node lymphatic mapping in an animal model prior to its application in humans. Technetium sulfur colloid and isosulfan blue dye were injected into different lobes of the lung followed by attempts to identify the sentinel node draining that specific portion of the lung. Technetium sulfur colloid identified the sentinel node in five of six dogs within 20 min after the radiotracer was injected into the lung parenchyma. Isosulfan blue dye identified the sentinel node in three of six dogs within 5 min. Both the agents are potentially useful, but we found greater technical ease in identifying the sentinel node with technetium sulfur colloid. Two single-institution pilot studies in humans have been performed. A multicentered study to validate and further refine this technique is necessary. Advanced pathologic techniques such as immunohistochemistry and reverse transcriptase-polymerase chain reaction can be used to enhance the accuracy of staging. This may facilitate proper application of novel therapeutic strategies to improve the current dismal prognosis of this disease.

Animals↗

Dominant mutations of Drosophila MAP kinase kinase and their activities in Drosophila and yeast MAP kinase cascades.

Eight alleles of Dsor1 encoding a Drosophila homologue of mitogen-activated protein (MAP) kinase kinase were obtained as dominant suppressors of the MAP kinase kinase kinase D raf. These Dsor1 alleles themselves showed no obvious phenotypic consequences nor any effect on the viability of the flies, although they were highly sensitive to upstream signals and strongly interacted with gain-of-function mutations of upstream factors. They suppressed mutations for receptor tyrosine kinases (RTKs); torso (tor), sevenless (sev) and to a lesser extent Drosophila EGF receptor (DER). Furthermore, the Dsor1 alleles showed no significant interaction with gain-of-function mutations of DER. The observed difference in activity of the Dsor1 alleles among the RTK pathways suggests Dsor1 is one of the components of the pathway that regulates signal specificity. Expression of Dsor1 in budding yeast demonstrated that Dsor1 can activate yeast MAP kinase homologues if a proper activator of Dsor1 is coexpressed. Nucleotide sequencing of the Dsor1 mutant genes revealed that most of the mutations are associated with amino acid changes at highly conserved residues in the kinase domain. The results suggest that they function as suppressors due to increased reactivity to upstream factors.

Alleles↗

Mapping of nascent light and heavy strand transcripts on the physical map of HeLa cell mitochondrial DNA.

The sequences complementary to the nascent RNA molecules isolated from transcription complexes of HeLa cell mtDNA have been mapped on the H and L strands of mtDNA by the S1 protection technique. The distribution of these sequences among different Hpa II restriction fragments was found to reflect the position of these fragments in the Hpa II map of mtDNA. Thus, the S1-resistant hybrids formed with the L strand corresponded almost exclusively to the right half of the genome past the origin of replication in the direction of L strand transcription, and were especially concentrated in the region immediately adjacent to the origin. By contrast, the hybrid duplexes involving the H strand appeared to be localized in the left half of the genome, and in particular in the quadrant of the map adjacent to the origin in the direction of H strand transcription. These results strongly suggest that the region of mtDNA around the origin of replication contains an initiation site for L strand transcription and an initiation site for H strand transcription.

Base Sequence↗

Quartet-mapping, a generalization of the likelihood-mapping procedure.

Likelihood-mapping (LM) was suggested as a method of displaying the phylogenetic content of an alignment. However, statistical properties of the method have not been studied. Here we analyze the special case of a four-species tree generated under a range of evolution models and compare the results with those of a natural extension of the likelihood-mapping approach, geometry-mapping (GM), which is based on the method of statistical geometry in sequence space. The methods are compared in their abilities to indicate the correct topology. The performance of both methods in detecting the star topology is especially explored. Our results show that LM tends to reject a star tree more often than GM. When assumptions about the evolutionary model of the maximum-likelihood reconstruction are not matched by the true process of evolution, then LM shows a tendency to favor one tree, whereas GM correctly detects the star tree except for very short outer branch lengths with a statistical significance of >0.95 for all models. LM, on the other hand, reconstructs the correct bifurcating tree with a probability of >0.95 for most branch length combinations even under models with varying substitution rates. The parameter domain for which GM recovers the true tree is much smaller. When the exterior branch lengths are larger than a (analytically derived) threshold value depending on the tree shape (rather than the evolutionary model), GM reconstructs a star tree rather than the true tree. We suggest a combined approach of LM and GM for the evaluation of starlike trees. This approach offers the possibility of testing for significant positive interior branch lengths without extensive statistical and computational efforts.

Computer Simulation↗

Rayleigh-Bénard percolation transition of thermal convection in porous media: computational fluid dynamics, NMR velocity mapping, NMR temperature mapping.

Stationary thermal convection and heat conduction were studied in random-site percolation clusters in a Rayleigh-Bénard configuration experimentally by NMR microscopy techniques and numerically with the aid of a finite volume method. The porosity of the percolation clusters, and the temperature difference applied to the convection cell were varied. Two-dimensional percolation networks were generated with the aid of a random-number algorithm. The resulting clusters were used as templates for the fabrication of model objects. The convective velocity distribution of silicon oil or ethylene glycol filled into the pore space was mapped and evaluated in the form of histograms. The flow patterns visualized in the simulated and the measured velocity maps show good coincidence. In the histograms, two velocity regimes can be distinguished and attributed to local convection rolls responsible for the low-velocity part, and cluster-spanning flow loops characterized by a high-velocity cut-off, respectively. The maximum velocity as a function of the porosity and the overall temperature difference is shown to be indicative for the hydro-thermodynamic Rayleigh-Bénard instability and the geometrical percolation threshold. The coincidence of the Rayleigh-Bénard instability (modified for porous media) and the percolation transition (modified for closed loops) gives rise to a new critical phenomenon termed the Rayleigh-Bénard percolation transition. It occurs at a certain combination of the porosity and the overall temperature difference in the cell. Temperature maps were recorded with the aid of a relaxation-based NMR technique. The consequence of different thermal conductivities in the matrix and in the fluid is that horizontal-temperature gradients arise even in the absence of flow. This leads to a superposition of uncritical convective flow driven by the horizontal-temperature gradients whenever closed-loop pathways are possible and the critical Rayleigh-Bénard convection based on vertical-temperature gradients.

Journal Article↗

Two-dimensional maps at the edge of chaos: numerical results for the Henon map.

The mixing properties (or sensitivity to initial conditions) of the two-dimensional Henon map have been explored numerically at the edge of chaos. Three independent methods, which have been developed and used so far for one-dimensional maps, have been used to accomplish this task. These methods are (i) the measure of the divergence of initially nearby orbits, (ii) analysis of the multifractal spectrum, and (iii) computation of nonextensive entropy increase rates. The results obtained closely agree with those of the one-dimensional cases and constitute a verification of this scenario in two-dimensional maps. This obviously makes the idea of weak chaos even more robust.

Journal Article↗

A comparison of two algorithms for electron-density map improvement by introduction of atomicity: skeletonization, and map sorting followed by refinement.

A comparison has been made of two methods for electron-density map improvement by the introduction of atomicity, namely the iterative skeletonization procedure of the CCP4 program DM [Cowtan & Main (1993). Acta Cryst. D49, 148-157] and the pseudo-atom introduction followed by the refinement protocol in the program suite DEMON/ANGEL [Vellieux, Hunt, Roy & Read (1995). J. Appl. Cryst. 28, 347-351]. Tests carried out using the 3.0 A resolution electron density resulting from iterative 12-fold non-crystallographic symmetry averaging and solvent flattening for the Pseudomonas aeruginosa ornithine transcarbamoylase [Villeret, Tricot, Stalon & Dideberg (1995). Proc. Natl Acad. Sci. USA, 92, 10762-10766] indicate that pseudo-atom introduction followed by refinement performs much better than iterative skeletonization: with the former method, a phase improvement of 15.3 degrees is obtained with respect to the initial density modification phases. With iterative skeletonization a phase degradation of 0.4 degrees is obtained. Consequently, the electron-density maps obtained using pseudo-atom phases or pseudo-atom phases combined with density-modification phases are much easier to interpret. These tests also show that for ornithine transcarbamoylase, where 12-fold non-crystallographic symmetry is present in the P1 crystals, G-function coupling leads to the simultaneous decrease of the conventional R factor and of the free R factor, a phenomenon which is not observed when non-crystallographic symmetry is absent from the crystal. The method is far less effective in such a case, and the results obtained suggest that the map sorting followed by refinement stage should be by-passed to obtain interpretable electron-density distributions.

Algorithms↗

Noncontact mapping of the left ventricle: insights from validation with transmural contact mapping.

It is not clear whether the noncontact electrograms obtained using the EnSite system in the left ventricle resemble most closely endocardial, intramural, or epicardial contact electrograms or a summation of transmural electrograms. This study compared unipolar virtual electrograms from the EnSite system with unipolar contact electrograms from transmural plunge needle electrodes using a 256-channel mapping system. The study also evaluated the effects of differing activation sites (endocardial, intramural, or epicardial). A grid of 50-60 plunge needles was positioned in the left ventricles of eight male sheep. Each needle had four electrodes to record from the endocardium, two intramural sites, and the epicardium. Correlations between contact and noncontact electrograms were calculated on 32,242 electrograms. Noncontact electrograms correlated equally well in morphology and accuracy of timing with endocardial (0.88 +/- 0.15), intramural (0.87 +/- 0.15), epicardial (0.88 +/- 0.15), and transmural summation contact electrograms (0.89 +/- 0.14) during sinus rhythm, endocardial pacing, and epicardial pacing. There was a nonlinear relationship between noncontact electrogram accuracy as measured by correlation with the contact electrogram and distance from the multielectrode array (MEA): beyond 40 mm accuracy decreased rapidly. The accuracy of noncontact electrograms also decreased with increasing distance from the equator of the MEA. Virtual electrograms from noncontact mapping of normal left ventricles probably represent a summation of transmural activation. Noncontact mapping has similar accuracy with either endocardial or epicardial sites of origin of electrical activity provided the MEA is within 40 mm of the recording site.

Animals↗

Structure and function in glaucoma: The relationship between a functional visual field map and an anatomic retinal map.

PURPOSE: To examine the relationship between an anatomic map relating the retinal nerve fiber layer (RNFL) distribution to the optic nerve head and a functional map derived from the interpoint correlation of raw sensitivities in visual field (VF) testing. METHODS: Previously, interpoint correlations were generated for all possible pairs of VF test points in a dataset of 98,821 Humphrey VF test results taken from the Moorfields Eye Hospital archive. The relationship between these correlations and the physical distance between the VF test point pairs was evaluated by Pearson's correlation coefficient and multiple regression analysis. The distance between the pairs of VF test points was calculated in two ways. First, the anatomic map was used to estimate the angular distance at the optic nerve head (ONH), between the RNFL bundles corresponding to the VF test points in each pair (ONHd). Second, the retinal distance between pairs of test points was calculated from the Humphrey VF template (RETd). A best-fit model for predicting functional correlation (FC) from ONHd and RETd was constructed and used to formulate a filter incorporating the anatomic-functional correlation data. RESULTS: All scatterplots showed a negative association between interpoint retinal sensitivity correlation values and distance between points: ONHd (R2 = 0.60) and RETd (R2 = 0.33). The raw sensitivity correlation values could be predicted from a multiple regression model using ONHd, RETd, and a combined interaction of ONHd and RETd (R2 = 0.75, P < 0.00001). The construction of a new filter was based on the equation FC = 0.9325 - (0.0029 . ONHd) - (0.0077 . RETd) + (0.0001 . ONHd . RETd). CONCLUSIONS: A good level of association was observed between the strength of correlation between points in the VF and the relative location of those test points in the peripheral retina and in corresponding RNFL bundles at the ONH. These results help to validate the relationship between structure and function and may be of use in the further refinement of physiologically derived VF filters to reduce measurement noise.

Glaucoma, Open-Angle↗

Catheter ablation of tachycardias after undergoing a surgical atriotomy using a multipolar electrode catheter: conventional mapping method without an electroanatomical mapping system.

BACKGROUND: A variety of supraventricular tachyarrhythmias may occur in patients after undergoing a surgical atriotomy. The purpose of this study was to characterize them and determine the role of conventional mapping. METHODS AND RESULTS: In 45 patients after a surgical atriotomy, 68 atrial tachyarrhythmias were observed. A conventional mapping system with a 20-pole electrode catheter used in the electrophysiological study detected 39 atrial tachycardias (ATs). Type 1 atrial flutter (AFL) was observed in 23 and reverse type 1 AFL in 4. AT was classified into 3 subgroups, namely, incisional macroreentrant AT (n=31), incisional focal AT (n=1) and non-incisional AT (n=7). In the patients with incisional macroreentrant AT after the standard right atriotomy, the 20-pole electrode catheter placed on the incision could easily record the entire sequence of the atrial activation. Successful catheter ablation was achieved in all patients with incisional reentrant AT. The ablation site of incisional reentrant AT was the isthmus between the incision and the superior vena cava cannulation scar in 4, between the incision and the inferior vena cava cannulation scar in 22, and the area at the septal incision in 3. The remaining 2 incisional ATs were left atrial AT and right atrial transincisional AT. CONCLUSIONS: The conventional mapping system is still very useful for making an electrophysiological diagnosis in patients after a standard right atriotomy.

Adult↗

Identifying leaf rust resistance genes and mapping gene Lr37 on the microsatellite map of wheat.

Based on seedling resistance tests, five resistance genes (Lr10, Lr3, Lr13, Lr14a and Lr37) against leaf rust (Puccinia triticina) were identified in 16 cultivars of European winter wheat. STS and SCAR markers were used to verify the presence of the resistance genes Lr37 and Lr10 against leaf rust in cultivars, near-isogenic lines and segregating populations. The Lr37 gene is present in a small translocation from Triticum ventricosum Ces. (Aegilops ventricosa Tausch) and is tightly linked with resistance genes Yr17 and Sr38. The Lr37 gene was identified in the cultivars Kris, Clever, Slade, Apache, Caphorn, Lorraine, Balthasar, Renan and confirmed by two PCR markers. The F3 progenies of the crosses Kris (Lr37) X Nutka (Lr37 not present) were used for map construction. Two STS/SCAR markers specific for Lr37 were mapped in relation to nine polymorphic microsatellites on chromosome 2AS. The microsatellite marker Xgwm1176 mapped relatively close to the STS and SCAR markers for Lr37 with a linkage distance of 4.1 cM.

Base Sequence↗