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At least 1,261 records · Page 70Linked to original sources
PubMed2006

Extraction of phylogenetic network modules from the metabolic network.

BACKGROUND: In bio-systems, genes, proteins and compounds are related to each other, thus forming complex networks. Although each organism has its individual network, some organisms contain common sub-networks based on function. Given a certain sub-network, the distribution of organisms common to it represents the diversity of its function. RESULTS: We extracted such "common" sub-networks, defined as "phylogenetic network modules," using phylogenetic profiles and cluster analysis. The enzymes in the same "phylogenetic network module" have similar phylogenetic profiles and related functions. These modules are shown to be phylogenetic building blocks. Furthermore, the network of the modules illustrated hierarchical feature as well as the network of enzymes involved in the metabolism. CONCLUSION: We conclude that phylogenetic network modules are evolutionary conserved functional units in the metabolic network. We claim that our concept of phylogenetic modules provides a more accurate understanding of the evolution of biological networks.

Animals↗
PubMed1991

In vitro characterization of two types of LDL apheresis module and effect of repetitive LDL apheresis on plasma cholesterol levels and aortic atherosclerosis in heterozygous WHHL rabbits.

In vitro filtration was used to characterize and compare the function of two types of LDL apheresis module: membrane filtration (module M: pore diameter, 0.04 micron; effective surface area, 0.1 m2) and LDL adsorption (module A: a column containing 20 ml of polyvinyl alcohol gels fixed with polyacrylic acid). Module A had better selectivity of LDL removal, while module M could rapidly remove a larger amount of LDL. The effect of repetitive LDL apheresis with module A on the plasma cholesterol level and on the development of aortic atherosclerosis was examined in 6 heterozygous WHHL rabbits (5 to 10 months old; mean plasma total cholesterol level, 270 +/- 39 mg/dl), treated with LDL apheresis at weekly intervals for 2 months. Plasma total and LDL cholesterols were lowered approximately 40% by a signal procedure. The LDL cholesterol level tended to decrease as treatment progressed, while the HDL cholesterol level was unchanged or rose above the baseline value in a week after LDL apheresis. The ratio of atherosclerotic lesion area to whole aortic area was relatively low in treated rabbits (6.5 +/- 1.9%) in comparison with that in 5 untreated heterozygous WHHL rabbits (18.3 +/- 7.7%). The mean cholesterol content in the thoracic aorta was 4.9 +/- 1.3 mg/g wet tissue in treated rabbits vs 13.3 +/- 6.1 mg/g wet tissue in untreated rabbits. These results suggest that repetitive LDL apheresis might be effective in maintaining a lower level of LDL cholesterol and retarding the atherosclerotic process in vivo.

Absorption↗
PubMed2004

Cloning of the Ruminococcus albus cel5D and cel9A genes encoding dockerin module-containing endoglucanases and expression of cel5D in Escherichia coli.

An EcoRI chromosomal DNA fragment of Ruminococcus albus F-40 that conferred endoglucanase activity on Escherichia coli was cloned. An open reading frame (ORF1) and another incomplete reading frame (ORF2) were found in the EcoRI fragment. The ORF2 was completed using inverse PCR genome walking technique. ORF1 and ORF2, which confront each other, encoded cellulases belonging to families 5 and 9 of the glycoside hydrolases and were designated cel5D and cel9A respectively. The cel5D gene encodes 753 amino acids with a deduced molecular weight of 83,409. Cel5D consists of a signal peptide of 24 amino acids, a family-5 catalytic module, a dockerin module, and two family-4 carbohydrate-binding modules (CBMs). The cel9A gene encodes 936 amino acids with a deduced molecular weight of 104,174, consisting of a signal peptide, a family-9 catalytic module, a family-3 CBM, and a dockerin module. The catalytic module polypeptide (rCel5DCat) derived from Cel5D was constructed, expressed, and purified from a recombinant E. coli. The truncated enzyme hydrolyzed cellohexaose, cellopentaose, and cellotetraose to yield mainly cellotriose and cellobiose with glucose as a minor product, but the enzyme was less active toward cellotriose and not active toward cellobiose, suggesting that this enzyme is a typical endoglucanase. rCel5DCat had a Km of 3.9 mg/ml and a Vmax of 37.2 micromol/min/mg for carboxymethycellulose.

Amino Acid Sequence↗
PubMed2003

Amplitude, phase, and hybrid ternary modulation modes of a twisted-nematic liquid-crystal display at approximately 400 nm.

Applicability of a commercial twisted-nematic liquid-crystal display is examined at approximately 400 nm. Different modulation modes predicted by Jones-matrix calculus are experimentally tested. High contrast amplitude modulation with negligible loss, high contrast and low loss hybrid ternary modulation, and 1.5pi continuous phase delay without intensity modulation and with low loss are presented. Simulation results of a 4f holographic system prove the usefulness of the high contrast for amplitude modulation, and the importance of pi phase difference between high transmission white levels in a hybrid ternary modulation.

Journal Article↗
PubMed2004

Large-modulation-depth 2f spectroscopy with diode lasers for rapid temperature and species measurements in gases with blended and broadened spectra.

A method that uses tunable diode lasers is developed for rapid temperature and concentration measurements of gases with highly broadened and congested spectra. Wavelength modulation absorption spectroscopy with 2f detection is utilized, because this derivative method offers benefits in dealing with blended spectral features. The 2f signal depends critically on the modulation depth of the laser alpha, which is increased to values above those typically achieved when wavelength modulation spectroscopy with diode lasers is performed. The 2f method with large modulation depths is validated by using near-IR diode lasers to probe pressure-broadened water-vapor features in the 1.4-microm region over a range of temperatures from 296 to 800 K and at pressures as high as 20 atm. Modulation depths as high as alpha = 0.8 cm(-1) are attained at modulation frequencies of 50 kHz and measurement bandwidths of 15 kHz. Comparisons of experimental results with 2f simulations, based on the HITRAN spectral database, provide confirmation of the capability of this method for rapid measurements of gas temperature and species concentration.

Journal Article↗
PubMed2005

Fiber-based polarization-sensitive Mueller matrix optical coherence tomography with continuous source polarization modulation.

We report on a new configuration of fiber-based polarization-sensitive Mueller matrix optical coherence tomography that permits the acquisition of the round-trip Jones matrix of a biological sample using only one light source and a single depth scan. In this new configuration, a polarization modulator is used in the source arm to continuously modulate the incident polarization state for both the reference and the sample arms. The Jones matrix of the sample can be calculated from the two frequency terms in the two detection channels. The first term is modulated by the carrier frequency, which is determined by the longitudinal scanning mechanism, whereas the other term is modulated by the beat frequency between the carrier frequency and the second harmonic of the modulation frequency of the polarization modulator. One important feature of this system is that, for the first time to our knowledge, the Jones matrix of the sample can be calculated with a single detection channel and a single measurement when diattenuation is negligible. The system was successfully tested by imaging both standard polarization elements and biological samples.

Algorithms↗
PubMed2007

Diffractive optical elements designed for highly precise far-field generation in the presence of artifacts typical for pixelated spatial light modulators.

Diffractive optical elements (DOEs) realized by spatial light modulators (SLMs) often have features that distinguish them from most conventional, static DOEs: strong coupling between phase and amplitude modulation, a modulation versus steering parameter characteristic that may not be precisely known (and may vary with, e.g., temperature), and deadspace effects and interpixel cross talk. For an optimal function of the DOE, e.g. as a multiple-beam splitter, the DOE design must account for these artifacts. We present an iterative design method in which the optimal setting of each SLM pixel is carefully chosen by considering the SLM artifacts and the design targets. For instance, the deadspace-interpixel effects are modeled by dividing the pixel to be optimized, and its nearest neighbors, into a number of subareas, each with its unique response and far-field contribution. Besides the customary intensity control, the design targets can also include phase control of the optical field in one or more of the beams in the beam splitter. We show how this can be used to cancel a strong unwanted zeroth-order beam, which results from using a slightly incorrect modulation characteristic for the SLM, by purposely sending a beam in the same direction but with the opposite phase. All the designs have been implemented on the 256 x 256 central pixels of a reflective liquid crystal on silicon SLM with a selected input polarization state and a direction of transmission axis of the output polarizer such that for the available different pixel settings a phase modulation of ~2pi rad could be obtained, accompanied by an intensity modulation depth as high as >95%.

Journal Article↗
PubMed2001

Phase-map measurements by interferometry with sinusoidal phase modulation and four integrating buckets.

Phase-shifting interferometry based on the integrating-bucket technique with sinusoidal phase modulation is studied theoretically and demonstrated experimentally to obtain phase maps from double-beam interferometers. The method uses four frames obtained by integration of the time-varying intensity in an interference pattern during the four quarters of the modulation period. An optimum sinusoidal phase modulation is found to minimize the effect of the additive noise. The absolute accuracy of the phase measurements is discussed. Possible applications of the method are demonstrated with two interference microscopes with which the phase modulation is achieved by sinusoidal oscillation of a mirror attached to a piezoelectric transducer and by sinusoidal birefringence modulation with a photoelastic modulator. In both experimental arrangements, phase images can be produced in real time at a rate of several hertz. Noise measurements are reported and compared with theory.

Algorithms↗
PubMed2005

Neuronal computation of disparity in V1 limits temporal resolution for detecting disparity modulation.

The human ability to detect modulation of binocular disparity over time is poor compared with detection of luminance modulation. We examined the physiological origin of this limitation by analyzing neuronal responses to temporal modulation of binocular disparity in striate cortex of awake monkeys. When neurons were presented with random-dot stereograms in which disparity varied sinusoidally over time, their responses modulated at the stimulus temporal frequency, with little change in mean firing rate. We calculated modulation amplitude as a function of temporal frequency and compared this with the psychophysical performance of four human observers. Neuronal and psychophysical functions showed similar peak frequencies (2 Hz) and comparable high-cut frequencies (10 and 5.5 Hz, respectively). Thus, V1 (primary visual cortex) neurons appear to limit psychophysical performance. The temporal resolution of the same neurons for contrast modulation was approximately 2.5 times greater, which parallels the superior psychophysical performance for contrast. There is a simple mathematical explanation for this difference: it results from calculating cross-correlation between temporally broadband monocular images that are bandpass filtered before measuring correlation. The limit on temporal resolution is a direct consequence of the binocular energy model that adds to the list of properties of human stereoscopic performance that are explained by this simple model of disparity encoding in V1: the same neurons can account for the performance of psychophysical tasks that result in either high (contrast) or low (disparity) temporal resolution. Because this principle holds whenever a broadband input is bandpass filtered before computing correlation, it may limit the resolution of other neuronal systems.

Animals↗
PubMed2006

Transcranial magnetic stimulation over sensorimotor cortex disrupts anticipatory reflex gain modulation for skilled action.

Skilled interactions with new environments require flexible changes to the transformation from somatosensory signals to motor outputs. Transcortical reflex gains are known to be modulated according to task and environmental dynamics, but the mechanism of this modulation remains unclear. We examined reflex organization in the sensorimotor cortex. Subjects performed point-to-point arm movements into predictable force fields. When a small perturbation was applied just before the arm encountered the force field, reflex responses in the shoulder muscles changed according to the upcoming force field direction, indicating anticipatory reflex gain modulation. However, when a transcranial magnetic stimulation (TMS) was applied before the reflex response to such perturbations so that the silent period caused by TMS overlapped the reflex processing period, this modulation was abolished, while the reflex itself remained. Loss of reflex gain modulation could not be explained by reduced reflex amplitudes nor by peripheral effects of TMS on the muscles themselves. Instead, we suggest that TMS disrupted interneuronal networks in the sensorimotor cortex, which contribute to reflex gain modulation rather than reflex generation. We suggest that these networks normally provide the adaptability of rapid sensorimotor reflex responses by regulating reflex gains according to the current dynamical environment.

Adult↗
PubMedDate not supplied

Significance of schistosomal granuloma modulation.

Hepatic Schistosoma mansoni periovular granulomas undergo changes in size, cellular composition and appearance with time. This phenomenon, known as "immunological modulation", has been thought to reflect host immunological status. However, as modulation has not been observed outside the liver, participation of local factors, hitherto little considered, seems crucial. Components of the extracellular matrix of periovular granulomas of the mouse were particularly studied in three different organs (liver, lung and intestine) and during three periods of infection time (acute, intermediate and chronic) by means of histological, biochemical and immunofluorescence techniques, while quantitative data were evaluated by computerized morphometry, in order to investigate participation of local factors in granuloma modulation. Results confirmed modulation as a exclusively hepatic phenomenon, since pulmonary and intestinal granulomas, formed around mature eggs, did not change size and appearance with time. The matricial components which were investigated (Type I, III and IV collagens, fibronectin, laminin, proteoglycans and elastin) were found in all granulomas and in all organs examined. However, their presence was much more prominent in the liver. Elastin was only found in hepatic granulomas of chronic infection. The large amount of extracellular matrix components found in hepatic granulomas was the main change responsible for the morphological aspects of modulation. Therefore, the peculiar environment of the liver ultimately determines the changes identified in schistosomal granuloma as "modulation".

Animals↗
PubMed2004

Allosteric modulation of G protein-coupled receptors.

G protein-coupled receptors (GPCRs) constitute the largest receptor superfamily in the human genome and represent the most common targets of drug action. Classic agonist and antagonist ligands that act at GPCRs tend to bind to the receptor's orthosteric site, that is, the site recognized by the endogenous agonist for that receptor. However, it is now evident that GPCRs possess additional, extracellular, allosteric binding sites that can be recognized by a variety of small molecule modulator ligands. Allosteric modulators offer many advantages over classic orthosteric ligands as therapeutic agents, including the potential for greater GPCR-subtype selectivity and safety. However, the manifestations of allosterism at GPCRs are many and varied and, in the past, traditional screening methods have generally failed to detect many allosteric modulators. More recently, there have been a number of major advances in high throughput screening, including the advent of cell-based functional assays, which have led to the discovery of more allosteric modulator ligands than previously appreciated. In addition, a number of powerful analytical techniques have also been developed exclusively for detecting and quantifying allosteric effects, based on an increased awareness of various mechanisms underlying allosteric modulator actions at GPCRs. Together, these advances promise to change the current paucity of GPCR allosteric modulators in the clinical setting and yield novel therapeutic entities for the treatment of numerous disorders.

Allosteric Regulation↗
PubMed2005

Discovery of positive allosteric modulators of metabotropic glutamate receptor subtype 5 (mGluR5).

This review provides an overview of the drug discovery process used to identify, develop and characterize the first positive allosteric modulators of the metabotropic glutamate receptor (mGluR) subtype 5 (mGluR5). Discovery and optimization of three series of positive allosteric modulators are described, each using different approaches. The symmetric benzaldazine series was discovered and optimized from samples already existing in our sample collection without an active synthetic program to further elucidate SAR. This series yielded a family of highly selective pharmacological tools that produced positive, negative and neutral allosteric modulation of mGluR5 activity. The original compound in the benzamide series was discovered from screening and this series was optimized using an iterative library synthesis approach to explore SAR in each of three regions of the molecule. This series produced more potent positive allosteric mGluR5 modulators than the benzaldazine series which could be evaluated for their effect on mGluR5 in brain slice electrophysiological studies. The pyrazole series used a fragment library approach based on small structural motives from the benzamide series to discover lead compounds and establish SAR. This series produced still more potent positive allosteric mGluR5 modulators with improved pharmacokinetic and physical properties. These modulators showed efficacy in animal behavioral models in which other antipsychotic drugs were active. Evaluation of assay data in mathematical models of allosterism to constrain possible mechanisms of action is briefly discussed. Other reviews of this emerging field with different emphases have been published recently [1-3].

Allosteric Regulation↗
PubMed2006

Dose reduction and image quality in MDCT colonography using tube current modulation.

OBJECTIVE: The purpose of our study was to evaluate the dose reduction potential of combined online (x- and y-axes) and topogram-based (l) X-ray tube current modulation in CT colonography in a screening population. MATERIALS AND METHODS: Eighty asymptomatic individuals underwent CT colonography screening for colon polyps. A 16-MDCT scanner (Somatom Sensation 16) was used. Forty patients were examined at 120 kVp and 120 effective mAs (supine) and 40 effective mAs (prone) using online x- and y-axis tube current modulation. Another 40 patients were scanned using combined x-, y-, and z-axis tube current modulation. Individual patient radiation exposure was determined using the dose-length product. Image noise was determined by Hounsfield unit measurements in the colonic lumen at four anatomic levels. Image quality was rated on a 5-point confidence scale by two independent reviewers. The unpaired Student's t test (for radiation dose, image noise) and Wilcoxon's test (for image quality) were used to test for statistically significant differences between these values. RESULTS: Radiation dose was significantly lower in the patient group scanned with x-, y-, and z-axis tube current modulation than in the group scanned with x- and y-axis tube current modulation (supine: 4.24 vs 6.50 mSv, p < 0.0001; prone: 1.61 vs 2.38 mSv, p < 0.0001). Radiation dose was reduced by 35% (supine) and 33% (prone). No statistically significant difference was seen in overall image noise (supine: 15.9 vs 16.3 H, p = 0.13; prone: 23.5 vs 24.8 H, p = 0.44) or image quality (supine: 4.6 vs 4.5, p = 0.62; prone: 3.5 vs 3.6, p = 0.54). CONCLUSION: Combined x-, y-, and z-axis tube current modulation leads to a significant reduction of radiation exposure in CT colonography without loss of image quality.

Aged↗
PubMed1994

Effects of aging on amplitude-modulation following response.

Phase spectral analysis as developed by Fridman (1982) was used to detect amplitude-modulation following response (AMFR). The threshold of AMFR was determined with greater sensitivity and accuracy by phase spectral analysis than by visual analysis. Using this method, a modulation frequency (MF) of 80 Hz was found optimal for detecting AMFR in young children (ranging in age from 2 to 4 years) during sleep, for whom there is no advantage in recording 40-Hz steady-state responses. To determine the optimal MF for detecting AMFR during sleep in children less than 2 years of age and age limitation for using 80-Hz MAFR in objective audiometry, AMFR as a function of MF was investigated during sleep in 25 children with normal hearing ranging from 4 months to 15 years of age, and 10 normal hearing adults. The stimulus was a 1000 Hz, 50 dBnHL sinusoidally amplitude modulated tone with a modulation depth of 95%. MF was varied from 20 to 200 Hz in 20 Hz steps. Response was determined by phase spectral analysis and the S/N ratio calculated by spectral amplitude at the modulation frequency and noise level around the modulation frequency using fast Fourier transform. Phase spectral analysis showed AMFR at MF of 80 Hz to be the most stable and reliable in all children during sleep among MFs from 20 to 200 Hz. Spectral amplitude analysis demonstrated 80-Hz AMFR to have a high S/N ratio in all children.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMedDate not supplied

Terminology support for development of sharable knowledge modules.

Lack of an agreed infrastructure for terminology is identified as one of the major barriers to interchange of knowledge modules and integration of knowledge bases with other clinical information systems. The goal of the GALEN project is to bridge this gap between different terminology systems through the construction of a terminology server, which is based on a rich conceptual model with mapping facilities to natural language expressions and coding schemas. The long term goal is to support communication between medical information systems. Arden Syntax is a standard format for the creation of knowledge modules, with sharability as one of the main objectives. Since Arden Syntax is based on a data-driven approach, the data items used need to be adapted to locally available terminology. The GALEN approach appears to be complementary to Arden Syntax and to the development of sharable knowledge modules. The major theme of this paper is utilization of the GALEN terminology server for knowledge module authoring. Two systems are presented, a knowledge base manager and a client to the terminology server, allowing the user to navigate in the semantic network and to import concept definitions and terms into the knowledge modules. The benefit of the terminology server, allowing the user to navigate in the semantic network and to import concept definitions and terms into the knowledge modules. The benefit of the terminology services is discussed.

Artificial Intelligence↗
PubMed1990

Modulation of gene expression in autoimmune disease and aging by food restriction and dietary lipids.

Several recent observations carried out by many investigators have offered some clues in understanding the mechanism of how food restriction (FR) acts in the prolongation of life-span, but the precise mechanisms involved in modulating the immune system have not been clearly understood. Our own ongoing studies indicate that FR may act at the molecular level and may extend the life-span by modulating functional activities of several genes in various target tissues. For instance, while cytochrome P-450 IIB1 and IIB2 expression is known to decline with age in ad libitum-fed rats, FR prevented the loss of (drug-inducible) P-450 enzymes in liver tissues. In addition, both alpha 2u-globulin and senescence marker protein 2 expressions, which are regulated by hormones, were also modulated during aging by FR in Fischer 344 male rats. In short-lived autoimmune-prone mice, both FR and omega-3 (n-3) fatty acids diet lowered the severity of autoimmune disease both in lupus-prone (NZB x NZW)F1 mice and in mice prone to develop lymphoproliferative and renal diseases, whereas saturated (n-9) and polyunsaturated (n-6) dietary lipids not only exacerbated autoimmune disease, but also significantly enhanced expression of several oncogenes in lymphoid tissues. FR and omega-3 fatty acids decreased the expression of certain oncogenes. Both FR and omega-3 fatty acids may modulate the aging and autoimmune disease processes by not only altering the fatty acid composition, membrane fluidity, and signal transduction, but also by modulating the lymphokine hormone receptors and their functions and thereby modulating expression of several genes in various tissues during the aging process.

Aging↗
PubMed1996

Use of speech-modulated noise adds strong "bottom-up" cues for phonemic restoration.

When deleted segments of speech are replaced by extraneous sounds rather than silence, the missing speech fragments may be perceptually restored and intelligibility improved. This phonemic restoration (PhR) effect has been used to measure various aspects of speech processing, with deleted portions of speech typically being replaced by stochastic noise. However, several recent studies of PhR have used speech-modulated noise, which may provide amplitude-envelope cues concerning the replaced speech. The present study compared the effects upon intelligibility of replacing regularly spaced portions of speech with stochastic (white) noise versus speech-modulated noise. In Experiment 1, filling periodic gaps in sentences with noise modulated by the amplitude envelope of the deleted speech fragments produced twice the intelligibility increase obtained with interpolated stochastic noise. Moreover, when lists of isolated monosyllables were interrupted in Experiment 2, interpolation of speech-modulated noise increased intelligibility whereas stochastic noise reduced intelligibility. The augmentation of PhR produced by modulated noise appeared without practice, suggesting that speech processing normally involves not only a narrowband analysis of spectral information but also a wideband integration of amplitude levels across critical bands. This is of considerable theoretical interest, but it also suggests that since PhRs produced by speech-modulated noise utilize potent bottom-up cues provided by the noise, they differ from the PhRs produced by extraneous sounds, such as coughs and stochastic noise.

Attention↗