2,394 research outputs found
Tetrahydrobiopterin analogues with NO-dependent pulmonary vasodilator properties
Reduced NO levels due to the deficiency of tetrahydrobiopterin (BH4) contribute to impaired vasodilation in pulmonary hypertension Due to the chemically unstable nature of BH4 it was hypothesised that oxidatively stable analogues of BR, would be able to support NO synthesis to improve Endothelial dysfunction in pulmonary hypertension Two analogues of BH4 namely 6-hydroxymethyl pterin (HMP) and 6-acetyl 7 7-dimethyl 7 8-dihydropterin (ADDP) were evaluated for vasodilator activity on precontracted rat pulmonary artery rings ADDP was administered to pulmonary hypertensive rats followed by measurement of pulmonary vascular resistance in perfused lungs and eNOS expression by immunohistochemistry ADDP and HMP caused significant relaxation in vitro in rat pulmonary arteries depleted of BH4 with a maximum relaxation at 0 3 mu M (both P<005) Vasodilator activity of ADDP and HMP was completely abolished following preincubation with the NO synthase inhibitor L-NAME ADDP and HMP did not alter relaxation induced by carbachol or spermine NONOate BH4 Itself did not produce relaxation In rats receiving ADDP 141 mg/kg/day pulmonary vasodilation induced by calcium ionophore A23187 was augmented and eNOS immunoreactivity was increased In conclusion ADDP and HMP are two analogues of BH4 which can act as oxidatively stable alternatives to BH4 in causing NO-mediated vasorelaxation Chronic treatment with ADDP resulted in Improvement of NO-mediated pulmonary artery dilation and enhanced expression of eNOS in the pulmonary vascular endothelium Chemically stable analogue, of BH4 may be able to limit endothelial dysfunction in the pulmonary vasculatur
Experimental Realization of a One-way Quantum Computer Algorithm Solving Simon's Problem
We report an experimental demonstration of a one-way implementation of a
quantum algorithm solving Simon's Problem - a black box period-finding problem
which has an exponential gap between the classical and quantum runtime. Using
an all-optical setup and modifying the bases of single-qubit measurements on a
five-qubit cluster state, key representative functions of the logical two-qubit
version's black box can be queried and solved. To the best of our knowledge,
this work represents the first experimental realization of the quantum
algorithm solving Simon's Problem. The experimental results are in excellent
agreement with the theoretical model, demonstrating the successful performance
of the algorithm. With a view to scaling up to larger numbers of qubits, we
analyze the resource requirements for an n-qubit version. This work helps
highlight how one-way quantum computing provides a practical route to
experimentally investigating the quantum-classical gap in the query complexity
model.Comment: 9 pages, 5 figure
Maximal Sharing in the Lambda Calculus with letrec
Increasing sharing in programs is desirable to compactify the code, and to
avoid duplication of reduction work at run-time, thereby speeding up execution.
We show how a maximal degree of sharing can be obtained for programs expressed
as terms in the lambda calculus with letrec. We introduce a notion of `maximal
compactness' for lambda-letrec-terms among all terms with the same infinite
unfolding. Instead of defined purely syntactically, this notion is based on a
graph semantics. lambda-letrec-terms are interpreted as first-order term graphs
so that unfolding equivalence between terms is preserved and reflected through
bisimilarity of the term graph interpretations. Compactness of the term graphs
can then be compared via functional bisimulation.
We describe practical and efficient methods for the following two problems:
transforming a lambda-letrec-term into a maximally compact form; and deciding
whether two lambda-letrec-terms are unfolding-equivalent. The transformation of
a lambda-letrec-term into maximally compact form proceeds in three
steps:
(i) translate L into its term graph ; (ii) compute the maximally
shared form of as its bisimulation collapse ; (iii) read back a
lambda-letrec-term from the term graph with the property . This guarantees that and have the same unfolding, and that
exhibits maximal sharing.
The procedure for deciding whether two given lambda-letrec-terms and
are unfolding-equivalent computes their term graph interpretations and , and checks whether these term graphs are bisimilar.
For illustration, we also provide a readily usable implementation.Comment: 18 pages, plus 19 pages appendi
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Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series
The largest kindred with inherited prion disease P102L, historically Gerstmann-Sträussler-Scheinker syndrome, originates from central England, with émigrés now resident in various parts of the English-speaking world. We have collected data from 84 patients in the large UK kindred and numerous small unrelated pedigrees to investigate phenotypic heterogeneity and modifying factors. This collection represents by far the largest series of P102L patients so far reported. Microsatellite and genealogical analyses of eight separate European kindreds support multiple distinct mutational events at a cytosine-phosphate diester-guanidine dinucleotide mutation hot spot. All of the smaller P102L kindreds were linked to polymorphic human prion protein gene codon 129M and were not connected by genealogy or microsatellite haplotype background to the large kindred or each other. While many present with classical Gerstmann-Sträussler-Scheinker syndrome, a slowly progressive cerebellar ataxia with later onset cognitive impairment, there is remarkable heterogeneity. A subset of patients present with prominent cognitive and psychiatric features and some have met diagnostic criteria for sporadic Creutzfeldt-Jakob disease. We show that polymorphic human prion protein gene codon 129 modifies age at onset: the earliest eight clinical onsets were all MM homozygotes and overall age at onset was 7 years earlier for MM compared with MV heterozygotes (P = 0.02). Unexpectedly, apolipoprotein E4 carriers have a delayed age of onset by 10 years (P = 0.02). We found a preponderance of female patients compared with males (54 females versus 30 males, P = 0.01), which probably relates to ascertainment bias. However, these modifiers had no impact on a semi-quantitative pathological phenotype in 10 autopsied patients. These data allow an appreciation of the range of clinical phenotype, modern imaging and molecular investigation and should inform genetic counselling of at-risk individuals, with the identification of two genetic modifiers
Very high rotational frequencies and band termination in 73Br
Rotational bands in 73Br have been investigated up to spins of 65/2 using the
EUROBALL III spectrometer. One of the negative-parity bands displays the
highest rotational frequency 1.85 MeV reported to date in nuclei with mass
number greater than 25. At high frequencies, the experimental dynamic moment of
inertia for all bands decrease to very low values, indicating a loss of
collectivity. The bands are described in the configuration-dependent cranked
Nilsson-Strutinsky model. The calculations indicate that one of the
negative-parity bands is observed up to its terminating single-particle state
at spin 63/2. This result establishes the first band termination case in the A
= 70 mass region.Comment: 6 pages, 6 figures, submitted to Phys. Rev. C as a Rapid
Communicatio
Physical, chemical and kinetic factors affecting prion infectivity
The mouse-adapted scrapie prion strain RML is one of the most widely used in prion research. The introduction of a cell culture-based assay of RML prions, the scrapie cell assay (SCA) allows more rapid and precise prion titration. A semi-automated version of this assay (ASCA) was applied to explore a range of conditions that might influence the infectivity and properties of RML prions. These include resistance to freeze-thaw procedures; stability to endogenous proteases in brain homogenate despite prolonged exposure to varying temperatures; distribution of infective material between pellet and supernatant after centrifugation, the effect of reducing agents and the influence of detergent additives on the efficiency of infection. Apparent infectivity is increased significantly by interaction with cationic detergents. Importantly, we have also elucidated the relationship between the duration of exposure of cells to RML prions and the transmission of infection. We established that the infection process following contact of cells with RML prions is rapid and followed an exponential time course, implying a single rate-limiting process
The GREAT triggerless total data readout method
Recoil decay tagging (RDT) is a very powerful method for the spectroscopy of exotic nuclei. RDT is a delayed coincidence technique between detectors usually at the target position and at the focal plane of a spectrometer. Such measurements are often limited by dead time. This paper describes a novel triggerless data acquisition method, which is being developed for the Gamma Recoil Electron Alpha Tagging (GREAT) spectrometer, that overcomes this limitation by virtually eliminating dead time. Our solution is a total data readout (TDR) method where all channels run independently and are associated in software to reconstruct events. The TDR method allows all the data from both target position and focal plane to be collected with practically no dead-time losses. Each data word is associated with a timestamp generated from a global 100-MHz clock. Events are then reconstructed in real time in the event builder using temporal and spatial associations defined by the physics of the experimen
Shape coexistence at the proton drip-line: First identification of excited states in 180Pb
Excited states in the extremely neutron-deficient nucleus, 180Pb, have been
identified for the first time using the JUROGAM II array in conjunction with
the RITU recoil separator at the Accelerator Laboratory of the University of
Jyvaskyla. This study lies at the limit of what is presently achievable with
in-beam spectroscopy, with an estimated cross-section of only 10 nb for the
92Mo(90Zr,2n)180Pb reaction. A continuation of the trend observed in 182Pb and
184Pb is seen, where the prolate minimum continues to rise beyond the N=104
mid-shell with respect to the spherical ground state. Beyond mean-field
calculations are in reasonable correspondence with the trends deduced from
experiment.Comment: 5 pages, 4 figures, submitted to Phys.Rev.
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