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At least 1,333 records · Page 74Linked to original sources
PubMed2000

Enhanced cerebral uptake of receptor ligands by modulation of P-glycoprotein function in the blood-brain barrier.

Low cerebral uptake of some therapeutic drugs can be enhanced by modulation of P-glycoprotein (P-gp), an ATP-driven drug efflux pump at the blood-brain barrier (BBB). We investigated the possibility of increasing cerebral uptake of the beta-adrenergic ligands S-1'-[(18)F]-fluorocarazolol (FCAR) and [(11)C]-carazolol (CAR) in P-gp knockout mice (mdr1a (-/-)) and by modulation of P-gp with cyclosporin A (CsA) in rats. Specific and nonspecific binding of FCAR in the rat brain were doubled by CsA, while target/nontarget ratios and clearance from plasma (area under curve (AUC)) were not affected. Cerebral uptake of CAR in rats was much lower than FCAR and nonspecific. CsA increased this uptake 5-6-fold, not only due to P-gp modulation in the BBB but also to a 2-fold higher plasma AUC. In the CNS of mdr1a (-/-) mice, uptake of FCAR and CAR was, respectively, 2-fold and 3-fold higher than in mdr1a (+/+) mice. These results indicate that the cerebral uptake of beta-adrenoceptor ligands can be increased by administration of P-gp modulators such as CsA without affecting regional distribution in the brain. P-gp modulation could improve the count statistics in PET studies of the CNS.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1999

Modulation of surface transferrin receptors in lymphoid cells de novo infected with human immunodeficiency virus type-1.

To investigate whether transferrin receptor (CD71) expression is affected by acute HIV-1 infection, three different lymphoid cell lines (MT-4, SUPT-1, H9) were infected with HIV-1 and tested for surface CD71 expression after different incubation periods depending on cell survival after infection. We found that expression of surface CD71 was lower in cells infected with HIV-1 than in uninfected controls: the timing and extent of this down-modulation depended apparently on the different susceptibility of the cell lines to HIV-1 infection and cytopathogenicity. Citrate, a molecule capable of chelating iron, dose-dependently prevented down-modulation of surface CD71 in HIV-1 infected cells as well as viral cytopathic effects. We conclude that (i) expression of surface transferrin receptors is down-modulated by acute HIV-1 infection in T lymphoid cells, that (ii) this cell phenotypic modulation is associated with the cytopathic effects of the virus, and that (iii) these phenomena are modulated by iron chelation. These results support the view that iron metabolism may be an important area for interaction between HIV-1 and human cells.

ADP-ribosyl Cyclase↗
PubMed2000

Vasotocin innervation and modulation of vocal-acoustic circuitry in the teleost Porichthys notatus.

Arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin (AVP) modulate reproduction-related and other social behaviors in a broad range of vertebrate species. These functions of AVT/AVP may be in part achieved through the modulation of sensorimotor integration, although experimental evidence supporting this hypothesis remains limited. In the present experiments, we demonstrate (1) AVT innervation of candidate vocal-acoustic brain regions, and (2) AVT modulation of vocal-motor physiology in the plainfin midshipman fish (Porichthys notatus), which uses vocalizations in both mate attraction and agonistic contexts. AVT distribution was compared with known vocally active brain regions and to central auditory and vocal pathways. AVT-immunoreactive fibers and putative terminals descend almost exclusively from the preoptic area and are found in two primary candidate sites for vocal-acoustic integration - the anterior tuberal hypothalamus and paralemniscal midbrain tegmentum. AVT immunoreactivity is also located in several other vocally active regions, including the ventral tuberal nucleus, periaqueductal gray, and paraventricular regions of the isthmus and rostral hindbrain. The parvocellular preoptic area itself is also vocally active, although thresholds are substantially higher than for other regions. The functional significance of AVT input to vocal-acoustic regions was demonstrated in the paralemniscal midbrain where local delivery of AVT modulated electrically evoked, rhythmic vocal-motor output, which precisely mimicked natural vocalizations. AVT produced dose-dependent inhibitions of parameters associated with call initiation (burst latency and number of vocal-motor bursts elicited) but not of vocal-motor patterning (fundamental frequency and burst duration). Together, these findings provide support for the proposal that AVT modulates sensorimotor processes underlying social/acoustic communication.

Animals↗
PubMed1980

The intervention of a modulator with learning disabled children.

Tested the role of a child modulator, an investigator, and coordinator of services for learning disabled children. Ninety regular third- and fourth- grade children with average intelligence were selected from a population of 1,030 children on the basis of low scores on the Pupil Rating Scale and at least one of four Metropolitan Achievement subtests and were assigned randomly to one of three groups. The first group received the services of the modulator for a 6-month period, while the respective schools were informed of the teachers' ratings and achievement test scores for the second group, and the third group was an untreated control. In addition to the selection procedures, school grades, the Piers-Harris Self-Concept Scale and the Connors Parents Questionnaire were completed before and after treatment. The results showed teacher ratings and achievement score changes for all groups with the modulation group superior only in teacher ratings of Personal-Social behavior. Follow-up testing 18 months later between the modulated and school informed group within the Piers-Harris Scale and ratings by unbiased teachers reflected numerous differences, which suggests a growing self-confidence in the modulated Ss. The positive usefulness of this form of intervention in meeting the general needs of the child and in treating the concomitants of school failure are discussed.

Canada↗
PubMed1983

Suppression of T-lymphocyte cytotoxicity following exposure to sinusoidally amplitude-modulated fields.

Significant inhibition of allogeneic cytotoxicity of the target cell MPC-11 by the murine cytotoxic T-lymphocyte line CTLL-1 was observed when the 4-h cytotoxicity assay was conducted in the presence of a 450-MHz field sinusoidally amplitude-modulated at 60 Hz. Exposure of the effector cells to the field prior to adding them to the target cells in the cytolytic assay resulted in a similar inhibition, suggesting a direct interaction of the field with the cytolytic T lymphocyte. The inhibition was preferentially expressed during the early allogeneic recognition phase. Field-exposed cytolytic cells recovered their full cytolytic capacity in 12.5 h. A differential susceptibility was observed with modulation frequencies from 0 to 100 Hz. Peak suppression occurred at 60 Hz modulation, with progressively smaller effects at 40, 16, and 3 Hz. The unmodulated carrier wave did not affect the cytotoxicity. Effects with 80- and 100-Hz modulation were smaller than at 60 Hz. These results demonstrate an inhibitory but recoverable effect by certain amplitude modulations of weak nonionizing radiation upon the cell-mediated cytolytic immune response.

Animals↗
PubMed2000

Adenosine modulates cell growth in baby hamster kidney (BHK) cells.

Adenosine is known to modulate cell growth in a variety of mammalian cells either via the activation of receptors or through metabolism. We investigated the effect of adenosine on Baby Hamster Kidney (BHK) cell growth and attempted to determine its mechanism of modulation. In wild-type BHK cells, adenosine evoked a biphasic response in which a low concentration of adenosine (1-5 microM) produced an inhibition of colony formation but at higher concentrations (up to 50 microM) this inhibition was progressively reversed. However, no biphasic response was observed in an "adenosine kinase" deficient BHK mutant, "5a", which suggests that adenosine kinase plays an important role in the modulation of growth response to adenosine. Adenosine receptors did not appear to have a role in regulating cell growth of BHK cells. Specific A1 and A2 receptor antagonists were unable to reverse the effect of adenosine on cell growth. Even though a specific A3 adenosine receptor antagonist MRS-1220 partly reversed the inhibition in colony formation at 1 microM adenosine, it also affected the transport of adenosine. Thus adenosine transport and metabolism appears to play the major role in this modulation of cell growth as 5'-amino-5'-deoxyadenosine, an adenosine kinase inhibitor, reversed the inhibition of cell growth observed at 1 microM adenosine. These results, taken together, would suggest that adenosine modulates cell growth in BHK mainly through its transport and metabolism to adenine nucleotides.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed2004

Resistance to signal activation governs design features of the MAP kinase signaling module.

Given its broad influence over numerous cell functions, redesigning the mitogen-activated protein (MAP) kinase signaling module would offer a powerful means to engineer cell behavior. Early challenges include identifying quantitative module features most relevant to biological function and developing simple design rules to predictably modify these features. This computational study delineates how features such as signal amplification, input potency, and dynamic range of output may be tuned by manipulating chief module components. Importantly, the model construction identifies a metric of resistance to signal activation that quantitatively predicts module features and design trade-offs for broad perturbations in kinase and phosphatase expression. Its predictive utility extends to dynamic properties such as signal lifetime, which often dictates MAP kinase effect on cell function. Taken together, we propose that predictably altering MAP kinase signaling by tuning resistance is not only a feasible engineering strategy, but also one exploited by natural systems to allow each MAP kinase to exert pleiotropic effects in a context-dependent manner. External stimuli not only activate kinases, but also alter phosphatase expression and activity, thereby reconfiguring a single module for quantitatively distinct modes of signaling such as transient vs. sustained dynamics, each with unique effects on cell function.

Computer Simulation↗
PubMed2005

An enzyme module system for the synthesis of dTDP-activated deoxysugars from dTMP and sucrose.

A flexible enzyme module system is presented that allows preparative access to important dTDP-activated deoxyhexoses from dTMP and sucrose. The strategic combination of the recombinant enzymes dTMP-kinase and sucrose synthase (SuSy), and the enzymes RmlB (4,6-dehydratase), RmlC (3,5-epimerase) and RmlD (4-ketoreductase) from the biosynthetic pathway of dTDP-beta-L-rhamnose was optimized. The SuSy module (dTMP-kinase, SuSy, +/-RmlB) yielded the precursor dTDP-alpha-D-glucose (2) or the biosynthetic intermediate dTDP-6-deoxy-4-keto-alpha-D-glucose (3) on a 0.2-0.6 g scale with overall yields of 62 % and 72 %, respectively. A two-step strategy in which the SuSy module was followed by the deoxysugar module (RmlC and RmlD) resulted in the synthesis of dTDP-beta-L-rhamnose (4; 24.1 micromol, overall yield: 35.9 %). Substitution of RmlC by DnmU from the dTDP-beta-L-daunosamine pathway of Streptomyces peucetius in this module demonstrated that DnmU acts in vitro as a 3,5-epimerase with 3 as substrate to yield 4 (32.2 mumol, overall yield: 44.7 %). Chemical reduction of 3 with NaBH4 gave a mixture of the C-4 epimers dTDP-alpha-D-quinovose (6) and dTDP-alpha-D-fucose (7) in a ratio of 2:1. In summary, the modular character of the presented enzyme system provides valuable compounds for the biochemical characterization of deoxysugar pathways playing a major role in microbial producers of antibiotic and antitumour agents.

Base Sequence↗
PubMed2002

The PedsQL in pediatric cancer: reliability and validity of the Pediatric Quality of Life Inventory Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module.

BACKGROUND: The Pediatric Quality of Life Inventory (PedsQL) is a modular instrument designed to measure health-related quality of life (HRQOL) in children and adolescents ages 2-18 years. The PedsQL 4.0 Generic Core Scales are multidimensional child self-report and parent proxy-report scales developed as the generic core measure to be integrated with the PedsQL disease specific modules. The PedsQL Multidimensional Fatigue Scale was designed to measure fatigue in pediatric patients. The PedsQL 3.0 Cancer Module was designed to measure pediatric cancer specific HRQOL. METHODS: The PedsQL Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module were administered to 339 families (220 child self-reports; 337 parent proxy-reports). RESULTS: Internal consistency reliability for the PedsQL Generic Core Total Scale Score (alpha = 0.88 child, 0.93 parent report), Multidimensional Fatigue Total Scale Score (alpha = 0.89 child, 0.92 parent report) and most Cancer Module Scales (average alpha = 0.72 child, 0.87 parent report) demonstrated reliability acceptable for group comparisons. Validity was demonstrated using the known-groups method. The PedsQL distinguished between healthy children and children with cancer as a group, and among children on-treatment versus off-treatment. The validity of the PedsQL Multidimensional Fatigue Scale was further demonstrated through hypothesized intercorrelations with dimensions of generic and cancer specific HRQOL. CONCLUSIONS: The results demonstrate the reliability and validity of the PedsQL Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module in pediatric cancer. The PedsQL may be utilized as an outcome measure in clinical trials, research, and clinical practice.

Activities of Daily Living↗
PubMed2006

The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life questionnaire cervical cancer module: EORTC QLQ-CX24.

BACKGROUND: The authors report on the development and validation of a cervical cancer module for the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life (QoL) questionnaire (QLQ), which was designed to assess disease-specific and treatment-specific aspects of QoL in patients with cervical cancer. METHODS: The cervical cancer module (EORTC QLQ-CX24) was developed in a multicultural, multidisciplinary setting to supplement the EORTC QLQ-C30 core questionnaire. The QLQ-C30 and the cervical cancer module were administered to 346 patients with cervical cancer who underwent radical hysterectomy and received radiotherapy and chemotherapy. Psychometric analyses were performed by using data from 2 independent samples. RESULTS: The QLQ-CX24 consists of 3 multiitem scales and 5 single-item scales. Multitrait scaling analyses revealed high internal consistencies for the subscales with Cronbach alpha coefficients ranging from .72 to .87 (Symptom Experience, .72; Body Image, .86; Sexual/Vaginal Functioning, .87). Convergent and discriminant validity were fulfilled with scaling errors below 3%. The QLQ-CX24 was capable of discriminating between clinical subgroups. All items exhibited good compliance with <3% missing values. Most patients completed the EORTC QLQ-C30 and the QLQ-CX24 in <15 minutes (86%), and many did not require any assistance to complete the questionnaires (65%). CONCLUSIONS: The current psychometric analyses supported the content and construct validity and the reliability of the EORTC QLQ-CX24 module. This newly developed module is a useful instrument for assessing the QoL of patients who are treated for cervical cancer both in clinical trials and in clinical practice.

Adult↗
PubMed2004

Principles of spin-echo modulation by J-couplings in magic-angle-spinning solid-state NMR.

In magic-angle-spinning solid-state NMR, the homonuclear J-couplings between pairs of spin-1/2 nuclei may be determined by studying the modulation of the spin echo induced by a pi-pulse, as a function of the echo duration. We present the theory of J-induced spin-echo modulation in magic-angle-spinning solids, and derive a set of modulation regimes which apply under different experimental conditions. In most cases, the dominant spin-echo modulation frequency is exactly equal to the J-coupling. Somewhat surprisingly, the chemical shift anisotropies and dipole-dipole couplings tend to stabilise--rather than abscure--the J-modulation. The theoretical conclusions are supported by numerical simulations and experimental results obtained for three representative samples containing 13C spin pairs.

Anisotropy↗
PubMed1993

Modulation of interferon-gamma receptor during human T lymphocyte alloactivation.

Previous work has shown that neutralization of physiologically secreted interferon(IFN)-gamma or blockade of its receptor during T lymphocyte activation inhibits both proliferation and cytotoxic T lymphocyte generation, suggesting that IFN-gamma plays a crucial role in T lymphocyte induction and differentiation. In this study, the kinetics of the surface expression of the 90-kDa IFN-gamma receptor (IFN-gamma R) was followed during human mixed lymphocyte reaction (MLR) to alloantigens. IFN-gamma R mRNA is constitutively expressed on resting peripheral blood lymphocytes emerging from nylon wood column (NW-PBL) and its expression increases two- to threefold on alloactivated NW-PBL. IFN-gamma R protein is poorly expressed on the membrane of resting CD3+ cells, but up-modulates after 3-day MLR and sharply down-modulates at day 6. Both the p55 and the p75 chains of interleukin-2 receptor (IL-2R) were shown to up-modulate in parallel with IFN-gamma R, whereas they were still highly expressed at day 6. After alloactivation, IFN-gamma and IL-2 secretion starts at 24 h, peaks at day 3 and decreases just when IFN-gamma R and IL-2R begin to up-modulate. Proliferation peaks at day 6. Lastly, stimulation with distinct cell populations showed that the intensity of lymphocyte proliferation, IFN-gamma R membrane up-modulation, and IFN-gamma and IL-2 secretion are regulated in a parallel manner, thus suggesting that they are interrelated. Taken as whole these results demonstrate that increased expression of IFN-gamma R on T lymphocytes can be a critical event during their activation, and strongly support the hypothesis that IFN-gamma/IFN-gamma R interaction provides a signal for its progression.

Cell Line↗
PubMed1998

Effects of protein kinase C modulators on Na+/K+ adenosine triphosphatase activity and phosphorylation in aortae from rats with cirrhosis.

Protein kinase C (PKC) modulates the activity and phosphorylation of the catalytic alpha-subunit of sodium-potassium-adenosine triphosphatase (Na+/K+ ATPase) in normal arteries. Because PKC is altered in cirrhotic aortae, Na+/K+ ATPase may also be altered in these arteries. The aim of the present study was to investigate alpha-subunit activity and phosphorylation in aortae from normal and cirrhotic rats, under baseline conditions and during exposure to PKC modulators. Alpha-subunit activity was assessed by measuring the amount of 32P released by hydrolysis of [gamma-32P]ATP in freshly isolated cell membranes (in the absence of PKC modulators only) and membrane depolarization caused by ouabain-induced alpha-subunit inhibition in isolated aortae (in the absence and presence of PKC modulators). Alpha-subunit phosphorylation was assessed by incorporation of 32P into alpha-subunits. Staurosporine, a PKC inhibitor, and phorbol 12,13-dibutyrate (PDBU), a PKC activator, were used. In addition, alpha-subunit expression was studied by Western blot analysis. In the absence of PKC modulators, the amount of 32P released by hydrolysis of [gamma-32P]ATP and ouabain-induced membrane depolarization were significantly lower in cirrhotic than in normal aortae. Staurosporine suppressed ouabain-induced membrane depolarization in cirrhotic and normal arteries. Ouabain-induced membrane depolarization was similar in cirrhotic aortae exposed to PDBU and in normal arteries studied under baseline conditions. Alpha-subunit phosphorylation was significantly lower in cirrhotic than in normal aortae, in aortae under baseline conditions, and in arteries exposed to staurosporine. Phosphorylation of the alpha-subunit was similar in cirrhotic aortae exposed to PDBU and in normal arteries under baseline conditions. Western blot analysis showed that the amount of alpha-subunit did not significantly differ between cirrhotic and normal aortae. In conclusion, a decrease in baseline Na+/K+ ATPase alpha-subunit activity occurs in aortae from cirrhotic rats as a result of reduced basal PKC activity. This PKC-dependent decreased alpha-subunit activity may be caused by a reduction in PKC-induced alpha-subunit phosphorylation.

Animals↗
PubMed1988

The primary structure of human ribonuclease/angiogenin inhibitor (RAI) discloses a novel highly diversified protein superfamily with a common repetitive module.

Immunological screening of a lambda gt11 library, constructed from HeLa mRNA, yielded several ribonuclease/angiogenin inhibitor (RAI) cDNA clones containing 900-bp inserts. Northern blot analysis revealed that the length of the RAI mRNA is approximately 1.9 kb. Construction and screening of a eukaryotic cDNA expression library (HeLa) containing preferentially complete cDNA inserts led to the isolation of a full length clone. The complete nucleotide sequence was determined. The C-terminal amino acid sequence deduced from the cDNA is identical to the peptide sequence obtained from a CNBr fragment of RAI, confirming the identity of the clone. The deduced primary structure of RAI consists of eight homologous tandem repeats with remarkable periodicity of leucine and cysteine residues. Each repeat is derived from the duplication of a leucine-rich 28-amino-acid module. This prototype module is closely related to a repetitive 24-amino-acid motif of unclear function, previously found in proteins involved in important biological processes such as blood coagulation, embryonic development, cell morphogenesis and signal transduction. Although homologous, the RAI modules show distinct differences in length and amino acid composition to the modules of this group of proteins, demonstrating their high potential of variability, necessary for adaptation to very diverse roles. Based on our results we propose that these repetitive modules are a common structural feature of a novel protein superfamily whose members exert their function by highly specific protein-protein interactions.

Amino Acid Sequence↗
PubMed2007

Tissue factor and thrombomodulin expression on endothelial cell-seeded collagen modules for tissue engineering.

The creation of functional tissue engineering constructs to repair or replace diseased tissues requires a well-formed vasculature network within the construct and the endothelial cells lining that vascular bed must display a nonthrombogenic phenotype. A new approach to tissue engineering involves the assembly of smaller components (modules fabricated at the hundred micron scale) into larger constructs. The modules, collagen gel containing the particular tissue cell of interest, are covered with endothelial cells prior to assembly so that the interconnected channels that are formed are lined with endothelial cells, creating a mimic of a vascular network. Here, we confirmed (using confocal microscopy primarily) that the human umbilical vein endothelial cells, seeded on collagen gel modules without a second embedded cell and without flow, bore the molecular markers of low thrombogenicity. Two days, after seeding on the modules, endothelial cells displayed the typical cobblestone morphology, formed tight cell-cell junctions and covered the whole module surface. Immunofluorescence staining showed that at both 2 days and 7 days after seeding, only a few cells expressed tissue factor while this number was dramatically increased after TNFalpha stimulation. On the other hand, thrombomodulin was expressed by the majority of seeded cells and expression was reduced after TNFalpha stimulation.

Collagen↗
PubMed2006

Cyclic compression of chondrocytes modulates a purinergic calcium signalling pathway in a strain rate- and frequency-dependent manner.

Mechanical loading modulates cartilage homeostasis through the control of matrix synthesis and catabolism. However, the mechanotransduction pathways through which chondrocytes detect different loading conditions remain unclear. The present study investigated the influence of cyclic compression on intracellular Ca2+ signalling using the well-characterised chondrocyte-agarose model. Cells labelled with Fluo4 were visualised using confocal microscopy following a period of 10 cycles of compression between 0% and 10% strain. In unstrained agarose constructs, not subjected to cyclic compression, a subpopulation of approximately 45% of chondrocytes exhibited spontaneous global Ca2+ transients with mean transient rise and fall times of 19.4 and 29.4 sec, respectively. Cyclic compression modulated global Ca2+ signalling by increasing the percentage of cells exhibiting Ca2+ transients (population modulation) and/or reducing the rise and fall times of these transients (transient shape modulation). The frequency and strain rate of compression differentially modulated these Ca2+ signalling characteristics providing a potential mechanism through which chondrocytes may distinguish between different loading conditions. Treatment with apyrase, gadolinium and the P2 receptor blockers, suramin and basilen blue, significantly reduced the percentage of cells exhibiting Ca2+ transients following cyclic compression, such that the mechanically induced upregulation of Ca2+ signalling was completely abolished. Thus cyclic compression appears to activate a purinergic pathway involving the release of ATP followed by the activation of P2 receptors causing a combination of extracellular Ca2+ influx and intracellular Ca2+ release. Knowledge of this fundamental cartilage mechanotransduction pathway may lead to improved therapeutic strategies for the treatment of cartilage damage and disease.

Animals↗
PubMed1991

Real space modulation in Bi2Sr2CanCun + 1O6+2n and Tl2Ba2CuO6 superconductors derived from electron diffraction information.

We will try to illustrate here that, simply from the geometry of the electron diffraction pattern of an incommensurably modulated structure, conclusive information can be obtained on the real space shape of this modulation. The method applied here is based on the 3 + 1 dimensional description of symmetry operations and can be summarized as follows: 1) reconstruct the three-dimensional reciprocal space geometry of the modulated structure from electron diffraction information along different zone axes; 2) deduce the complete Bravais type symbol of the four-dimensional structure from the general reflection conditions; and 3) derive the modulation function for each atom type from the superspace symmetry elements which result from the information of both modulation and basic structure. This method will be applied here in short on the Bi2Sr2CanCun + 1O6+2n strucutre, for which system the results are in agreement with the ones recently obtained from neutron diffraction. For Tl2Ba2CuO6 where no data from other diffraction techniques are available, a more complete calculation will be performed, in order to determine the shape of the displacement function for the different atom types; the results are in agreement with the observed High Resolution Electron Microscopy (HREM) images.

Bismuth↗
PubMed2004

Investigation into factors affecting precision in ion trap mass spectrometry using different scan directions and axial modulation potential amplitudes.

Electrospray ionization mass spectra obtained from different scan directions are observed to be dependent on the axial modulation potential amplitudes used for resonant ejection and on the positive deviation caused by higher even-multipole fields present in most commercial ion traps. The axial modulation voltage influences the dissociation of ions during resonant ejection and the observed mass shifts. The higher even-multipole fields in commercial ion traps are known to influence resonant ejection from the ion trap and can cause a loss in mass resolution for peaks in reverse scan mass spectra compared with that obtained by the forward scan. However, along with the dissociation of ions during resonant ejection causing a loss in resolution, the possibility of resolving an isotopic distribution is also shown to be influenced by the mass shifts caused by the space charge. These mass shifts differ depending on the scan direction employed. A significant loss in resolution can also result from resonant ejection using non-optimal axial modulation voltages. We also present results showing the ejection of ions at betaz = 1/2 using the reverse scan mode without the axial modulation voltage. Ion ejection at betaz = 1/2 is uncommon in commercial (stretched ion traps) with the conventional analytical scan without the use of a frequency of the axial modulation voltage corresponding to this non-linear resonance.

Cytochromes c↗