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Biomedical subjects

W D Phillips

Publications and source records attributed to W D Phillips.

At least 19 recordsLinked to original sources
PubMed2003

Quantum information with neutral atoms as qubits.

One of the essential features of a quantum computer is a quantum 'register' of well-characterized qubits. Neutral atoms in optical lattices are a natural candidate for such a register. We have demonstrated a patterned-loading technique that can be used to load atoms into large arrays of tightly confined but optically resolvable lattice sites. We have also seen preliminary indications of the Mott-insulator transition, which provides a route for single-atom initialization of the individual sites. Combining the two experiments should allow for large arrays of individually addressable single atoms, a system which provides a starting point for further quantum computation studies.

Journal Article↗
PubMed2003

Regional differences in sympathetic purinergic transmission along the length of the mouse vas deferens.

Contraction of the smooth muscle in the mouse vas deferens is elicited by sympathetic nerves releasing at least two neurotransmitters, adenosine triphosphate (ATP) and noradrenaline (NA). Several studies have indicated the presence of regional variation in the purinergic and noradrenergic contributions to sympathetic nerve-evoked contractions in rodent vasa deferentia. We examined the relative contribution of ATP and NA to neurotransmission and contraction at the prostatic and epididymal ends of the mouse vas deferens. The success rate of recording excitatory junction currents (EJCs, extracellular indication of ATP release) from varicosities at the prostatic end of the vas deferens was eight times greater than for varicosities located at the epididymal end. Both regions of the vas deferens responded similarly to focal application of NA and ATP. Furthermore, the relative density and distribution of P2X(1)-receptor mRNA and anti-P2X(1) immunostaining did not differ between the two regions. Our results suggest that most varicosities located at the epididymal end of the vas deferens are releasing an insufficient amount of ATP to evoke detectable EJCs.

Adenosine Triphosphate↗
PubMed2002

Nonlinear and quantum atom optics.

Coherent matter waves in the form of Bose-Einstein condensates have led to the development of nonlinear and quantum atom optics - the de Broglie wave analogues of nonlinear and quantum optics with light. In nonlinear atom optics, four-wave mixing of matter waves and mixing of combinations of light and matter waves have been observed; such progress culminated in the demonstration of phase-coherent matter-wave amplification. Solitons represent another active area in nonlinear atom optics: these non-dispersing propagating modes of the equation that governs Bose-Einstein condensates have been created experimentally, and observed subsequently to break up into vortices. Quantum atom optics is concerned with the statistical properties and correlations of matter-wave fields. A first step in this area is the measurement of reduced number fluctuations in a Bose-Einstein condensate partitioned into a series of optical potential wells.

Journal Article↗
PubMed2002

Photoassociation of sodium in a Bose-Einstein condensate.

We form ultracold Na2 molecules by single-photon photoassociation of a Bose-Einstein condensate, measuring the photoassociation rate, linewidth, and light shift of the J = 1, v = 135 vibrational level of the A1 Sigma (+)(u) molecular state. The photoassociation rate constant increases linearly with intensity, even where it is predicted that many-body effects might limit the rate. Our observations are in good agreement with a two-body theory having no free parameters.

Journal Article↗
PubMed2001

Dynamical tunnelling of ultracold atoms.

The divergence of quantum and classical descriptions of particle motion is clearly apparent in quantum tunnelling between two regions of classically stable motion. An archetype of such non-classical motion is tunnelling through an energy barrier. In the 1980s, a new process, 'dynamical' tunnelling, was predicted, involving no potential energy barrier; however, a constant of the motion (other than energy) still forbids classically the quantum-allowed motion. This process should occur, for example, in periodically driven, nonlinear hamiltonian systems with one degree of freedom. Such systems may be chaotic, consisting of regions in phase space of stable, regular motion embedded in a sea of chaos. Previous studies predicted dynamical tunnelling between these stable regions. Here we observe dynamical tunnelling of ultracold atoms from a Bose-Einstein condensate in an amplitude-modulated optical standing wave. Atoms coherently tunnel back and forth between their initial state of oscillatory motion (corresponding to an island of regular motion) and the state oscillating 180 degrees out of phase with the initial state.

Journal Article↗
PubMed2001

Spatial distribution and developmental appearance of postjunctional P2X1 receptors on smooth muscle cells of the mouse vas deferens.

P2X1-type purinoceptors have been shown to mediate fast transmission between sympathetic varicosities and smooth muscle cells in the mouse vas deferens but the spatial organization of these receptors on the smooth muscle cells remains inconclusive. Voltage clamp techniques were used to estimate the amplitudes of spontaneous excitatory junction currents (SEJCs) in cells of the vas deferens longitudinal smooth muscle layer. These currents involved the activation of about 6% of the P2X-type channels present on the cell, as compared to whole cell currents produced when isolated smooth muscle cells were exposed to maximal concentrations of either ATP or alpha,beta-MeATP. Immunofluorescence staining of the vas deferens with antibodies against P2X1 receptor showed a diffuse, grainy distribution over the entire membrane of each smooth muscle cell. Anti-P2X1 staining was not markedly clustered beneath anti-SV2-stained sympathetic varicosities. Similar results were obtained for cells in the urinary bladder. During development, P2X1 mRNA was detected as early as embryonic day 15 (E15). Increasing intensities of diffuse immunostaining for P2X1 were observed in the walls of the bladder, tail artery, and aorta from E15 until 6 weeks postnatal. The vas deferens showed increasing intensities of diffuse staining of its smooth muscle layers between 2 and 6 weeks postnatal, consistent with the time-course of development of fast purinergic transmission described previously. Together, the results suggest that the response of smooth muscle of the vas deferens to ATP released from sympathetic varicosities relies on rapidly desensitizing P2X1 receptors, distributed diffusely across the smooth muscle cell surface.

Adenosine Triphosphate↗
PubMed2001

Structure and chromosome location of the mouse P2X(1) purinoceptor gene (P2rx1).

P2X(1) receptors are ATP-gated cation channels that mediate the fast, purinergic component of sympathetic nerve-smooth muscle neurotransmission in the mouse vas deferens and may serve comparable functions in the urinary bladder and the arteries. The gene for mouse P2X(1) (P2rx1) was cloned and its genomic structure defined by sequencing. The gene spans about 10 kb and consists of 12 exons. All splice sites conformed to the GT-AG motif and the exon-intron boundaries were largely conserved with other members of the P2X gene family so far cloned. A single transcription-starting site was identified by 5' RACE analysis, 233 bp upstream of the translation start site. The P2X(1) gene maps to the central region of mouse chromosome 11.

Animals↗
PubMed2000

Development of fast purinergic transmission in the mouse vas deferens.

ATP released by sympathetic varicosities of the mouse vas deferens binds to P2X receptors which activate fast, ligand-gated channels, resulting in depolarisation of smooth muscle cells. We examined the development of fast neuromuscular transmission at surface longitudinal smooth muscle fibres of the mouse vas deferens. Sympathetic varicosities were visualised using DiOC(2)(5)-fluorescence to aid in positioning loose patch electrodes over small sets of sympathetic varicosities to record the nerve terminal impulse (NTI) and excitatory junction currents (EJCs) evoked during nerve stimulation. At the earliest age at which EJCs could be detected, 21 days postnatal (PN), most recording sites rarely showed a detectable EJC over 100 trials, even though NTIs were recorded without failure. The extent of such intermittence in transmitter release progressively declined between 21 and 42 days PN. In addition, the mean amplitude of spontaneous EJCs (SEJCs) and EJCs increased by 2- and 2.4-fold, respectively, between 21 and 42 days PN. The rise time of EJCs varied widely at each age but declined with development (e.g., 7-14 ms at 28 days PN, 3-12 ms at 42 days PN). All EJCs were abolished by suramin (100 microM). Fast rise time EJCs were rapidly abolished by alpha,beta-methylene ATP (20 microM) while some (34%) of the slower rise time EJCs were resistant to rapid desensitisation of this kind. P2X(1) and P2X(2) mRNAs were detected by reverse transcription and polymerase chain reaction (RT-PCR) to determine whether levels of expression of the receptor subunits might explain the increased EJC amplitude. Between 10 and 42 days PN no marked change was observed in the P2X(2) receptor mRNA or beta-actin mRNA (control). In contrast, the intensity of the RT-PCR band for P2X(1) receptor showed a progressive approximately 4.3-fold developmental increase relative to the P2X(2) band. These observations suggest that both prejunctional and postjunctional mechanisms cause the maturation of fast purinergic junctional transmission at the longitudinal muscle of the mouse vas deferens between 21 and 42 days PN.

Adenosine Triphosphate↗
PubMed2000

Overexpression of rapsyn modifies the intracellular trafficking of acetylcholine receptors.

Rapsyn is a protein that interacts with the cytoplasmic face of the nicotinic acetylcholine receptors (AChR) to cluster them within postsynaptic membrane of muscle. Here we show that intracellular AChRs are also affected by rapsyn. When rapsyn was co-transfected with AChR into QT-6 fibroblasts, (125)I-alpha-bungarotoxin binding indicated a reduction in the fraction of AChRs expressed on the cell surface, compared to cells expressing AChRs alone. Double fluorescent labeling showed that intracellular AChRs accumulated in patches at the cell periphery, beneath rapsyn-associated cell surface AChR clusters. These patches were observed even when cells were grown in medium containing excess unlabelled alpha-bungarotoxin to mask internalized AChRs, suggesting that they arose from hindered trafficking of newly formed AChRs to the cell surface. Similarly, in the muscle cell line, C2, overexpression of rapsyn resulted in the co-localization of aggregates of intracellular alpha-bungarotoxin binding sites with rapsyn beneath cell surface AChR microaggregates. The results indicate that rapsyn can modify the trafficking of AChRs within the cell and suggest a role in selectively targeting newly synthesized intracellular AChRs to the postsynaptic membrane.

Animals↗
PubMed1999

Expression and localisation of dynamin and syntaxin during neural development and neuromuscular synapse formation.

The expression and subcellular localisation of dynamin and syntaxin were examined during the periods of motor neuron development and neuromuscular synaptogenesis in the mouse embryo. Both dynamin and syntaxin could be detected by immunoblotting in the spinal cord at embryonic day 10 (E10; 2 days before axon outgrowth) and at all subsequent ages examined. Reverse transcription and polymerase chain reaction (RT-PCR) identified low levels of all three carboxy-terminal splicing forms of dynamin I in spinal cord from as early as E10. During the period of maturation of spinal neurons, from E10 to the first postnatal day (P0), the short carboxy-terminal splicing form of dynamin I (dynamin I*b) was up-regulated, as was dynamin III, relative to dynamin II mRNA. Syntaxin immunostaining became colocalized with the synaptic vesicle protein, SV2, at neuromuscular synapses within 12 hours of the commencement of synapse formation and throughout subsequent development. In contrast, dynamin, which is important for activity-dependent synaptic vesicle recycling and, thus, sustained neurotransmission, could not be detected at most newly formed synapses until several days after synapse formation. The delayed appearance of dynamin at the synapse, thus, heralds the neonatal development of robust synaptic transmission at the neuromuscular junction.

Animals↗
PubMed1999

Overexpression of rapsyn inhibits agrin-induced acetylcholine receptor clustering in muscle cells.

Rapsyn is a protein on the cytoplasmic face of the postsynaptic membrane of skeletal muscle that is essential for clustering acetylcholine receptors (AChR). Here we show that transfection of rapsyn cDNA can restore AChR clustering function to muscle cells cultured from rapsyn deficient (KORAP) mice. KORAP myotubes displayed no AChR aggregates before or after treatment with neural agrin. After transfection with rapsyn expression plasmid, some KORAP myotubes expressed rapsyn at physiological levels. These formed large AChR-rapsyn clusters in response to agrin, just like wild-type myotubes. KORAP myotubes that overexpressed rapsyn formed only scattered AChR-rapsyn microaggregates, irrespective of agrin treatment. KORAP cells were then transfected with mutant forms of rapsyn. A deletion mutant lacking residues 16-254 formed rapsyn microaggregates, but failed to aggregate AChRs. Substitution mutation to the C-terminal serine phosphorylation site of rapsyn (M43(D405,D406)) did not impair the response to agrin, showing that differential phosphorylation of this site is unlikely to mediate agrin-induced clustering. The results indicate that rapsyn expression is essential for agrin-induced AChR clustering but that its overexpression inhibits this pathway. The approach of using rapsyn-deficient muscle cells opens the way for defining the role of rapsyn in agrin-induced AChR clustering.

Agrin↗
PubMed1997

A microcosm study on remediation of explosives-contaminated groundwater using constructed wetlands.

Anaerobic degradation of TNT and TNB in gravel systems was rapid and similar to removal rates in parrot feather lagoons. Planted and unplanted anaerobic gravel systems were the only treatments that provided significant reduction of RDX and HMX. Planted systems with parrot feather had no effect on removal rates of explosives in anaerobic gravel systems. Reciprocating wetlands were not effective in biodegrading RDX or HMX, but were very efficient at removing COD. A scaled-up concept for bioremediating contaminated groundwater can be envisioned with the data obtained in the current study. The effectiveness of anaerobic gravel systems indicate an anaerobic subsurface-flow constructed wetland can be established as the primary treatment for remediation with C added to the influent or step fed down the length of the wetland. Another option would be to add compost as a more permanent source of C to the gravel substrate. With time, the need for C supplementation may be reduced with the C exudates and redox lowering potential of certain plants like canarygrass (Phalaris arundinacea). As a secondary treatment, a reciprocating wetland would appear to be a logical choice to quickly remove C released in effluent waters of the anaerobic wetland.

Animals↗
PubMed1997

Clustering of GABAA receptors by rapsyn/43kD protein in vitro.

Rapsyn, a 43-kDa protein on the cytoplasmic face of the postsynaptic membrane, is essential for clustering acetylcholine receptors (AChR) at the neuromuscular junction. When transfected into nonmuscle cells (QT-6), rapsyn forms discrete membrane domains and can cluster AChR into these same domains. Here we examined whether rapsyn can cluster other ion channels as well. When expressed in QT-6 cells, the GABAA receptor (human alpha 1, beta 1, and gamma 2 subunits) and the skeletal muscle sodium channel were each diffusely scattered across the cell surface. Rapsyn, when co-expressed, clustered the GABAA receptor as effectively as it clustered AChR in previous studies. Rapsyn did not cluster co-transfected sodium channel, confirming that it does not cluster ion channels indiscriminately. Rapsyn mRNA was detected at low levels in the brain by polymerase chain reaction amplification of reverse-transcribed RNA, raising the possibility of a broader role for rapsyn.

Animals↗
PubMed1997

Rapsyn and agrin slow the metabolic degradation of the acetylcholine receptor.

Rapsyn is a 43-kDa cytoplasmic protein that clusters nicotinic acetylcholine receptors (AChR) in the postsynaptic membrane. Here we examine the effect of rapsynmediated AChR clustering on the metabolic stability of the AChR. When transfected into QT-6 fibroblasts, cell surface AChRs (alpha, beta, epsilon, and delta subunit combination) pulse labeled with 125I-alpha-bungarotoxin were degraded with a half-life of 16.4 +/- 1.1 h (mean +/- SEM). Cotransfection of rapsyn with AChR caused extensive AChR clustering and increased AChR half-life to 20.5 +/- 1.0 h. Anti-AChR antibodies such as mab 35 cause an increased AChR degradation often associated with myasthenia gravis: 80.8 +/- 2.5% of AChRs labeled at zero time were degraded over a 12-h period. Contransfection of rapsyn reduced this AChR loss to 66.4 +/- 3.8%. Rapsyn also reduced normal AChR degradation, from 53.2 +/- 2.1 to 44.2 +/- 2.2%. Muscle cell lines from wild-type myotubes displayed few AChR clusters, but treatment with neural agrin increased the number of AChR clusters 30-fold. Clustering was accompanied by reductions in AChR degradation (both in the presence and absence of mab 35) similar in magnitude to those produced by overexpression of rapsyn in QT-6 cells. In rapsyn-deficient myotubes, treatment with neural agrin neither caused AChR clustering nor reduced AChR degradation. Thus neural agrin may slow AChR degradation by inducing the rapsyn-dependent clustering of AChRs.

Agrin↗
PubMed1996

Optically controlled collisions of biological objects to evaluate potent polyvalent inhibitors of virus-cell adhesion.

BACKGROUND: The biochemical and biomechanical determinants of adhesion between two biological objects following a collision are complex, and may vary from one system to another. We wished to develop an assay in which all the relevant factors, including the components of the solution, the relative orientation and the relative collision velocity, are under the user's control. RESULTS: A new assay is described in which two mesoscale particles are caused to collide using two independently controlled optical tweezers (optically controlled collision, OPTCOL). This assay enables precise examination of the probability of adhesion under biologically relevant conditions. The OPTCOL assay was used to evaluate the probability of adhesion of a single erythrocyte to a single virus-coated microsphere, in the absence and presence of a sialic acidbearing inhibitor. Inhibition constants for the most effective inhibitors could not be measured using other types of assays. The best inhibitor prevented attachment 50 % of the time at a sialic acid concentration of 35 pmol l-1; it is the most potent known inhibitor of attachment of influenza virus to erythrocytes. CONCLUSIONS: OPTCOL is a versatile new bioassay for studying dynamic interactions in biochemistry. It offers an approach to investigating interactions between moving biological objects that is both quantitative and interpretable. The simplicity of the OPTCOL technique suggests broad applicability to the study of adhesion of mesoscale (1-100 microm) objects in the areas of cell biology, microbiology, medicinal chemistry, and biophysics.

Cell Adhesion↗
PubMed1996

Sensitivity to the frequency of parts and kinds: two principles of organisation in semantic memory.

Are subjects sensitive to the frequency of parts of the same whole in the same way that they are sensitive to instances of the same category? Subjects read a randomised list of words and then estimated how many words on the list had belonged to particular groups, e.g. parts of a bird, or kinds of bird. Groups of words were either parts of the same whole, e.g. feathers, beak, wing, or members of the same category, e.g. robin, sparrow, eagle. Subjects were asked, either, "How many parts of a (bird) did you see?" or "How many kinds of (bird) did you see?". Half of the subjects expected the frequency estimation task, whereas for the other half, who performed a distractor task during encoding, the task was unexpected. In Experiment 1 subjects saw either parts of kinds. Sensitivity to frequency did not differ for parts and kinds nor as a function of whether the frequency estimation test was expected. In Experiment 2 subjects saw both parts and kinds belonging to the same superordinates, e.g. parts of birds and kinds of birds, and were asked to estimate the frequency of both types of groupings for each superordinate. The results were the same as in Experiment 1. In addition, subjects were able to separate the frequency of parts and kinds of the same superordinate. The results suggest that, in frequency estimation, part-of and kind-of associations can function similarly, and that the mechanism responsible for frequency estimation is sensitive to the type of association.

Humans↗
PubMed1995

Microlithography by using neutral metastable atoms and self-assembled monolayers.

Lithography can be performed with beams of neutral atoms in metastable excited states to pattern self-assembled monolayers (SAMs) of alkanethiolates on gold. An estimated exposure of a SAM of dodecanethiolate (DDT) to 15 to 20 metastable argon atoms per DDT molecule damaged the SAM sufficiently to allow penetration of an aqueous solution of ferricyanide to the surface of the gold. This solution etched the gold and transformed the patterns in the SAMs into structures of gold; these structures had edge resolution of less than 100 nanometers. Regions of SAMs as large as 2 square centimeters were patterned by exposure to a beam of metastable argon atoms. These observations suggest that this system may be useful in new forms of micro- and nanolithography.

Argon↗