Biomedical subjects

T F Gallagher

Publications and source records attributed to T F Gallagher.

At least 19 recordsLinked to original sources

PubMed2006

Coherent population transfer in an atom by multiphoton adiabatic rapid passage.

Coherent population transfer in an atom using a sequence of adiabatic rapid passages through single-photon resonances is well-known, but it requires that the frequency sweep match the changing frequencies of the atomic transitions. The same population transfer can be effected via a single multiphoton adiabatic rapid passage, which requires only a small frequency sweep, if it is possible to select the desired multiphoton transition from the many possible transitions. Here we report the observation of population transfer between Rydberg states by high order multiphoton adiabatic rapid passage.

Journal Article↗

PubMed2005

Dipole-dipole excitation and ionization in an ultracold gas of Rydberg atoms.

In cold dense Rydberg atom samples, the dipole-dipole interaction strength is effectively resonant at the typical interatomic spacing in the sample, and the interaction has a 1/R3 dependence on interatomic spacing R. The dipole-dipole attraction leads to ionizing collisions of initially stationary atoms, which produces hot atoms and ions and initiates the evolution of initially cold samples of neutral Rydberg atoms into plasmas. More generally, the strong dipole-dipole forces lead to motion, which must be considered in proposed applications.

Journal Article↗

PubMed2005

Microwave manipulation of an atomic electron in a classical orbit.

Although an atom is a manifestly quantum mechanical system, the electron in an atom can be made to move in a classical orbit almost indefinitely if it is exposed to a weak microwave field oscillating at its orbital frequency. The field effectively tethers the electron, phase-locking its motion to the oscillating microwave field. By exploiting this phase-locking, we have sped up or slowed down the orbital motion of the electron in excited lithium atoms by increasing or decreasing the microwave frequency between 13 and 19 gigahertz; the binding energy and orbital size change concurrently.

Journal Article↗

PubMed2004

Quantum suppression of microwave ionization of Rydberg atoms at high scaled frequency.

Microwave ionization of Rydberg atoms is well described as the onset of classical chaos when the microwave frequency omega is less than the Kepler frequency 1/n(3). However, when omega>1/n(3), i.e., at high scaled frequency Omega=omegan(3)>1, classical ionization is predicted to be suppressed by quantum interference, an analogue to Anderson localization in a solid. Using 17.55 GHz microwave fields we have observed the ionization of Sr Rydberg atoms in the regime 1</=Omega</=5 . Our measurements demonstrate the quantum suppression of classical diffusive ionization and show the ionization field to be n independent in this regime.

Journal Article↗

PubMed2004

Nondispersing wave packets.

We have formed nondispersing wave packets from atomic Li Rydberg eigenstates by adding a small microwave field approximately resonant with the Deltan=1 transition. The orbital motion of the Rydberg electron in states of 70<or=n<or=78 becomes phase locked to a 17.5 GHz microwave field and remains so for 900 ns, roughly 15 000 orbits of the Rydberg electron. A Floquet approach provides a reasonable quantum-mechanical description.

Journal Article↗

PubMed2003

Fano line shapes reconsidered: symmetric photoionization peaks from pure continuum excitation.

In a photoionization spectrum in which there is no excitation of the discrete states, but only the underlying continuum, we have observed resonances which appear as symmetric peaks, not the commonly expected window resonances. Furthermore, since the excitation to the unperturbed continuum vanishes, the cross section expected from Fano's configuration interaction theory is identically zero. This shortcoming is removed by the explicit introduction of the phase shifted continuum, which demonstrates that the shape of a resonance, by itself, provides no information about the relative excitation amplitudes to the discrete state and the continuum.

Journal Article↗

PubMed2001

Pyrimidinylimidazole inhibitors of p38: cyclic N-1 imidazole substituents enhance p38 kinase inhibition and oral activity.

Optimization of a series of N-1-cycloalkyl-4-aryl-5-(pyrimidin-4-yl)imidazole inhibitors of p38 kinase is reported. Oral administration of inhibitors possessing a cyclohexan-4-ol or piperidin-4-yl group at N-1 in combination with alkoxy, amino(alkyl), phenoxy and anilino substitution at the 2-position of the pyrimidine was found to potently inhibit LPS-induced TNF in mice and rats. The selectivity of these new inhibitors for p38 kinase versus eight other protein kinases is high and in all cases exceeds that of SB 203580.

Administration, Oral↗

PubMed2001

Microwave ionization of an atomic electron wave packet.

A short microwave pulse is used to ionize a lithium Rydberg wave packet launched from the core at a well-defined phase of the field. We observe a strong dependence on the relative phase between the motion of the wave packet and the oscillations of the field. This phase dependent ionization is also studied as a function of the relative frequency. Our experimental observations are in good qualitative agreement with a one-dimensional classical model of wave packet ionization.

Journal Article↗

PubMed2001

Phenoxypyrimidine inhibitors of p38alpha kinase: synthesis and statistical evaluation of the p38 inhibitory potencies of a series of 1-(piperidin-4-yl)-4-(4-fluorophenyl)-5-(2-phenoxypyrimidin-4-yl) imidazoles.

As a continuation of our work with 1,4,5 substituted imidazole inhibitors of p38alpha, we report a series of 1-(4-piperidinyl)-4-(4-fluorophenyl)-5-(2-phenoxy-4-pyrimidinyl) imidazoles related to 7. The compounds have IC50's for inhibition of p38alpha ranging from 6.0 to 650nM. Statistical analysis of the p38beta inhibitor potencies shows a correlation of IC50's with the electron donating strength of low molecular weight substituents.

Enzyme Inhibitors↗

PubMed2000

Characterization of auxin-induced ARRO-1 expression in the primary root of Malus domestica.

ARRO-1, a novel 2-oxoacid-dependent dioxygenase (2-ODD) is up-regulated during IBA-induced adventitious root formation in stem discs of Malus domestica. Analysis of ARRO-1's expression profile in the primary root of apple seedlings indicates that it is also highly up-regulated in the root in response to both IAA and IBA, but not 2, 4-D. Auxin-derived evolution of ethylene can be discounted as the source of ARRO-1 induction as ARRO-1 is not induced in the root following treatment with the ethylene precursor ACC. Constitutive expression in the primary root further suggests that ARRO-1's role may be linked to the regulation of natural auxin levels within plant tissues. Significantly, orthologues of ARRO-1 have been identified in Arabidopsis thaliana by means of DNA database analysis which will enable the further molecular characterization of this class of 2-ODD.

Amino Acid Sequence↗

PubMed1999

The diagnosis of freemartinism in cattle using sex-specific DNA sequences.

The majority of heifers born co-twins to bulls are infertile freemartins. It is important that the condition be diagnosed at an early age as freemartins have no potential for use as replacement stock. A rapid, robust, reliable technique for freemartin diagnosis is described. Three Y-specific polymerase chain reaction (PCR) primer pairs: BOV97M, BRY.1 and AMX/Y were used to detect male cells in the blood of heifers born co-twins to bulls. PCR -based tests have advantages over currently used methods of freemartin diagnosis.

Animals↗

PubMed1998

Pyrimidinylimidazole inhibitors of CSBP/p38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes.

Pyrimidine analogs of the pyrimidinylimidazole class of CSBP/p38 kinase inhibitors were prepared in an effort to reduce the potent inhibition of hepatic cytochrome P450 observed for the pyridinyl compounds. The substitution of pyrimidin-4-yl, 2-methoxypyrimidin-4-yl, or 2-methylaminopyrimidin-4-yl for pyridin-4-yl effectively dissociates CSBP/p38 kinase from P450 inhibition for this series and furthermore achieves an increase in oral activity.

Animals↗

PubMed1998

Gene expression during adventitious root formation in apple.

A model system for adventitious root formation in woody plants was used to identify transcripts that are up-regulated during this process. 1 mm stem-disks from micropropagated shoots of the apple cultivar Jork 9 can be induced to form roots by treatment with the auxin indole butyric acid (IBA). Stem discs are placed on medium containing IBA for 24 hours and then transferred to IBA-free medium. Root initials become visible after 5-6 days and root elongation occurs within 7-9 days. The first visible cell divisions, which will give rise to the adventitious roots, are detectable 48 hours following IBA treatment. We have used this system to identify transcripts that are induced during adventitious root formation. Two techniques were employed in this analysis: differential messenger RNA display (DDRT) and mRNA representational difference analysis (RDA), a technique that couples PCR and subtractive hybridisation. Using both of these techniques a number of clones have been isolated that exhibit differential expression during auxin induced root formation. Both up-regulated and down-regulated transcripts have been identified. Expression of these genes has initially been verified by reverse northern blot analysis. Northern blot analysis with individual clones has confirmed the expression pattern observed in the reverse northern analysis. Tentative identities of some of the clones have been established by sequencing the partial cDNAs. Among the up-regulated transcripts are clones that share sequence homology with polygalacturonase and MAP kinases. A full-length cDNA for the most abundant up-regulated mRNA, a 2-oxoacid dependent dioxygenase, was characterised. This mRNA is expressed between 24 and 72 hours following IBA treatment of apple stem disks.

Amino Acid Sequence↗

PubMed1997

Pyridinyl imidazole inhibitors of p38 mitogen-activated protein kinase bind in the ATP site.

The site of action of a series of pyridinyl imidazole compounds that are selective inhibitors of p38 mitogen-activated protein kinase in vitro and block proinflammatory cytokine production in vivo has been determined. Using Edman sequencing, 125I-SB206718 was shown to cross-link to the nonphosphorylated Escherichia coli-expressed p38 kinase at Thr175, which is proximal to the ATP binding site. Titration calorimetric studies with E. coli-expressed p38 kinase showed that SB203580 bound with a stoichiometry of 1:1 and that binding was blocked by preincubation of p38 kinase with the ATP analogue, FSBA (5'-[p-(fluorosulfonyl)benzoyl]adenosine), which covalently modifies the ATP binding site. The intrinsic ATPase activity of the nonphosphorylated enzyme was inhibited by SB203580 with a Km of 9.6 mM. Kinetic studies of active, phosphorylated yeast-expressed p38 kinase using a peptide substrate showed that SB203580 was competitive with ATP with a Ki of 21 nM and that kinase inhibition correlated with binding and biological activity. Mutagenesis indicated that binding of 125I-SB206718 was dependent on the catalytic residues K53 and D168 in the ATP pocket. These findings indicate that the pyridinyl imidazoles act in vivo by inhibiting p38 kinase activity through competition with ATP and that their selectivity is probably determined by differences in nonconserved regions within or near the ATP binding pocket.

Adenosine↗

PubMed1997

Regulation of stress-induced cytokine production by pyridinylimidazoles; inhibition of CSBP kinase.

Members of three classes of pyridinylimidazoles bind with varying affinities to CSBP (p38) kinase which is a member of a stress-induced signal transduction pathway. Based upon SAR and protein homology modeling, the pharmacophore and three potential modes of binding to the enzyme are presented. For a subset of pyridinylimidazoles, binding is shown to correlate with inhibition of CSBP kinase activity, whereas no significant inhibition of PKA, PKC alpha and ERK kinase activity is observed.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1996

1-substituted 4-aryl-5-pyridinylimidazoles: a new class of cytokine suppressive drugs with low 5-lipoxygenase and cyclooxygenase inhibitory potency.

A series of 1-alkyl- or -aryl-4-aryl-5-pyridinylimidazoles (A) were prepared and tested for their ability to bind to a recently discovered protein kinase termed CSBP and to inhibit lipopolysaccharide (LPS)-stimulated TNF production in mice. The kinase, CSBP, appears to be involved in a signaling cascade initiated by a number of inflammatory stimuli and leading to the biosynthesis of the inflammatory cytokines IL-1 and TNF. Two related imidazole classes (B and C) had previously been reported to bind to CSBP and to inhibit LPS-stimulated human monocyte IL-1 and TNF production. The members of the earlier series exhibited varying degrees of potency as inhibitors of the enzymes of arachidonic acid metabolism, PGHS-1 and 5-LO. Several of the more potent CSBP ligands and TNF biosynthesis inhibitors among the present series of N-1-alkylated imidazoles (A) were tested as inhibitors of PGHS-1 and 5-LO and were found to be weak to inactive as inhibitors of these enzymes. One of the compounds, 9 (SB 210313) which lacked measureable activity as an inhibitor of the enzymes of arachidonate metabolism, and had good potency in the binding and in vivo TNF inhibition assays, was tested for antiarthritic activity in the AA rat model of arthritis. Compound 9 significantly reduced edema and increased bone mineral density in this model.

Animals↗

PubMed1995

SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1.

A class of pyridinyl imidazoles inhibit the MAP kinase homologue, termed here reactivating kinase (RK) [Lee et al. (1994) Nature 372, 739-746]. We now show that one of these compounds (SB 203580) inhibits RK in vitro (IC50 = 0.6 microM), suppresses the activation of MAPKAP kinase-2 and prevents the phosphorylation of heat shock protein (HSP) 27 in response to interleukin-1, cellular stresses and bacterial endotoxin in vivo. These results establish that MAPKAP kinase-2 is a physiological RK substrate, and that HSP27 is phosphorylated by MAPKAP kinase-2 in vivo. The specificity of SB 203580 was indicated by its failure to inhibit 12 other protein kinases in vitro, and by its lack of effect on the activation of RK kinase and other MAP kinase cascades in vivo. We suggest that SB 203580 will be useful for identifying other physiological roles and targets of RK and MAPKAP kinase-2.

Amino Acid Sequence↗

PubMed1994

A PCR-based sex-determination assay in cattle based on the bovine amelogenin locus.

A method for determining the sex of bovine embryos has been established. Primers for a portion of the bovine amelogenin locus (AMX/Y) were used to amplify DNA present in either 0.1 microliter of blood or biopsies taken from 6-7-day-old embryos. The primers amplify a 280 bp band in females and a 280 and 217 bp bands in males. The method is rapid, does not require prior purification of DNA and contains an internal control which detects PCR failure.

Amelogenin↗