579 research outputs found
Clinical features of a novel TIMP-3 mutation causing Sorsby's fundus dystrophy: implications for disease mechanism
AIMS: To describe the phenotype in three family members affected by a novel mutation in the gene coding for the enzyme tissue inhibitor of metalloproteinase-3 (TIMP-3).
METHODS: Three members of the same family were seen with a history of nyctalopia and visual loss due to maculopathy. Clinical features were consistent with Sorsby's fundus dystrophy. Exon 5 of the gene coding for TIMP-3 was amplified by the polymerase chain reaction, single strand conformation polymorphism analysis undertaken and exon 5 amplicons were directly sequenced.
RESULTS: Onset of symptoms was in the third to fourth decade. Five of six eyes had geographic macular atrophy rather than neovascularisation as a cause for central visual loss. Peripheral retinal pigmentary disturbances were present. Scotopic ERGs were abnormal in all three. Mutation analysis showed a GT transversion in all three resulting in a premature termination codon, E139X, deleting most of the carboxy terminal domain of TIMP-3.
CONCLUSIONS: The patients described had a form of Sorsby's fundus dystrophy which fell at the severe end of the spectrum of this disease. Postulated disease mechanisms include deposition of dimerised TIMP-3 protein
The pharmacokinetics of medetomidine administered subcutaneously during Isoflurane anaesthesia in Sprague-Dawley rats
Anaesthetic protocols involving the combined use of a sedative agent, medetomidine, and an anaesthetic agent, isoflurane, are increasingly being used in functional magnetic resonance imaging (fMRI) studies of the rodent brain. Despite the popularity of this combination, a standardised protocol for the combined use of medetomidine and isoflurane has not been established, resulting in inconsistencies in the reported use of these drugs. This study investigated the pharmacokinetic detail required to standardise the use of medetomidine and isoflurane in rat brain fMRI studies. Using mass spectrometry, serum concentrations of medetomidine were determined in Sprague-Dawley rats during medetomidine and isoflurane anaesthesia. The serum concentration of medetomidine for administration with 0.5% (vapouriser setting) isoflurane was found to be 14.4 ng/mL (±3.0 ng/mL). The data suggests that a steady state serum concentration of medetomidine when administered with 0.5% (vapouriser setting) isoflurane can be achieved with an initial subcutaneous (SC) dose of 0.12 mg/kg of medetomidine followed by a 0.08 mg/kg/h SC infusion of medetomidine. Consideration of these results for future studies will facilitate standardisation of medetomidine and isoflurane anaesthetic protocols during fMRI data acquisition
Electromigration-Induced Flow of Islands and Voids on the Cu(001) Surface
Electromigration-induced flow of islands and voids on the Cu(001) surface is
studied at the atomic scale. The basic drift mechanisms are identified using a
complete set of energy barriers for adatom hopping on the Cu(001) surface,
combined with kinetic Monte Carlo simulations. The energy barriers are
calculated by the embedded atom method, and parameterized using a simple model.
The dependence of the flow on the temperature, the size of the clusters, and
the strength of the applied field is obtained. For both islands and voids it is
found that edge diffusion is the dominant mass-transport mechanism. The rate
limiting steps are identified. For both islands and voids they involve
detachment of atoms from corners into the adjacent edge. The energy barriers
for these moves are found to be in good agreement with the activation energy
for island/void drift obtained from Arrhenius analysis of the simulation
results. The relevance of the results to other FCC(001) metal surfaces and
their experimental implications are discussed.Comment: 9 pages, 13 ps figure
Numerical analysis of the radio-frequency single-electron transistor operation
We have analyzed numerically the response and noise-limited charge
sensitivity of a radio-frequency single-electron transistor (RF-SET) in a
non-superconducting state using the orthodox theory. In particular, we have
studied the performance dependence on the quality factor Q of the tank circuit
for Q both below and above the value corresponding to the impedance matching
between the coaxial cable and SET.Comment: 14 page
CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic fibrosis disease severity
BACKGROUND: Cystic fibrosis (CF) lung disease manifest by impaired chloride secretion leads to eventual respiratory failure. Candidate genes that may modify CF lung disease severity include alternative chloride channels. The objectives of this study are to identify single nucleotide polymorphisms (SNPs) in the airway epithelial chloride channel, CLC-2, and correlate these polymorphisms with CF lung disease. METHODS: The CLC-2 promoter, intron 1 and exon 20 were examined for SNPs in adult CF dF508/dF508 homozygotes with mild and severe lung disease (forced expiratory volume at one second (FEV1) > 70% and < 40%). RESULTS: PCR amplification of genomic CLC-2 and sequence analysis revealed 1 polymorphism in the hClC -2 promoter, 4 in intron 1, and none in exon 20. Fisher's analysis within this data set, did not demonstrate a significant relationship between the severity of lung disease and SNPs in the CLC-2 gene. CONCLUSIONS: CLC-2 is not a key modifier gene of CF lung phenotype. Further studies evaluating other phenotypes associated with CF may be useful in the future to assess the ability of CLC-2 to modify CF disease severity
Comparison of behavioral and clinical effects of intravenous amitraz or romifidine administration in horses
A measurement of the tau mass and the first CPT test with tau leptons
We measure the mass of the tau lepton to be 1775.1+-1.6(stat)+-1.0(syst.) MeV
using tau pairs from Z0 decays. To test CPT invariance we compare the masses of
the positively and negatively charged tau leptons. The relative mass difference
is found to be smaller than 3.0 10^-3 at the 90% confidence level.Comment: 10 pages, 4 figures, Submitted to Phys. Letts.
Measurement of the B0 Lifetime and Oscillation Frequency using B0->D*+l-v decays
The lifetime and oscillation frequency of the B0 meson has been measured
using B0->D*+l-v decays recorded on the Z0 peak with the OPAL detector at LEP.
The D*+ -> D0pi+ decays were reconstructed using an inclusive technique and the
production flavour of the B0 mesons was determined using a combination of tags
from the rest of the event. The results t_B0 = 1.541 +- 0.028 +- 0.023 ps, Dm_d
= 0.497 +- 0.024 +- 0.025 ps-1 were obtained, where in each case the first
error is statistical and the second systematic.Comment: 17 pages, 4 figures, submitted to Phys. Lett.
First Measurement of Z/gamma* Production in Compton Scattering of Quasi-real Photons
We report the first observation of Z/gamma* production in Compton scattering
of quasi-real photons. This is a subprocess of the reaction e+e- to
e+e-Z/gamma*, where one of the final state electrons is undetected.
Approximately 55 pb-1 of data collected in the year 1997 at an e+e-
centre-of-mass energy of 183 GeV with the OPAL detector at LEP have been
analysed. The Z/gamma* from Compton scattering has been detected in the
hadronic decay channel. Within well defined kinematic bounds, we measure the
product of cross-section and Z/gamma* branching ratio to hadrons to be
(0.9+-0.3+-0.1) pb for events with a hadronic mass larger than 60 GeV,
dominated by (e)eZ production. In the hadronic mass region between 5 GeV and 60
GeV, dominated by (e)egamma* production, this product is found to be
(4.1+-1.6+-0.6) pb. Our results agree with the predictions of two Monte Carlo
event generators, grc4f and PYTHIA.Comment: 18 pages, LaTeX, 5 eps figures included, submitted to Physics Letters
WW Production Cross Section and W Branching Fractions in e+e- Collisions at 189 GeV
From a data sample of 183 pb^-1 recorded at a center-of-mass energy of roots
= 189 GeV with the OPAL detector at LEP, 3068 W-pair candidate events are
selected. Assuming Standard Model W boson decay branching fractions, the W-pair
production cross section is measured to be sigmaWW = 16.30 +- 0.34(stat.) +-
0.18(syst.) pb. When combined with previous OPAL measurements, the W boson
branching fraction to hadrons is determined to be 68.32 +- 0.61(stat.) +-
0.28(syst.) % assuming lepton universality. These results are consistent with
Standard Model expectations.Comment: 22 pages, 5 figures, submitted to Phys. Lett.
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