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M Palmer

Publications and source records attributed to M Palmer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Search for the decay upsilon(1S) --> gammaeta(').

We report on a search for the radiative decay Upsilon(1S)-->gammaeta(') in 61.3 pb(-1) of data taken with the CLEO II detector at the Cornell Electron Storage Ring. Three decay chains were investigated, all involving eta(')-->pi(+)pi(-)eta, followed by eta-->gammagamma, eta-->pi(0)pi(0)pi(0), or eta-->pi(+)pi(-)pi(0). We find no candidate events in any of the three cases and set a combined upper limit of 1.6x10(-5) at 90% C.L., significantly smaller than the previous limit. We compare our result to other radiative Upsilon decays, to radiative J/psi decays, and to theoretical predictions.

Journal Article↗
PubMed2001

Bounds on the CP asymmetry in like-sign dileptons from B(0)B*(0) meson decays.

We have measured the charge asymmetry in like-sign dilepton yields from B(0)B*(0) meson decays using the CLEO detector at the Cornell Electron Storage Ring. We find a(0)(ll) identical with[N(l(+)l(+))-N(l(-)l(-))]/[N(l(+)l(+))+N(l(-)l(-))] = +0.013+/-0.050+/-0.005. We combine this result with a previous, independent measurement and obtain Re(epsilon(B))/(1+ the absolute value of epsilon(B)(2)) = +0.0035+/-0.0103+/-0.0015 (uncertainties are statistical and systematic, respectively) for the CP impurity parameter, epsilon(B).

Journal Article↗
PubMed2001

Observation of new states decaying into Lambda+(c)pi(-)pi(+).

Using 13.7 fb(-1) of data recorded by the CLEO detector at the Cornell Electron Storage Ring, we investigate the spectrum of charmed baryons which decay into Lambda+(c)pi(-)pi(+) and are more massive than the Lambda+(c)(2625) baryon. We find evidence for two new states: one is broad and has an invariant mass roughly 480 MeV above that of the Lambda+(c) baryon; the other is narrow with an invariant mass of 596+/-1+/-2 MeV above the Lambda+(c) mass.

Journal Article↗
PubMed2001

Evidence of New States Decaying into Xi(*)(c)pi.

Using 13.7 fb(-1) of data recorded by the CLEO detector at Cornell Electron Storage Ring, we report evidence of two new charmed baryons: one decaying into Xi(0')(c)pi(+) with the subsequent decay Xi(0')(c)-->Xi(0)(c)gamma, and its isospin partner decaying into Xi(+')(c)pi(-) followed by Xi(+')(c)-->Xi(+)(c)gamma. We measure the following mass differences for the two states: M(Xi(0)(c)gammapi(+))-M(Xi(0)(c)) = 318.2+/-1.3+/-2.9 MeV and M(Xi(+)(c)gammapi(-))-M(Xi(+)(c)) = 324.0+/-1.3+/-3.0 MeV. We interpret these new states as the J(P) = 1 / 2(-) Xi(c1) particles, the charmed-strange analogs of the Lambda(+)(c1)(2593).

Journal Article↗
PubMed2001

Observation of B --> phiK and B --> phiK*.

We have studied two-body charmless hadronic decays of B mesons into the final states straight phiK and phiK(*). Using 9.7 million B&Bmacr; pairs collected with the CLEO II detector, we observe the decays B- --> phiK- and B0--> phiK(*0) with the following branching fractions: B(B--->phiK-) = (5.5(+2.1)(-1.8)+/-0.6)x10(-6) and B(B0--> phiK(*0)) = (11.5(+4.5+1.8)(-3.7-1.7))x10(-6). We also see evidence for the decays B0-->phiK0 and B---> phiK(*-). However, since the statistical significance is not overwhelming for these modes, we determine upper limits of <12.3x10(-6) and <22.5x10(-6) ( 90% confidence level), respectively.

Journal Article↗
PubMed2001

Observation of the Omega(0)(c) Charmed Baryon at CLEO.

The CLEO experiment at the CESR collider has used 13.7 fb(-1) of data to search for the production of the Omega(0)(c) (css ground state) in e(+)e(-) collisions at square root of (s) approximately 10.6 GeV. The modes used to study the Omega(0)(c) are Omega(-)pi(+), Omega(-)pi(+)pi(0), Xi-K-pi(+)pi(+), Xi0K-pi(+), and Omega(-)pi(+)pi(+)pi(-). We observe a signal of 40.4+/-9.0(stat) events at a mass of 2694.6+/-2.6(stat)+/-1.9(syst) MeV/c(2), for all modes combined.

Journal Article↗
PubMed2001

Search for B --> tau(nu) and B --> K(nu)nu.

We report results of a search for B-->tau(nu) in a sample of 9.7 x 10(6) charged B meson decays. We exclusively reconstruct the companion B decay to suppress background. We set an upper limit on the branching fraction B(B-->tau(nu))<8.4 x 10(-4) at 90% confidence level. We also establish B(B+/--->K+/-nu(nu))<2.4 x 10(-4) at 90% confidence level.

Journal Article↗
PubMed2001

Measurement of the relative branching fraction of upsilon(4S) to charged and neutral B-meson pairs.

We analyze 9.7x10(6) B_B pairs recorded with the CLEO detector to determine the production ratio of charged to neutral B-meson pairs produced at the Upsilon(4S) resonance. We measure the rates for B0-->J/psiK((*)0) and B+-->J/psiK((*)+) decays and use the world-average B-meson lifetime ratio to extract the relative widths f(+-) / f(00) = gamma(Upsilon(4S)-->B+B-) / gamma(Upsilon(4S)-->B0 B-0)) = 1.04+/-0.07(stat)+/-0.04(syst). With the assumption that f(+-)+f(00) = 1, we obtain f(00) = 0.49+/-0.02(stat)+/-0.01(syst) and f(+-) = 0.51+/-0.02(stat)+/-0.01(syst). This production ratio and its uncertainty apply to all exclusive B-meson branching fractions measured at the Upsilon(4S) resonance.

Journal Article↗
PubMed2001

Measurement of the lambda(+)(c) lifetime.

The Lambda+c lifetime is measured using 9.0 fb(-1) of e+e- annihilation data collected on or just below the Upsilon(4S) resonance with the CLEO II.V detector at CESR. Using an unbinned maximum likelihood fit, the Lambda+c lifetime is measured to be 179.6+/-6.9(stat)+/-4.4(syst) fs. The precision of this colliding beam measurement is comparable to other measurements, which are based on fixed-target experiments, with different systematic uncertainties.

Journal Article↗
PubMed2001

Streptolysin O: the C-terminal, tryptophan-rich domain carries functional sites for both membrane binding and self-interaction but not for stable oligomerization.

Streptolysin O belongs to the class of thiol-activated toxins, which are single chain, four-domain proteins that bind to membranes containing cholesterol and then assemble to form large oligomeric pores. Membrane binding involves a conserved tryptophan-rich sequence motif located within the C-terminally located domain 4. In contrast, sites involved in oligomerization and pore formation have been assigned to domains 1 and 3, respectively. We here examined the functional properties of domain 4, which was recombinantly expressed with an N-terminal histidine tag for purification and an additional cysteine residue for covalent labeling. The fluorescently labeled fragment readily bound to membranes, but it did not form oligomers nor lyse cell membranes. Moreover, the labeled fragment did not detectably become incorporated into hybrid oligomers when combined with lytically active full-length toxin. However, when present in large excess over the active toxin, the domain 4 fragment effected reduction of hemolytic activity and of functional pore size, which indicates interference with oligomerization of the lytically active species. Our findings support the notion that domain 4 of the streptolysin O molecule may fold autonomously, is essential for membrane binding and is capable not of irreversible but of reversible association with the entire toxin molecule.

Bacterial Proteins↗
PubMed2001

Coupling of cholesterol and cone-shaped lipids in bilayers augments membrane permeabilization by the cholesterol-specific toxins streptolysin O and Vibrio cholerae cytolysin.

Vibrio cholerae cytolysin (VCC) forms oligomeric pores in lipid bilayers containing cholesterol. Membrane permeabilization is inefficient if the sterol is embedded within bilayers prepared from phosphatidylcholine only but is greatly enhanced if the target membrane also contains ceramide. Although the enhancement of VCC action is stereospecific with respect to cholesterol, we show here that no such specificity applies to the two stereocenters in ceramide; all four stereoisomers of ceramide enhanced VCC activity in cholesterol-containing bilayers. A wide variety of ceramide analogs were as effective as D-erythro-ceramide, as was diacylglycerol, suggesting that the effect of ceramide exemplifies a general trend of lipids with a small headgroup to augment the activity of VCC. Incorporation of these cone-shaped lipids into cholesterol-containing bilayers also gave similar effects with streptolysin O, another cholesterol-specific but structurally unrelated cytolysin. In contrast, the activity of staphylococcal alpha-hemolysin, which does not share with the other toxins the requirement for cholesterol, was far less affected by the presence of lipids with a conical shape. The collective data indicate that sphingolipids and glycerolipids do not interact with the cytolysins specifically. Instead, lipids that have a conical molecular shape appear to effect a change in the energetic state of membrane cholesterol that in turn augments the interaction of the sterol with the cholesterol-specific cytolysins.

Bacterial Proteins↗
PubMed2001

Membrane insertion of the heptameric staphylococcal alpha-toxin pore. A domino-like structural transition that is allosterically modulated by the target cell membrane.

Staphylococcal alpha-toxin forms heptameric pores on eukaryotic cells. After binding to the cell membrane in its monomeric form, the toxin first assembles into a heptameric pre-pore. Subsequently, the pre-pore transforms into the final pore by membrane insertion of an amphipathic beta-barrel, which comprises the "central loop" domains of all heptamer subunits. The process of membrane insertion was analyzed here using a set of functionally altered toxin mutants. The results show that insertion may be initiated within an individual protomer when its NH2 terminus activates its central loop. The activated state is then shared with the central loops of the residual heptamer subunits, which results in cooperative membrane penetration. This cooperation of the central loops commences while these are still remote from the lipid bilayer. Nevertheless, it is subject to modulation by the target membrane, which therefore acts across a distance much like an allosteric effector. However, while allosteric transitions usually are reversible, membrane insertion of alpha-toxin is an irreversible event, and we show here that it can proceed to completion in a domino-like fashion when triggered by as little as a single foreign atom within the entire heptamer.

Allosteric Regulation↗
PubMed2001

Potassium and calcium current blocking properties of the novel antiarrhythmic agent H 345/52: implications for proarrhythmic potential.

OBJECTIVES: To study the blocking effects of H 345/52 on ionic currents of rabbit ventricular myocytes and how these features translate into a proarrhythmic potential. METHODS: The single electrode voltage clamp technique was used to study the effects of H 345/52 on the rapid component of the delayed rectifying potassium current, I(Kr), and the L-type calcium current (I(Ca)). Differential effects of H 345/52 and almokalant on APD prolongation were studied in a rabbit Purkinje fibre/ventricular muscle preparation. The temporal variability of the action potential duration (APD) and its relation to proarrhythmias was examined in Langendorff-perfused rabbit hearts administered H 345/52 or almokalant. Anaesthetised, methoxamine-sensitised rabbits were used to assess the propensity of intravenous H 345/52 and ibutilide to induce torsades de pointes (TdP). RESULTS: H 345/52 potently blocked I(Kr) (IC(50)=40 nM) without consequential use-dependency. The I(Ca) was also blocked, but at higher concentrations (IC(50)=1.3 microM). Block of I(Ca) was markedly frequency-dependent (positive) and influenced by membrane potential, such that H 345/52 was more effective following clamp steps from plateau potentials than from -80 mV. In the Purkinje fibre-ventricular muscle preparation, almokalant prolonged the Purkinje fibre APD preferentially, whereas H 345/52 homogeneously prolonged APD in both tissue types. In the perfused rabbit heart, H 345/52 (1 microM) and almokalant (0.3 microM) prolonged APD to a similar degree but increased the temporal variability of APD differently, from 3+/-0.4 ms in control hearts to 8+/-1.2 ms and to 38+/-7.5 ms (P<0.001 vs. H 345/52), respectively. Unequivocal early after-depolarisations were seen in 5/6 almokalant-perfused hearts but in no heart administered H 345/52 (P<0.05). In anaesthetised rabbits, H 345/52 (17.4 micromol/kg) or ibutilide (2.6 micromol/kg maximum), maximally lengthened the QT interval from 133+/-4.5 to 177+/-8.0 ms and from 125+/-5.1 to 166+/-9.3 ms (P<0.001, n=8). However, whereas ibutilide induced TdP in all animals at 0.06+/-0.009 micromol/kg, H 345/52 did not induce TdP (P=0.0002) at up to 17.4 micromol/kg. CONCLUSIONS: H 345/52 blocks I(Kr) with high potency and I(Ca) with somewhat lower potency and was found to delay ventricular repolarisation without substantially increasing temporal or spatial dispersion and without inducing early after-depolarisations or TdP.

Action Potentials↗
PubMed2001

On-line coupling of partial filling-capillary zone electrophoresis with mass spectrometry for the separation of clenbuterol enantiomers.

The on-line coupling of capillary zone electrophoresis with mass spectrometry (CZE-MS) for the separation of enantiomers is hampered by the presence of nonvolatile chiral selectors such as cyclodextrins in the separation buffer. This problem can be overcome by use of the partial filling technique where only a part of the capillary is filled with the separation buffer containing chiral selectors. Since the electroosmotic flow is almost completely suppressed at acidic pH, that dimethyl-beta-cyclodextrin is neutral, no free cyclodextrin would reach the MS detector when using a partially filled capillary. By this method, clenbuterol enantiomers were successfully resolved and separated from salbutamol (internal standard) in aqueous solution and in plasma samples. A solid-phase extraction (SPE) was used for the preparation of plasma samples before analysis.

Clenbuterol↗
PubMed2001

The family of thiol-activated, cholesterol-binding cytolysins.

Several species of both pathogenic and non-pathogenic grampositive bacteria within the genera Streptococcus, Clostridium and Bacillus secrete cytolytic proteins that belong to a single, highly homologous family. The most widely known members of this family are streptolysin O, listeriolysin, perfringolysin, and pneumolysin. These toxins specifically require membrane cholesterol but, apparently, do not depend on any other specific cell surface receptor, so that they are able to lyse the cytoplasmic membranes of virtually any animal cell. Upon binding as monomers, they oligomerize to form large pores with up to 30 nm internal diameter. These are the largest pores known, permitting permeation not only of ions and small metabolites but also of macromolecules. The latter property renders these toxins useful tools in cell biology. While several of these cytolysins have been shown to be determinants of bacterial pathogenicity, their biological roles may vary, as do the lifestyles of the bacteria secreting them. A unique function is surely fulfilled by listeriolysin O, which helps the intracellular pathogen Listeria monocytogenes escape from phagolysosomes and then spread to adjacent host cells.

Animals↗
PubMed2001

Interaction of Escherichia coli hemolysin with biological membranes. A study using cysteine scanning mutagenesis.

Escherichia coli hemolysin (HlyA) is a membrane-permeabilizing protein belonging to the family of RTX-toxins. Lytic activity depends on binding of Ca2(+) to the C-terminus of the molecule. The N-terminus of HlyA harbors hydrophobic sequences that are believed to constitute the membrane-inserting domain. In this study, 13 HlyA cysteine-replacement mutants were constructed and labeled with the polarity-sensitive fluorescent probe 6-bromoacetyl-2-dimethylaminonaphthalene (badan). The fluorescence emission of the label was examined in soluble and membrane-bound toxin. Binding effected a major blue shift in the emission of six residues within the N-terminal hydrophobic domain, indicating insertion of this domain into the lipid bilayer. The emission shifts occurred both in the presence and absence of Ca2(+), suggesting that Ca2(+) is not required for the toxin to enter membranes. However, binding of Ca2(+) to HlyA in solution effected conformational changes in both the C-terminal and N-terminal domain that paralleled activation. Our data indicate that binding of Ca2(+) to the toxin in solution effects a conformational change that is relayed to the N-terminal domain, rendering it capable of adopting the structure of a functional pore upon membrane binding.

2-Naphthylamine↗
PubMed2001

Application of beta-galactosidase enzyme complementation technology as a high throughput screening format for antagonists of the epidermal growth factor receptor.

We have applied enzyme complementation technology to develop a screen for antagonists of the epidermal growth factor (EGF) receptor. Chimeric proteins containing two weakly complementing deletion mutants of Escherichia coli beta-galactosidase (beta-gal), each fused to the EGF receptor extracellular and transmembrane domains, have been stably expressed in C2C12 cells. In this cell line, formation of active beta-gal is dependent on agonist-stimulated dimerization of the EGF receptor. We have developed a homogenous 384-well assay protocol and have applied this to characterize the pharmacology of the receptor and to develop a high throughput screen (HTS) for EGF receptor antagonists. The assay is tolerant to DMSO concentrations of up to 2% and, across 21 passages in culture, exhibits an EC(50) for EGF of 5.4 +/- 3.6 ng/ml (n = 11) and a Z' of 0.55 +/- 0.13 (n = 11). A random set of 1,280 compounds was screened in duplicate at 11 microM to examine the robustness of enzyme complementation technology and to characterize the false-positive hit rate in the assay. Using a cutoff of 40% inhibition of EGF-promoted beta-gal activity, the hit rate on day 1 was 2.5% and on day 2 was 1.9%. After retesting the active compounds, the hit rate was reduced to 0.4%, of which one of the compounds was identified as a beta-gal inhibitor and the remainder appeared to be nonspecific inhibitors in the assay. This technology is amenable to automated screen workstations, there are highly sensitive chemiluminescent and fluorescent beta-gal assay reagents amenable to detection in miniaturized plate formats, and the assay benefits from a low false-positive hit rate. Enzyme complementation technology may have wide application within the HTS environment for the detection of modulators of receptor activation or inhibitors of protein-protein interactions in mammalian cells.

Animals↗