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At least 163 records · Page 9Linked to original sources

PubMed2003

Wavelength modulation spectroscopy: combined frequency and intensity laser modulation.

A theoretical model of wavelength modulation spectroscopy that uses a laser diode on a Lorentzian absorption line is presented. This theory describes the general case of a current-modulated semiconductor laser, for which a combined intensity and frequency modulation with an arbitrary phase shift occurs. On the basis of this model, the effect of several modulation parameters on the detected signals is evaluated. Experimental signals measured on an absorption line of CO2 by use of a 2-microm distributed-feedback laser are also presented and validate this analysis. These experimental results agree with the calculated signals, confirming the relevance of the model.

Journal Article↗

PubMed2005

Optical rotatory-dispersion-type spatial light modulator and characteristics of the modulated light.

Among known temporal-spatial light modulation methods, there is no realistic method that can precisely control a light pulse simultaneously in the temporal and spatial domains. By careful consideration of the symmetries and topological properties of electromagnetic waves, a novel spatial light modulator has been developed to create different far-field patterns for each wavelength of linearly polarized light composed of various wavelength components. The system consists of an optical rotatory dispersion device, which is like a Faraday rotator, and a spatial light modulator with parallel-alignment nematic liquid-crystal cells. Numerical simulation results show the effectiveness of this new spatial light modulation method.

Journal Article↗

PubMed2006

Diffraction-based determination of the phase modulation for general spatial light modulators.

We describe a characterization method based on diffraction for obtaining the phase response of spatial light modulators (SLMs), which in general exhibit both amplitude and phase modulation. Compared with the conventional interferometer-based approach, the method is characterized by a simple setup that enables in situ measurements, allows for substantial mechanical vibration, and permits the use of a light source with a fairly low temporal coherence. The phase determination is possible even for a SLM with a full amplitude modulation depth, i.e., even if there are nulls in the amplitude transmission characteristic of the SLM. The method successfully determines phase modulation values in the full 2pi rad range with high accuracy. The experimental work includes comparisons with interferometer measurements as well as a SLM characterization with a light-emitting diode (LED).

Journal Article↗

PubMed2001

Modulation of P-glycoprotein (PGP) mediated multidrug resistance (MDR) using chemosensitizers: recent advances in the design of selective MDR modulators.

Over the past two decades, a number of chemical entities have been investigated in the continuing quest to reverse P-glycoprotein (PGP) mediated multidrug resistance (MDR) in cancer. The complexity of interactions between these agents and the proteins responsible for MDR in conjunction with the challenges associated with developing SAR/QSAR relationships for MDR modulators has hampered our ability to develop agents that modulate MDR with enhanced specificity of target, increased efficacy, and minimized toxicity when coadministered with anticancer drugs. With an increased understanding of the molecular interaction, target-mediated SAR and combinatorial chemistry approaches, newer more selective inhibitors have been recently reported. These agents have shown remarkable promise in preclinical trials; although their ultimate clinical therapeutic utility remains to be established. The emphasis of this review is placed on the current understanding of modulator-drug transport protein interactions and to review the advances in the structure-based design, synthetic efforts and the cellular pharmacology of MDR modulating activity of a number of known PGP inhibitors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Modulation of neonatal microbial recognition: TLR-mediated innate immune responses are specifically and differentially modulated by human milk.

The mechanisms controlling innate microbial recognition in the neonatal gut are still to be fully understood. We have sought specific regulatory mechanisms operating in human breast milk relating to TLR-mediated microbial recognition. In this study, we report a specific and differential modulatory effect of early samples (days 1-5) of breast milk on ligand-induced cell stimulation via TLRs. Although a negative modulation was exerted on TLR2 and TLR3-mediated responses, those via TLR4 and TLR5 were enhanced. This effect was observed in human adult and fetal intestinal epithelial cell lines, monocytes, dendritic cells, and PBMC as well as neonatal blood. In the latter case, milk compensated for the low capacity of neonatal plasma to support responses to LPS. Cell stimulation via the IL-1R or TNFR was not modulated by milk. This, together with the differential effect on TLR activation, suggested that the primary effect of milk is exerted upstream of signaling proximal to TLR ligand recognition. The analysis of TLR4-mediated gene expression, used as a model system, showed that milk modulated TLR-related genes differently, including those coding for signal intermediates and regulators. A proteinaceous milk component of > or =80 kDa was found to be responsible for the effect on TLR4. Notably, infant milk formulations did not reproduce the modulatory activity of breast milk. Together, these findings reveal an unrecognized function of human milk, namely, its capacity to influence neonatal microbial recognition by modulating TLR-mediated responses specifically and differentially. This in turn suggests the existence of novel mechanisms regulating TLR activation.

Cell Line↗

PubMedDate not supplied

[Model analysis of the effect of modulated electromagnetic fields with various parameters of modulating signals in cells].

A theoretical analysis of the dependence of cell response to modulated electromagnetic fields on the parameters of modulating signals was performed on the basis of the model for calcium-dependent membrane-associated intracellular signaling systems. Expressed amplitude-frequency "windows" in the response of the nonlinear system to external influence were shown to depend on the effective time during which the amplitude of the influencing signal exceeded some threshold value, which is determined by the properties of the system. The presence of negative values in the influencing signal, i.e. the variations in the rate of some process around the inherent value, played an important role for the effect characteristics. The response of the nonlinear system to external influence strongly depended on the waveform of the modulating signal which is determined not only by frequency spectrum, but also by the initial phase of each frequency component. To ensure a regime for the optimal effect, the rates of increase and drop in the modulating signal amplitude should be synchronized with dynamic processes in the biological object being exposed.

Algorithms↗

PubMed1991

Quantitative characterization of the intrinsic ligand-binding affinity of the interleukin 2 receptor beta chain and its modulation by the alpha chain and a second affinity-modulating element.

The interleukin 2 receptor is a multisubunit receptor known to consist of at least two IL-2 binding subunits, alpha and beta. We report here kinetic evidence defining the contribution of an affinity-modulating element(s) intimately involved in modulation of the ligand-binding affinity of the beta chain and alpha/beta complex. The principal effect of this modulating element on the beta chain is to slow the dissociation of IL-2 more than 150-fold and thus raise its low intrinsic IL-2 binding affinity (Kd = 70 nM) as defined in transfected fibroblast cells to the level observed in lymphoid cells (Kd = 1.2 nM). The alpha subunit also increases the ligand-binding affinity of the beta chain, although in this case principally by increasing the association rate constant more than 1200-fold. The additional effect of the affinity-modulating element on the alpha/beta complex is minimal with regards to the equilibrium binding affinity. It does, however, have a detectable 14-fold effect on slowing the IL-2 dissociation rate. The existence of multiple forms of IL-2 receptor complexes with widely varying ligand affinities and dissociation rates illustrates the need for careful evaluation of binding data in studies of receptor subunit composition and reconstitution.

Animals↗

PubMedDate not supplied

[The characteristics of the latent periods of movements in cats during the differentiation of tonal and amplitude-modulated signals with changes in the modulation from high frequencies to low].

The latent periods of the forepaw movements of cats were studied in the course of differentiation task performance. Pure tones and amplitude-modulated stimuli had to be differentiated. It was found out that the mean latency of motor responses to pure tones was significantly higher than that of responses to modulated signals. The latencies to the applied stimuli did not differ in the simple task (without differentiation). The latencies were influenced not only by the absolute values of modulation frequency but also by the frequency shift in successive experiments. Lowering modulation frequency decreased the latency. This effect was especially expressed around the values of 205-207 and 33-34 Hz.

Acoustic Stimulation↗

PubMedDate not supplied

Calcium signaling and synaptic modulation: regulation of endocannabinoid-mediated synaptic modulation by calcium.

Postsynaptic Ca2+ signal influences synaptic transmission through multiple mechanisms. Some of them involve retrograde messengers that are released from postsynaptic neurons in a Ca2+-dependent manner and modulate transmitter release through activation of presynaptic receptors. Recent studies have revealed essential roles of endocannabinoids in retrograde modulation of synaptic transmission. Endocannabinoid release is induced by either postsynaptic Ca2+ elevation alone or activation of postsynaptic Gq/11-coupled receptors with or without Ca2+ elevation. The former pathway is independent of phospholipase Cbeta (PLCbeta) and requires a large Ca2+ elevation to a micromolar range. The latter pathway requires PLCbeta and is facilitated by a moderate Ca2+ elevation to a submicromolar range. This facilitation is caused by Ca2+-dependency of receptor-driven PLCbeta activation. The released endocannabinoids then activate presynaptic cannabinoid receptor type 1 (CB1), and suppress transmitter release from presynaptic terminals. Both CB1 receptors and Gq/11-coupled receptors are widely distributed in the brain. Thus, the endocannabinoid-mediated retrograde modulation may be an important and widespread mechanism in the brain, by which postsynaptic events including Gq/11-coupled receptor activation and Ca2+ elevation can retrogradely influence presynaptic function.

Animals↗

PubMed1997

Opioid modulation of attention-related responses: delta-receptors modulate habituation and conditioned bradycardia.

Endogenous opioids modulate attention-related heart rate responses evoked by novel stimuli and conditioned signals in ways that differ from their better-known effects on motivation and memory functions. We investigated the role of delta-opioids in modulating bradycardiac orienting and Pavlovian conditioned responses in rabbits, following i.v. treatment with the highly selective delta-receptor antagonist naltrindole (NTI; 0.037-0.370 mg/kg). When administered immediately before testing, NTI induced modest but detectable effects: the lowest dose increased cardiac discrimination near the end of the first training session, whereas the higher doses of NTI impaired discrimination, compared to saline-treated controls. NTI treatment immediately before testing also appeared to promote habituation of bradycardiac orienting responses elicited by novel tones, but NTI did not alter unconditioned heart rate responses following tone-shock pairs or extinction of conditioned responses. In contrast, the low dose of NTI administered 20 min, rather than immediately before testing, facilitated conditioned bradycardia during extinction, as well as during training. These results provide evidence that endogenous delta-opioid modulators normally delay the disappearance of bradycardiac orienting responses during habituation, inhibit or promote the development of bradycardiac conditioned responses during Pavlovian training depending on dose, and promote the disappearance of conditioned responses during extinction. These findings suggest that endogenous delta-opioid activity, probably involving both peripheral and central systems, coincides with, and may reflect, uncertainty about stimulus significance.

Animals↗

PubMed2000

Differential modulation of chemosensitivity to alkylating agents and platinum compounds by DNA repair modulators in human lung cancer cell lines.

PURPOSE: Modulation of DNA repair represents one strategy to overcome cellular drug resistance to alkylating agents and platinum compounds. The effects of different known DNA repair modulators such as O6-benzylguanine (6 microg/ml), fludarabine (25 ng/ml), aphidicolin (8.5 ng/ml), pentoxifylline (1.4 microg/ml) and methoxamine (12.4 microg/ml) on the cytotoxicity of mafosfamide, chlorambucil, 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), cisplatin and carboplatin were tested in human lung cancer cell lines. METHODS: Chemosensitivity of the human adenocarcinoma cell line MOR/P and the cisplatin-resistant subline MOR/CPR as well as the large-cell lung cancer cell line L23/P and its cisplatin-resistant counterpart L23/CPR were evaluated by the MTT colorimetric assay. RESULTS: O6-benzylguanine, an inhibitor of O6-alkylguanine-DNA alkyltransferase, significantly sensitised MOR/P and MOR/CPR cells to the cytotoxic effect of BCNU. Fludarabine, methoxamine and aphidicolin did not change the chemosensitivity of the parental and cisplatin-resistant cell lines to any cytotoxic drug tested. Interestingly, O6-benzylguanine enhanced the chemoresistance of parental and cisplatin-resistant cell lines to platinum compounds. Also, pentoxifylline increased resistance of the MOR cell lines to mafosfamide. CONCLUSIONS: Modulation of DNA repair elicits not only chemosensitisation but may also enhance cellular resistance to DNA-affine drugs.

Antineoplastic Agents, Alkylating↗

PubMed1984

The sensitivity of the peripheral visual system to amplitude-modulation and frequency-modulation of sine-wave patterns.

The detectability of amplitude modulation and spatial frequency modulation of suprathreshold sine-wave gratings was measured at retinal eccentricities ranging from 0 to 30 deg. The main conclusions to be drawn from the experimental results are: (1) for this visual task it is not possible to bring peripheral sensitivity to the same level as foveal sensitivity by scaling the stimuli with the inverse of the cortical magnification factor M. (2) Increasing the number of cycles in the carrier grating improves modulation detectability. For gratings in the periphery this holds up to the largest stimulus size used (64 cycles). In earlier investigations it has been shown that for central vision the improvement ends at about 16 cycles.

Form Perception↗

PubMed2004

Dose conformation of intensity-modulated stereotactic photon beams, proton beams, and intensity-modulated proton beams for intracranial lesions.

PURPOSE: This study evaluates photon beam intensity-modulated stereotactic radiotherapy (IMSRT) based on dynamic leaf motion of a micromultileaf collimator (mMLC), proton beams, and intensity-modulated proton therapy (IMPT) with respect to target coverage and organs at risk. METHODS AND MATERIALS: Dose plans of 6 stereotactically treated patients were recalculated for IMSRT by use of the same field setup and an inverse planning algorithm. Proton and IMPT plans were calculated anew. Three different tumor shapes, multifocal, ovoid, and irregular, were analyzed, as well as dose to organs-at-risk (OAR) in the vicinity of the planning target volume (PTV). Dose distributions were calculated from beam-setup data for a manual mMLC for stereotactically guided conformal radiotherapy (SCRT), a dynamic mMLC for IMSRT, the spot-scanning technique for protons, and a modified spot-scanning technique for IMPT. SCRT was included for a part of the comparison. Criteria for assessment were PTV coverage, dose-volume histograms (DVH), volumes of specific isodoses, and the dose to OAR. RESULTS: Dose conformation to the PTV is equally good for all three techniques and tumor shapes considered. The volumes of the 90% and 80% isodose were comparable for all techniques. For the 50% isodose volume, a divergence between the two modes was seen. In 3 cases, this volume is smaller for IMSRT, and in the 3 other cases, it is smaller for IMPT. This difference was even more pronounced for the volumes of the 30% isodose; IMPT shows further improvement over conventional protons. OAR in concavities (e.g., the brainstem) were similarly well spared by protons and IMSRT. IMPT spares critical organs best. Fewer proton beams are required to achieve similar results. CONCLUSIONS: The addition of intensity modulation improves the conformality of mMLC-based SCRT. Conformation of dose to the PTV is comparable for IMSRT, protons, and IMPT. Concerning the sparing of OAR, IMSRT is equivalent to IMPT, and IMPT is superior to conventional protons. The advantage of protons lies in the lower integral dose.

Algorithms↗

PubMed2005

Extracellular inosine modulates ERK 1/2 and p38 phosphorylation in cultured Sertoli cells: possible participation in TNF-alpha modulation of ERK 1/2.

Extracellular ATP and adenosine modulation of MAPKs is well described in different cells types, but few studies have addressed the effects of extracellular inosine on these kinases. Previous results showed that hydrogen peroxide and TNF-alpha increase extracellular inosine concentration in cultured Sertoli cells and this nucleoside protects Sertoli cells against hydrogen peroxide induced damage and participates in TNF-alpha induced nitric oxide production. In view of the fact that MAPKs are key mediators of the cellular response to a large variety of stimuli, we investigated the effect of extracellular inosine on the phosphorylation of ERK 1/2 and p38 MAPKs in cultured Sertoli cells. The involvement of this nucleoside in the activation of ERK 1/2 by TNF-alpha was also investigated. Inosine and the selective A1 adenosine receptor agonist R-PIA increases the phosphorylation of ERK 1/2 and p38, and this was blocked by the selective A1 adenosine receptors antagonists, CPT and DPCPX. These antagonists also inhibited TNF-alpha increase in the phosphorylation of ERK 1/2. TNF-alpha also rapidly augmented extracellular inosine concentration in cultured Sertoli cells. These results show that extracellular inosine modulates ERK 1/2 and p38 in cultured Sertoli cells, possible trough A1 adenosine receptor activation. This nucleoside also participates in TNF-alpha modulation of ERK 1/2.

Animals↗

PubMed2006

To modulate or not to modulate: differing results in uniquely shaped Williams syndrome brains.

Voxel based morphometry (VBM) studies of Williams syndrome (WS) have demonstrated remarkably consistent findings of reduced posterior parietal gray matter compared to typical controls. Other WS VBM findings have been inconsistent, however. In particular, different findings have been reported for hypothalamus and orbitofrontal gray matter regions. We examined a sample of 8 WS and 9 control adults and show that the hypothalamus and orbitofrontal cortex results depend on whether the images undergo Jacobian modulation. Deformation based morphometry (DBM) analysis demonstrated that major brain shape differences between the groups accounted for the Jacobian modulated gray matter findings. These results indicate that cautious interpretations of modulated gray matter findings are warranted when there are gross shape and size differences between experimental groups. This study demonstrates the importance of methodological choices towards understanding a disorder like WS, but also highlights the consistency of parietal lobe, orbitofrontal, and midbrain findings for this disorder across methodologies, participants, and research groups.

Adult↗

PubMed2002

Orientation- and frequency-modulated textures at low depths of modulation are processed by off-orientation and off-frequency texture mechanisms.

Intuitively it may seem likely that orientation-modulated (OM) and frequency-modulated (FM) textures are processed utilizing the first-order channels that are most responsive to the first-order (luminance) information contained in the textures. This assumption would imply that the detection or segmentation of OM or FM textures is accomplished by second-order mechanisms that receive their first-order input from neurons tuned to either the center, or to the peaks in the orientation and spatial-frequency distribution of the texture. Here we show that at low depths of modulation this is not the case. Using an adaptation paradigm, we show that the first-order filters involved in the perception of OM and FM textures are those which maximize the differential response between the different texture regions. Our explanation of this result is similar to that made by Regan and Beverley [J. Opt. Soc. Am. 73 (1983) 1684; J. Opt. Soc. Am. A 2 (1985) 147] for simple grating stimuli. However, we show that whereas Regan and Beverley's results could be accounted for on the basis of the tuning functions of the putative mechanisms involved, our results can be explained in terms of the characteristics of the textures themselves. Some implications of our finding are discussed.

Adaptation, Ocular↗

PubMed2003

Retrieving modulation parameters from HRTEM images of modulated structures.

Quantitative high-resolution transmission electron microscopy (qHRTEM) is methodologically extended towards the assessment of occupationally and positionally modulated structures. For this purpose, iterative digital image matching has been combined with data processing within the Rietveld refinement code JANA2000. In this approach, the number of free parameters is kept low and rather complicated modulated structures become assessable by qHRTEM. The feasibility of the improved methodology is demonstrated for the 1D modulated structure of Ba(2)TiGe(2)O(8).

Journal Article↗

PubMed2000

Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs.

In recent years, there has been an increased understanding of P-glycoprotein (P-GP)-mediated pharmacokinetic interactions. In addition, its role in modifying the bioavailability of orally administered drugs via induction or inhibition has been also been demonstrated in various studies. This overview presents a background on some of the commonly documented mechanisms of multidrug resistance (MDR), reversal using modulators of MDR, followed by a discussion on the functional aspects of P-GP in the context of the pharmacokinetic interactions when multiple agents are coadministered. While adverse pharmacokinetic interactions have been documented with first and second generation MDR modulators, certain newer agents of the third generation class of compounds have been less susceptible in eliciting pharmacokinetic interactions. Although the review focuses on P-GP and the pharmacology of MDR reversal using MDR modulators, relevance of these drug transport proteins in the context of pharmacokinetic implications (drug absorption, distribution, clearance, and interactions) will also be discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗