Extended Crossover from a Fermi Liquid to a Quasiantiferromagnet in the Half-Filled 2D Hubbard Model.

The ground state of the Hubbard model with nearest-neighbor hopping on the square lattice at half filling is known to be that of an antiferromagnetic (AFM) band insulator for any on-site repulsion. At finite temperature, the absence of long-range order makes the question of how the interaction-driven insulator is realized nontrivial. We address this problem with controlled accuracy in the thermodynamic limit using self-energy diagrammatic determinant Monte Carlo and dynamical cluster approximation methods and show that development of long-range AFM correlations drives an extended crossover from Fermi liquid to insulating behavior in the parameter regime that precludes a metal-to-insulator transition. The intermediate crossover state is best described as a non-Fermi liquid with a partially gapped Fermi surface.

Simulation of the NMR response in the pseudogap regime of the cuprates.

The pseudogap in the cuprate high-temperature superconductors was discovered as a suppression of the Knight shift and spin relaxation time measured in nuclear magnetic resonance (NMR) experiments. However, theoretical understanding of this suppression in terms of the magnetic susceptiblility of correlated itinerant fermion systems was so far lacking. Here we study the temperature and doping evolution of these quantities on the two-dimensional Hubbard model using cluster dynamical mean field theory. We recover the suppression of the Knight shift and the linear-in-T spin echo decay that increases with doping. The relaxation rate shows a marked increase as T is lowered but no indication of a pseudogap on the Cu site, and a clear downturn on the O site, consistent with experimental results on single layer materials but different from double layer materials. The consistency of these results with experiment suggests that the pseudogap is well described by strong short-range correlation effects.

Superconducting fluctuations in the normal state of the two-dimensional Hubbard model.

We compute the two-particle quantities relevant for superconducting correlations in the two-dimensional Hubbard model within the dynamical cluster approximation. In the normal state we identify the parameter regime in density, interaction, and second-nearest-neighbor hopping strength that maximizes the d_{x^{2}-y^{2}} superconducting transition temperature. We find in all cases that the optimal transition temperature occurs at intermediate coupling strength, and is suppressed at strong and weak interaction strengths. Similarly, superconducting fluctuations are strongest at intermediate doping and suppressed towards large doping and half filling. We find a change in sign of the vertex contributions to d_{xy} superconductivity from repulsive near half filling to attractive at large doping. p-wave superconductivity is not found at the parameters we study, and s-wave contributions are always repulsive. For negative second-nearest-neighbor hopping the optimal transition temperature shifts towards the electron-doped side in opposition to the van Hove singularity, which moves towards hole doping. We surmise that an increase of the local interaction of the electron-doped compounds would increase T_{c}.

Fluctuation Diagnostics of the Electron Self-Energy: Origin of the Pseudogap Physics.

We demonstrate how to identify which physical processes dominate the low-energy spectral functions of correlated electron systems. We obtain an unambiguous classification through an analysis of the equation of motion for the electron self-energy in its charge, spin, and particle-particle representations. Our procedure is then employed to clarify the controversial physics responsible for the appearance of the pseudogap in correlated systems. We illustrate our method by examining the attractive and repulsive Hubbard model in two dimensions. In the latter, spin fluctuations are identified as the origin of the pseudogap, and we also explain why d-wave pairing fluctuations play a marginal role in suppressing the low-energy spectral weight, independent of their actual strength.

Optical self-energy in graphene due to correlations.

In highly correlated systems one can define an optical self-energy in analogy to its quasiparticle (QP) self-energy counterpart. This quantity provides useful information on the nature of the excitations involved in inelastic scattering processes. Here we calculate the self-energy of the intraband optical transitions in graphene originating in the electron-electron interaction (EEI) as well as electron-phonon interaction (EPI). Although optics involves an average over all momenta (k) of the charge carriers, the structure in the optical self-energy is nevertheless found to mirror mainly that of the corresponding quasiparticles for k equal to or near the Fermi momentum k(F). Consequently, plasmaronic structures which are associated with momenta near the Dirac point at k = 0 are not important in the intraband optical response. While the structure of the electron-phonon interaction (EPI) reflects the sharp peaks of the phonon density of states, the excitation spectrum associated with the electron-electron interaction is in comparison structureless and flat and extends over an energy range which scales linearly with the value of the chemical potential. We introduce a method whereby detailed quantitative information on such excitation spectra can be extracted from optical data. Modulations seen on the edge of the interband optical conductivity as it rises towards its universal background value are traced to structure in the quasiparticle self-energies around k(F) of the lower Dirac cone associated with the occupied states.

Analysis of time management in stroke patients in three French emergency departments: from stroke onset to computed tomography scan.

The aim of this study was to determine and identify the factors associated with shortening or lengthening time interval from stroke onset to performance of computed tomography (CT) scan in stroke patients admitted to three French emergency departments. All suspected stroke patients were eligible (n = 317). The time intervals between stroke onset and presentation to the emergency department and between CT scan request and CT scan performance were determined. Twelve variables likely to influence time interval before presentation to the emergency department, and five variables likely to influence time interval before CT scan performance were evaluated using stepwise regression analysis. Of the 317 patients included in the study, the mean time interval from stroke onset to CT scan performance for 180 patients was 7 hours 46 minutes (466 minutes). The mean time interval between stroke onset and presentation to the emergency department was 4 hours 36 minutes (276 minutes), varying according to the study site, level of initial severity, medical contact before admission, witnesses at stroke onset, and mode of transportation. The mean time interval between request and CT scan performance was 2 hours 14 minutes (134 minutes), varying upon the site, hour of CT scan request, type of stroke and level of severity at admission. It is concluded that current delays in stroke management are often incompatible with early treatment. The public needs to be informed and admission procedures reorganized. Improved response to the urgency of ischaemic stroke is required as well as direct access to the scanner during periods of scheduled use.

Genetic determinants of Pseudomonas aeruginosa colonization in cystic fibrosis patients in Canada.

The present study was aimed at analyzing whether the rate of colonization and the age at colonization with Pseudomonas aeruginosa was genetically determined in cystic fibrosis (CF) patients. These two variables were calculated among 127 CF patients whose genotypes were known and who were monitored at the Clinique de Fibrose Kystique in Saguenay Lac-Saint-Jean. No statistically significant differences were found in the rate or the age at colonization when the patients were grouped by genotype; however, this result could be due to the small number of patients in each genotype group. The rate of colonization was significantly lower among CF patients carrying the A455E mutation, a "mild" allele with respect to exocrine pancreatic function, than among those carrying either the deltaF508 or the 621 + IG- > T mutation, both of which are "severe" alleles. The results confirm previous reports that the rate of colonization with Pseudomonas aeruginosa is, at least in part, genetically determined.

Phenotypic variability in five cystic fibrosis patients compound heterozygous for the Y1092X mutation.

Five cystic fibrosis (CF) patients distributed in three families and compound heterozygotes for the Y1092X mutation have been followed for a period ranging from 5 to 20 years. The genealogical reconstruction identified a common ancestor couple to all 3 families at the 5th generation. All 5 patients were pancreatic insufficient. A high variability in the clinical aspects and pulmonary function was seen between the families, but not within. Based on our observations, it will be very difficult to predict the course of disease for CF patients with the Y1092X mutation, even if they are closely related (first-degree cousins).

Correlation of sweat chloride concentration with genotypes in cystic fibrosis patients in Saguenay Lac-Saint-Jean, Quebec, Canada.

OBJECTIVES: Saguenay Lac-Saint-Jean, a geographically isolated region of northeastern Quebec has a high incidence of cystic fibrosis (CF) and three mutations only account for 94% of the CF chromosomes. The objective of the present study was to determine whether different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene had different effects upon the sweat chloride concentration. DESIGN AND METHODS: The sweat chloride concentration of 114 patients was measured by quantitative pilocarpine iontophoresis. RESULTS: CF patients carrying the A455E mutation, usually associated with pancreatic sufficiency, had lower sweat chloride concentrations than those carrying mutations associated with pancreatic insufficiency (delta F508 and 621 + 1G-->T). CONCLUSIONS: Our results confirm that mutations resulting in a reduction of the chloride current at the apical membrane of epithelial cells induce lower sweat chloride values. However, there are differences in the chloride current between genotypes, even if they are composed of mutations apparently having the same functional effect.

Complete identification of cystic fibrosis transmembrane conductance regulator mutations in the CF population of Saguenay Lac-Saint-Jean (Quebec, Canada).

Over the past few years, we have conducted a systematic study of 230 cystic fibrosis (CF) chromosomes in the Saguenay Lac-Saint-Jean (SLSJ) population which has a high CF incidence (1/936 live births). We identified 11 mutations accounting for 100% of the CF chromosomes found in patients born in SLSJ. Our results indicate that denaturing gradient gel electrophoresis (DGGE) is a powerful method of identifying CF mutations. They have also considerable implications for genetic counselling and molecular characterization of doubtful patients. They make carrier screening technically feasible in this population.

Genotype-phenotype correlation in cystic fibrosis patients compound heterozygous for the A455E mutation.

Cystic fibrosis (CF) has a high incidence in the French-Canadian population of Saguenay Lac-Saint-Jean (Quebec). The A455E mutation accounts for 8.3% of the CF chromosomes. This mutation was shown to be associated with a milder lung disease in the Dutch population. Twenty two CF patients distributed in 17 families and compound heterozygotes for the A455E mutation have been followed at the Clinique de Fibrose Kystique de Chicoutimi. Fourteen patients also carried the delta F508 mutation while the remaining eight patients had the 621 + 1G-->T mutation. Each patient was matched by sex and age to a patient homozygous for the delta F508 mutation. The pairs were analyzed for several clinical and laboratory variables. The A455E compound heterozygotes were diagnosed at a later age (P = 0.003) and had chloride concentrations at the sweat test lower than those homozygous for the delta F508 mutation (P = 0.007). More patients were pancreatic sufficient (P = 0.004). They had a higher Shwachman score (P = 0.001) and better pulmonary function tests (P < 0.02). CF patients compound heterozygous for the A455E mutation have a milder pancreatic and lung disease than the delta F508 homozygotes. Therefore, the A455E should be associated with a better prognosis.

Clinical features of cystic fibrosis patients with rare genotypes in Saguenay Lac-Saint-Jean (Quebec, Canada).

We describe the clinical features of six cystic fibrosis (CF) patients from Saguenay Lac-Saint-Jean who bear rare genotypes. Two patients with a delta F508/I148T genotype had pancreatic insufficiency, as did two patients compound heterozygous for the 621 + 1G-->T mutation who also had a major growth retardation. One CF adult who carried a delta F508/Q890X genotype had meconium ileus and bronchiectasis. The sixth patient (A455E/R117C) had borderline sweat chloride concentrations; the diagnosis of cystic fibrosis had remained doubtful until the molecular analysis showed the presence of two CF mutations. The seventh patient with a delta F508/R1158X genotype experienced several complications and is now 43 years old.

Quality criteria for chromatographic analytical systems of polyunsaturated fatty acids metabolites.

The most powerful technique for eicosanoids identification is gas chromatography prior to mass spectrometry. Results are highly dependent upon the choice of appropriate gas chromatographic systems; the critical point of the system being the quality of the column. Our work is intended to provide a general overview of open tubular capillary columns which can be used for separation, identification and quantification of eicosanoids.

Excision of uracil residues in DNA: mechanism of action of Escherichia coli and Micrococcus luteus uracil-DNA glycosylases.

Various octadeoxynucleotides containing uracil at different positions were synthesized and submitted to the action of Escherichia coli and Micrococcus luteus uracil-DNA glycosylases. A uracil residue situated at the 5'-end was excised by the M.luteus enzyme but not by the E.coli one. Uracil residues located at the ultimate and penultimate positions at the 3'-end were not cleaved by either enzymes. At the other central positions, uracil was eliminated with different initial velocities. Single stranded phi X 174 DNA fragments were used to study the influence of the sequence. Cytosine bases were deaminated to give uracil by bisulfite treatment. It was shown that the initial excision velocity of two vicinal uracil residues was decreased. The same observation was made for two uracils separated by one base. A hypothetical scheme is suggested to explain the mechanism of action of uracil-DNA glycosylases.

Comparison at the molecular level of uracil-DNA glycosylases from different origins.

A nuclear and a cytoplasmic uracil-DNA glycosylase have been purified from epithelial cells derived from a rat hepatoma (H4 cells) cultured in vitro. They have different optimum pH, molecular weight, isoelectric points, activation energy, Km. Uracil acts as a non competitive inhibitor towards the nuclear enzyme while it is a competitive one for the cytoplasmic enzyme. Comparison of the properties of the two mammalian enzymes with those of the enzymes isolated from Escherichia coli and Micrococcus luteus shows that they all behave differently. The following criteria were studied: molecular weight, optimum pH, isoelectric point, inhibition by uracil analogs, modulation of their activity by polyamines or by intercalating drugs. The only common properties shared by these four enzymes are: an activity twice as high on single stranded DNA than on double stranded DNA and no requirement for divalent cation for maximal activity.

Uracil-DNA glycosylase. Purification and properties of uracil-DNA glycosylase from Micrococcus luteus.

A uracil-DNA-glycosylase from Micrococcus luteus has been purified more than 3,000-fold. The enzyme preparation appears homogeneous, according to the results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It is devoid of nonspecific endonucleases, specific endonucleases for apurinic and apyrimidinic sites, 3-methyladenine or 7-methylguanine-DNA-glycosylases. It behaves as a monomer protein of 19,400 daltons. It has an isoelectric point of 7.0 +/- 0.1. It has an optimal activity between pH 5.0 and 7.0. It has no cofactor requirement and is not inhibited by EDTA. Uracil-DNA-glycosylase is highly specific for DNA containing dUMP residues, releasing uracil as product of the reaction. It is 2-fold more active on single-stranded DNA than on double-stranded DNA. If it releases uracil dimers from ultraviolet-irradiated PBS1 DNA, it is at the threshold of the detection. The apparent Km is 7 X 10(-8) M, and uracil acts as a noncompetitive inhibitor with a Ki of 3.2 X 10(-4) M. Cis-syn cyclogbutadiuracil also is a potent inhibitor, while some analogs, produced by x-irradiation of uracil and thymine, are weak inhibitors. Spermine, between 10 and 400 microM, increases the enzymatic activity by 50% and is not inhibitory at other concentrations. Spermidine activates the enzyme at concentrations of 40 to 120 microM, but becomes inhibitory at 200 and 400 microM. A new finding is that drugs which intercalate in DNA, such as ethidium bromide and ellipticine, cause a 2- to 2.5-fold activation of this enzyme activity. The concentrations giving maximal activation depend on the drug. The enzyme does not behave as a processive enzyme during uracil excision.