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Biomedical subjects

W Ho

Publications and source records attributed to W Ho.

At least 19 recordsLinked to original sources
PubMed2003

Visualization and spectroscopy of a metal-molecule-metal bridge.

Artificial nanostructures, each composed of a copper(II) phthalocyanine (CuPc) molecule bonded to two gold atomic chains with a controlled gap, were assembled on a NiAl(110) surface by manipulation of individual gold atoms and CuPc molecules with a scanning tunneling microscope. The electronic densities of states of these hybrid structures were measured by spatially resolved electronic spectroscopy and systematically tuned by varying the number of gold atoms in the chains one by one. The present approach provides structural images and electronic characterization of the metal-molecule-metal junction, thereby elucidating the nature of the contacts between the molecule and metal in this junction.

Journal Article↗
PubMed2003

Atomic engineering of photon emission with a scanning tunneling microscope.

We present measurements of photon emission from individual several-atom silver chains on the NiAl(110) surface, excited by tunneling electrons in a scanning tunneling microscope (STM). The chains were assembled by manipulating single silver atoms on the NiAl(110) surface with the STM. The photon energy of this emission can be tuned by appending a single atom to the chain. These changes in photon emission result from changes in the electronic structure of the silver chain, each electronic state inside the chain being associated with a distinct channel of emission.

Journal Article↗
PubMed2003

Distance dependence of the interaction between single atoms: gold dimers on NiAl(110).

The importance of substrate-mediated adsorbate-adsorbate interactions on electronic states has been demonstrated for Au dimers on NiAl(110) with a scanning tunneling microscope and density functional calculations. An unoccupied resonance observed in single Au atoms splits into a doublet in Au dimers. The energy splitting depends inversely on the distance between the two adatoms, revealing the relative importance of direct and substrate-mediated interactions. Spatially resolved conductance measurements of Au dimers reveal the symmetric and antisymmetric characters of the doublet states.

Journal Article↗
PubMed2003

Localized molecular constraint on electron delocalization in a metallic chain.

An artificial quantum structure consisting of a single CO molecule adsorbed on a Au chain was assembled by manipulating single Au atoms on NiAl(110) at 12 K with a scanning tunneling microscope (STM). The CO disrupts the delocalization of electron density waves in the chain, as it suppresses the coupling between neighboring chain atoms. The possibility to specify the CO position on the chain allows controlled modification of the electronic properties in a quantum system. Inelastic electron tunneling spectroscopy with the STM provides vibrational characterization of the adsorbed CO.

Journal Article↗
PubMed2003

Influence of a heterogeneous Al2O3 surface on the electronic properties of single Pd atoms.

Electronic properties of single Pd atoms, deposited on Al(2)O(3)/NiAl(110), have been characterized by scanning tunneling spectroscopy at 12 K. The spectra reveal distinct conductivity resonances, assigned to discrete electronic levels in the atom. The energy position of the resonances reflects adsorption properties of Pd atoms on different sites of the oxide support. Mapping the spatial extent of conductivity channels in the Pd atoms yields the symmetry of the underlying electronic states. The results demonstrate the effect of a heterogeneous oxide surface on the electronic structure of adsorbed metal atoms.

Journal Article↗
PubMed2003

Vibrationally resolved fluorescence excited with submolecular precision.

Tunneling electrons from a scanning tunneling microscope (STM) were used to excite photon emission from individual porphyrin molecules adsorbed on an ultrathin alumina film grown on a NiAl(110) surface. Vibrational features were observed in the light-emission spectra that depended sensitively on the different molecular conformations and corresponding electronic states obtained by scanning tunneling spectroscopy. The high spatial resolution of the STM enabled the demonstration of variations in light-emission spectra from different parts of the molecule. These experiments realize the feasibility of fluorescence spectroscopy with the STM and enable the integration of optical spectroscopy with a nanoprobe for the investigation of single molecules.

Journal Article↗
PubMed2003

Antineuronal antibodies in idiopathic achalasia and gastro-oesophageal reflux disease.

BACKGROUND AND AIMS: The precise aetiology of achalasia is unknown although autoimmunity has been implicated and is supported by several studies. We screened sera from patients with achalasia or gastro-oesophageal reflux disease (GORD) to test for circulating antimyenteric neuronal antibodies. METHODS: Serum was obtained from 45 individuals with achalasia, 16 with GORD, and 22 normal controls. Serum was used in immunohistochemistry to label whole mount preparations of ileum and oesophagus of the guinea pig and mouse. Also, sections of superior cervical and dorsal root ganglia, and spinal cord were examined. RESULTS: Positive immunostaining of the myenteric plexus was detected in significantly more achalasia and GORD samples than control samples (achalasia, p<0.001; GORD, p<0.01), and immunoreactivity was significantly more intense with achalasia and GORD serum samples than controls (achalasia, p<0.01; GORD, p<0.05). There was no correlation between intensity of immunoreactivity and duration of achalasia symptoms. In most cases, achalasia and GORD sera stained all ileal submucosal and myenteric neurones, and oesophageal neurones. Immunostaining was not species specific; however, immunostaining was largely specific for enteric neurones. Western blot analysis failed to reveal specific myenteric neuronal proteins that were labelled by antibodies in achalasia or GORD serum. CONCLUSIONS: These data suggest that antineuronal antibodies are generated in response to tissue damage or some other secondary phenomenon in achalasia and GORD. We conclude that antineuronal antibodies found in the serum of patients with achalasia represent an epiphenomenon and not a causative factor.

Animals↗
PubMed2002

Electronic density oscillations in gold atomic chains assembled atom by atom.

Linear Au chains two to 20 atoms long were constructed on a NiAl(110) surface via the manipulation of single atoms with a scanning tunneling microscope. Differential conductance (dI/dV) images of these chains reveal one-dimensional electronic density oscillations at energies 1.0 to 2.5 eV above the Fermi energy. The origin of this delocalized electronic structure is traced to the existence of an electronic resonance measured on single, isolated Au atoms. Variations in the wavelength in dI/dV images of an eleven-atom chain taken at different energies revealed an effective electronic mass of 0.4+/-0.1 times the mass of a free-electron.

Journal Article↗
PubMed2002

Development of one-dimensional band structure in artificial gold chains.

The ability of a scanning tunneling microscope to manipulate single atoms is used to build well-defined gold chains on NiAl(110). The electronic properties of the one-dimensional chains are dominated by an unoccupied electron band, gradually developing from a single atomic orbital present in a gold atom. Spatially resolved conductance measurements along a 20-atom chain provide the dispersion relation, effective mass, and density of states of the free electron-like band. These experiments demonstrate a strategy for probing the interrelation between geometric structure, elemental composition, and electronic properties in metallic nanostructures.

Journal Article↗
PubMed2002

Kindling induces the mRNA expression of methyl DNA-binding factors in the adult rat hippocampus.

We have investigated the gene expression responses of a family of methyl CpG-binding domain-containing factors (MeCP2, MBD1, MBD2, and MBD3) in the hippocampus of electrically kindled rats. Expression was examined in both amygdala- and partial perforant-pathway-kindled subjects, 24 h and 28 days following the final stimulation. In general, the responses of MBDs 2 and 3 paralleled each another, both temporally and spatially. The expression of both genes was significantly elevated in all hippocampal subfields at 24 h following either the fifth stage 5 seizure (amygdala kindling) or the 15th stimulation of the perforant pathway. This induced expression was transient, however, as the expression of both genes returned to control levels by 28 days. This pattern of response contrasted to that observed for MeCP2 and MBD1. MeCP2 displayed no change in expression either 24 h or 28 days after amygdala kindling, but did display a late-developing, significant increase in expression in the dentate gyrus at 28 days following perforant-pathway kindling. The expression of MBD1 was unchanged by partial perforant-pathway kindling, but was induced in the dentate gyrus 28 days after amygdala kindling. These results demonstrate that electrical kindling alters the hippocampal expression of methyl DNA-binding factors, but does not affect each factor equivalently. The responsive patterns observed suggest that this family of transcriptional regulators can be differentially altered in the hippocampus by seizure activity.

Amygdala↗
PubMed2002

Transient forebrain ischemia alters the mRNA expression of methyl DNA-binding factors in the adult rat hippocampus.

We have examined how transient cerebral ischemia affects the mRNA expression of a family of methyl CpG-binding domain (MBD)-containing factors in the rat hippocampus. Our results show that each member of this family is affected by cerebral ischemia challenge, but with differing patterns of responsiveness. At 3, 6 and 12 h following reperfusion, MeCP2 and MBD1 expression is maintained at control levels throughout the hippocampus. At 24 h, MeCP2 and MBD1 are induced in both the CA1 and CA3 subfields. This delayed pattern of induction is in contrast to the responses of MBD2 and MBD3. Both MBD2 and MBD3 display significant changes in expression at early times following reperfusion, although their changes are opposite in direction. MBD2 expression is induced throughout the hippocampal formation at 6 h, and remains elevated at 12 and 24 h. MBD3 expression decreases as early as 3 h following insult in the CA3 and dentate gyrus, and the decreased expression remains in the vulnerable CA1 subfield at 6, 12, and 24 h. Taken together, these results are the first to illustrate that the expression of methyl DNA-binding factors are affected by challenges to the brain, and they also illustrate that each methyl DNA-binding factor responds differently to cerebral ischemic challenge. As each of these family members is associated either directly or indirectly with the inhibition of gene transcription, our results suggest that following cerebral ischemia the normal pattern of transcriptional inhibition provided by these factors may be altered in the hippocampus.

Age Factors↗
PubMed2001

Crystal structure of a ternary SAP-1/SRF/c-fos SRE DNA complex.

Combinatorial DNA binding by proteins for promoter-specific gene activation is a common mode of DNA regulation in eukaryotic organisms, and occurs at the promoter of the c-fos proto-oncogene. The c-fos promoter contains a serum response element (SRE) that mediates ternary complex formation with the Ets proteins SAP-1 or Elk-1 and the MADS-box protein, serum response factor (SRF). Here, we report the crystal structure of a ternary SAP-1/SRF/c-fos SRE DNA complex containing the minimal DNA-binding domains of each protein. The structure of the complex reveals that the SAP-1 monomer and SRF dimer are bound on opposite faces of the DNA, and that the DNA recognition helix of SAP-1 makes direct contact with the DNA recognition helix of one of the two SRF subunits. These interactions facilitate an 82 degrees DNA bend around SRF and a modulation of protein-DNA contacts by each protein when compared to each of the binary DNA complexes. A comparison with a recently determined complex containing SRF, an idealized DNA site, and a SAP-1 fragment containing a SRF-interacting B-box region, shows a similar overall architecture but also shows important differences. Specifically, the comparison suggests that the B-box region of the Ets protein does not significantly influence DNA recognition by either of the proteins, and that the sequence of the DNA target effects the way in which the two proteins cooperate for DNA recognition. These studies have implications for how DNA-bound SRF may modulate the DNA-binding properties of other Ets proteins such as Elk-1, and for how other Ets proteins may modulate the DNA-binding properties of other DNA-bound accessory factors to facilitate promoter-specific transcriptional responses.

Amino Acid Sequence↗
PubMed2001

Single molecule imaging and vibrational spectroscopy with a chemically modified tip of a scanning tunneling microscope.

The tip of a scanning tunneling microscope can be chemically modified by transferring a single molecule from the surface. Such a molecule-terminated tip yields enhanced resolution in topographical imaging of substrate atoms and molecular orbitals of molecules adsorbed on the surface. In addition, vibrational modes are detected in single molecule inelastic electron tunneling spectroscopy which are not observed with a bare tip. These new findings are revealed by transferring a carbon monoxide or an ethylene molecule to the tip and probing single carbon monoxide and oxygen molecules adsorbed on Ag(110) at 13 K.

Journal Article↗
PubMed2001

Single-molecule vibrations, conformational changes, and electronic conductivity of five-membered heterocycles.

Using an ultrahigh vacuum scanning tunneling microscope (STM), we have explored the interactions of isolated five-membered heterocycles, pyrrole, thiophene, pyrrolidine, and tetrahydrothiophene, with the Cu(001) surface at 9 K. Pyrrolidine was also studied on the Ag(001) surface. Important distinctions in bonding, vibrational spectra, and vibrationally mediated negative differential resistance were observed with the aid of single-molecule inelastic electron tunneling spectroscopy (STM-IETS).

Journal Article↗
PubMed2001

Oxidation of a single carbon monoxide molecule manipulated and induced with a scanning tunneling microscope.

A carbon monoxide molecule (CO) was positioned with a scanning tunneling microscope (STM) at various distances from an oxygen atom (O) on the Ag(110) surface at 13 K. At the closest separation, carbon dioxide (CO(2)) production was induced by tunneling electrons. Direct reaction of a CO desorbed from the STM tip with an O atom on Ag(110) illustrates another catalytic oxidation mechanism. Inelastic electron tunneling spectroscopy with the STM was used to monitor the vibrations of CO in its different environment.

Journal Article↗
PubMed2001

Somatostatin type 2 receptor expression in the rat hippocampus following cerebral ischemia.

We examined how transient cerebral ischemia affects the mRNA expression, and the immunoreactive distribution, of the somatostatin type 2 (sst2) receptor in the adult rat hippocampus. Following reperfusion, sst2 mRNA levels increased significantly in the CA1 region by 3 h, and were also increased in the CA3 and CA4/hilus subfields at 6 and 12 h. At 24 h, however, sst2 receptor mRNA levels returned to baseline throughout the hippocampus. At the protein level, we found the regional immunoreactivity of the sst2a receptor was maintained, or slightly elevated, throughout the hippocampus at 6 h, but not different from control at 24 h. These results suggest that sst2 receptors maintain their normal distribution and prevalence in the post-ischemic hippocampus before the deterioration of the vulnerable CA1 neurons. Thus, they represent attractive targets for neuroprotective interventions.

Animals↗
PubMed2001

Perforant pathway kindling transiently induces the mRNA expression of GABA-B receptor subtypes R1A and R2 in the adult rat hippocampus.

We examined the gene expression responses of GABA-B R1A, R1B and R2 receptor subtypes in the hippocampus of perforant pathway-kindled rats at 24 h and 28 days after 15 consecutive daily stimulations. We found R1A expression, but not R1B expression, to be significantly induced in the dentate gyrus at 24 h. No change in the expression of R1A or R1B was observed at 28 days. R2 expression was induced throughout the hippocampus at 24 h, but also returned to control levels by 28 days. Thus, our results show that kindling induces a transient increase in GABA-B receptor mRNA in the hippocampus.

Age Factors↗