Photonic Source of Heralded Greenberger-Horne-Zeilinger States.

Generating large multiphoton entangled states is of main interest due to enabling universal photonic quantum computing and all-optical quantum repeater nodes. These applications exploit measurement-based quantum computation using cluster states. Remarkably, it was shown that photonic cluster states of arbitrary size can be generated by using feasible heralded linear optics fusion gates that act on heralded three-photon Greenberger-Horne-Zeilinger (GHZ) states as the initial resource state. Thus, the capability of generating heralded GHZ states is of great importance for scaling up photonic quantum computing. Here, we experimentally demonstrate this required building block by reporting a polarisation-encoded heralded GHZ state of three photons, for which we build a high-rate six-photon source (547±2 Hz) from a solid-state quantum emitter and a stable polarization-based interferometer. The detection of three ancillary photons heralds the generation of three-photon GHZ states among the remaining particles with fidelities up to F=0.7278±0.0106. Our results initiate a path for scalable entangling operations using heralded linear-optics implementations.

Determination of the infectious dose of Helicobacter pylori during primary and secondary infection in rhesus monkeys (Macaca mulatta).

We sought to determine the infectious dose of Helicobacter pylori during primary and secondary infection in the rhesus monkey and to determine whether preinoculation acid suppression is necessary to produce colonization. Mixed inoculation with three human-derived strains showed that H. pylori J166 is particularly adapted to colonization of rhesus monkeys, since it outcompeted two other strains. The minimum infectious dose of H. pylori J166 was 10(4) bacteria in specific-pathogen (H. pylori)-free monkeys. Rechallenge of these monkeys after antibiotic therapy was characterized by a 10- to 100-fold decrease in bacterial load compared to primary infection, but with little change in the infectious dose. Acid suppression prior to inoculation was not necessary for colonization to occur. These results provide a basis for future animal experiments using more ecologically relevant conditions of inoculation and suggest that reduction in bacterial load rather than complete protection may be a more realistic goal for H. pylori vaccination.

Taylorella asinigenitalis sp. nov., a bacterium isolated from the genital tract of male donkeys (Equus asinus).

Three bacterial isolates that were phenotypically indistinguishable from Taylorella equigenitalis were obtained from the urethral fossae of three male donkeys (Equus asinus), one located in the state of California and the other two in the state of Kentucky, USA. Based on results of pulsed-field gel electrophoresis, the isolate from California differed from the two Kentucky isolates, which were the same. Mares bred artificially (California) or naturally (Kentucky) did not show signs of disease, even though infection with the organism was established in those bred naturally. Mares and, uncharacteristically, all three jacks produced antibodies that reacted in the complement fixation test utilized to identify mares recently infected with T. equigenitalis. Sequence analysis of DNA encoding the 16S rRNA revealed that the gene sequences of these isolates were virtually identical to each other (>99.8% similarity), but different (97.6% similarity) from those of several confirmed isolates of T. equigenitalis. The 16S rDNA sequences of the latter were 100% identical. DNA-DNA hybridization studies revealed a mean hybridization level of 89% between the donkey isolate from California and the donkey isolate from Kentucky. On the other hand, the mean DNA-DNA hybridization level from the donkey isolates with DNA from a strain of T. equigenitalis was 23%. The DNA G+C composition was 37.8 mol% for the two donkey isolates, as well as the strain of T. equigenitalis used in the hybridization studies. These data support our opinion that micro-organisms isolated from the male donkeys are different from T. equigenitalis and it is proposed that they be considered a new species within the genus Taylorella and named Taylorella asinigenitalis sp. nov. The type strain is strain UCD-1T (= ATCC 700933T = LMG 19572T).

Selection for urease activity during Helicobacter pylori infection of rhesus macaques (Macaca mulatta).

Helicobacter pylori strain J166 recovered from experimentally inoculated rhesus monkeys had up to a 250-fold-increased urease activity over that before inoculation. This was found to result from the selection of urease positive J166 clones from a heterogeneous inoculum, which was predominantly urease negative due to a 1-bp insertion in the ureA gene. These results confirm the importance of urease for H. pylori colonization. Strain J166 is particularly well adapted to the rhesus monkey, since it colonized preferentially despite the fact that less than 0.1% of the inoculum was urease positive.

Immunization with recombinant Helicobacter pylori urease in specific-pathogen-free rhesus monkeys (Macaca mulatta).

Immunization with urease can protect mice from challenge with Helicobacter pylori, though results vary depending on the particular vaccine, challenge strain, and method of evaluation. Unlike mice, rhesus monkeys are naturally colonized with H. pylori and so may provide a better estimate of vaccine efficacy in humans. The purpose of this study was to examine the effectiveness of H. pylori urease as a vaccine in specific-pathogen (H. pylori)-free rhesus monkeys. Monkeys raised from birth and documented to be free of H. pylori were vaccinated with orogastric (n = 4) or intramuscular (n = 5) urease. Two control monkeys were sham vaccinated. All monkeys were challenged with a rhesus monkey-derived strain of H. pylori, and the effects of vaccination were evaluated by use of quantitative cultures of gastric tissue, histology, and measurement of serum immunoglobulin G (IgG) and salivary IgA. Despite a humoral immune response, all monkeys were infected after H. pylori challenge, and there were no differences in the density of colonization. Immunization with urease therefore does not fully protect against challenge with H. pylori. An effective vaccine to prevent H. pylori infection will require different or more likely additional antigens, as well as improvements in the stimulation of the host immune response.

Selective inhibitors of glial GABA uptake: synthesis, absolute stereochemistry, and pharmacology of the enantiomers of 3-hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole (exo-THPO) and analogues.

3-Methoxy-4,5,6,7-tetrahydro-1,2-benzisoxazol-4-one (20a), or the corresponding 3-ethoxy analogue (20b), and 3-chloro-4,5,6, 7-tetrahydro-1,2-benzisothiazol-4-one (51) were synthesized by regioselective chromic acid oxidation of the respective bicyclic tetrahydrobenzenes 19a,b and 50, and they were used as key intermediates for the syntheses of the target zwitterionic 3-isoxazolols 8-15 and 3-isothiazolols 16 and 17, respectively. These reaction sequences involved different reductive processes. Whereas (RS)-4-amino-3-hydroxy-4,5,6,7-tetrahydro-1,2-benzisoxazole (8, exo-THPO) was synthesized via aluminum amalgam reduction of oxime 22a or 22b, compounds 9, 11-13, and 15-17 were obtained via reductive aminations. Compound 10 was synthesized via N-ethylation of the N-Boc-protected primary amine 25. The enantiomers of 8 were obtained in high enantiomeric purities (ee >/= 99.1%) via the diastereomeric amides 32 and 33, synthesized from the primary amine 23b and (R)-alpha-methoxyphenylacetyl chloride and subsequent separation by preparative HPLC. The enantiomers of 9 were prepared analogously from the secondary amine 27. On the basis of X-ray crystallographic analyses, the configuration of oxime 22a was shown to be E and the absolute configurations of (-)-8 x HCl and (+)-9 x HBr were established to be R. The effects of the target compounds on GABA uptake mechanisms in vitro were measured using a rat brain synaptosomal preparation and primary cultures of mouse cortical neurons and glia cells (astrocytes). Whereas the classical GABA uptake inhibitor, (R)-nipecotic acid (2), nonselectively inhibits neuronal (IC(50) = 12 microM) and glial (IC(50) = 16 microM) GABA uptake and 4,5,6,7-tetrahydroisoxazolo¿4,5-cpyridin-3-ol (1, THPO) shows some selectivity for glial (IC(50) = 268 microM) versus neuronal (IC(50) = 530 microM) GABA uptake, exo-THPO (8) was shown to be more potent as an inhibitor of glial (IC(50) = 200 microM) rather than neuronal (IC(50) = 900 microM) GABA uptake. This selectivity was more pronounced for 9, which showed IC(50) values of 40 and 500 microM as an inhibitor of glial and neuronal GABA uptake, respectively. These effects of 8 and 9 proved to be enantioselective, (R)-(-)-8 and (R)-(+)-9 being the active inhibitors of both uptake systems. The selectivity of 9 as a glial GABA uptake inhibitor was largely lost by replacing the N-methyl group of 9 by an ethyl group, compound 10 being an almost equipotent inhibitor of glial (IC(50) = 280 microM) and neuronal (IC(50) = 400 microM) GABA uptake. The remaining target compounds, 11-17, were very weak or inactive as inhibitors of both uptake systems. Compounds 9-13 and 15 were shown to be essentially inactive against isoniazide-induced convulsions in mice after subcutaneous administration. The isomeric pivaloyloxymethyl derivatives of 9, compounds 43 and 44, were synthesized and tested as potential prodrugs in the isoniazide animal model. Both 43 (ED(50) = 150 micromol/kg) and 44 (ED(50) = 220 micromol/kg) showed anticonvulsant effects, and this effect of 43 was shown to reside in the (R)-(+)-enantiomer, 45 (ED(50) = 44 micromol/kg). Compound 9 also showed anticonvulsant activity when administered intracerebroventricularly (ED(50) = 59 nmol).

Findings of mild traumatic brain injury in combat veterans with PTSD and a history of blast concussion.

Veterans with chronic posttraumatic stress disorder were evaluated for a history of blast concussion, controlling for confounding conditions. Electroencephalograms were analyzed by discriminant function for traumatic brain injury. A difference was found in discriminant scores between veterans with and without blast concussion. More members of the blast group had attentional symptoms and attentional dysfunction. Combat veterans with a remote history of blast injury have persistent electroencephalographic features of traumatic brain injury as well as attentional problems. The authors hypothesize that these constitute a type of chronic postconcussive syndrome that has cognitive and mood symptoms overlapping those of posttraumatic stress disorder.

Aryl and cycloalkyl analogues of AMPA: synthetic, pharmacological and stereochemical aspects.

We have previously shown that (RS)-2-amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid (APPA, 2) is a functional partial agonist at the (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) subtype of excitatory amino acid receptors, reflecting that (S)-APPA is a full agonist and (R)-APPA a competitive antagonist at AMPA receptors. We have now synthesized and pharmacologically characterized (RS)-2-amino-3-[3-hydroxy-5-(2-fluorophenyl)isoxazol-4-yl]propioni c acid (2-F-APPA, 5a), 3-F-APPA (5b), 4-F-APPA (5c), (S)-4-F-APPA (6), (R)-4-F-APPA (7), and the fully and partially, respectively, saturated APPA (2) analogues, (RS)-2-amino-3-(3-hydroxy-5-cyclohexylisoxazol-4-yl)propionic acid (5d) and compound 5e containing a 1-cyclohexenyl ring. The absolute stereochemistry of 6 and 7 was established on the basis of comparative circular dichroism studies on 6, 7, and (S)- and (R)-APPA. 4-F-APPA (5c), (S)-4-F-APPA (6), 5d, and 5e were shown to selectively inhibit [3H]AMPA binding and to activate AMPA receptors. Whereas (S)-4-F-APPA (6) showed full AMPA receptor agonism, (R)-4-F-APPA (7) was an AMPA receptor antagonist. Co-administration of (S)- and (R)-4-F-APPA to the rat cortical wedge preparation produced functional partial AMPA receptor agonism. Semi empirical calculations showed that the magnitude of the torsional angle of the bond connecting the two rings in the series of nonannulated bicyclic AMPA analogues appears to be of importance for the potency and efficacy of these compounds.

The major sigma factor (RpoD) from Helicobacter pylori and other gram-negative bacteria shows an enhanced rate of divergence.

Sequence analysis of the Helicobacter pylori major sigma factor (RpoD) shows that it is highly divergent, which may be related to the marked diversity of the H. pylori chromosome. Furthermore, the rate of divergence of RpoD among other gram-negative bacteria is much greater than that among gram-positive bacteria. This suggests that RpoD from gram-negative bacteria is functionally less constrained than that from gram-positive bacteria.

The effect of cutaneous and deep pain on the electroencephalogram during sleep--an experimental study.

The interaction between sleep and pain has been insufficiently studied, and no experiments have investigated whether pathologic sleep patterns as seen in pain patients can be replicated experimentally by well-defined pain stimuli. An experimental model would therefore be valuable for further studies on the interaction between pain and sleep. In this study, three well-defined experimental stimuli (muscle, joint, and cutaneous pain) were applied during sleep, and the electroencephalogram (EEG) pattern was quantified. The pain stimuli were applied during slow-wave sleep in 10 healthy subjects. Using nine surface recordings, the EEG was sampled before and during pain stimuli. Frequency analysis was performed, resulting in 10 EEG features describing the responses to pain. During the muscle-pain stimulus an arousal effect was observed and a decrease in delta (0.5-3.5 Hz) and sigma (12-14 Hz) as well as increases in alpha 1 (8-10 Hz) and beta (14.5-25 Hz) activities were seen. During joint pain, however, more universal EEG changes were seen with a decrease in the lowest frequency bands [delta, theta (3.5-8 Hz) and alpha 1] and an increase in the higher frequencies [alpha 2 (10-12 Hz), sigma and beta bands]. No background EEG changes were observed during the cutaneous stimulus. There were several differences in the responses from the nine EEG channels, but no derivation seemed especially sensitive to detect the evoked changes. The study highlights the complexity of pain on the sleep EEG. The experimental model has shown that pain from different body structures, as well as signals from various EEG derivations, may give different responses in sleep microstructure.

Concordant anencephaly in monoamniotic twins and an analysis of maternal serum markers.

Anomalies occur with greater frequency in twin gestations than in singleton pregnancies. Anencephaly is not an uncommon defect, but because of its multifactorial inheritance pattern, twins are usually discordant for this anomaly. We present a case of monoamniotic twins concordant for anencephaly. Monoamniotic anencephalic twins were diagnosed at 15 weeks' gestation. Normal interval growth occurred until intrauterine demise of both fetuses at 28 weeks. Maternal serum obtained at 16.5 weeks demonstrated low unconjugated oestriol (uE3) levels and elevated values of alpha-fetoprotein, although this result was lower than expected. Human chorionic gonadotropin (hCG) levels were significantly elevated. Monoamniotic twins concordant for anencephaly occur with extreme rarity. To our knowledge, maternal serum uE3 and hCG levels in fetuses concordant for neural tube defects have not been previously reported.

Obesity and GnRH action. Report of a case with contribution by peripherally derived estrogens.

BACKGROUND: Gonadotropin-releasing hormone agonists (GnRH-a) are effective in reducing the pituitary release of gonadotropins, which, in turn, decrease ovarian steroidogenesis. The resulting menopausal state decreases the volume and vascular supply to uterine leiomyomas. Peripheral adipose tissue also contributes significantly to the circulatory estrogen pool, which is formed independent of pituitary function. As such, obesity may interfere with depot leuprolide acetate effects, allowing normal estrogen levels despite gonadotropin suppression. CASE: A premenopausal, morbidly obese woman was referred for treatment of menorrhagia and uterine leiomyomas. Despite administration of depot leuprolide, a GnRH-a, she continued to bleed heavily. Serum estradiol levels remained in the normal range, with suppression of follicle-stimulating hormone (FSH) levels. The desired hypoestrogenic effect from GnRH-a administration was thought to be negated by estradiol levels arising from peripherally derived conversion of adrenal androgens in adipose tissue. A GnRH stimulation test was performed to evaluate the responsiveness of the pituitary to the above therapy. While FSH was suppressed and unresponsive to stimulation, estradiol remained unchanged. CONCLUSION: Peripheral production of estrogen appears to be unaffected by leuprolide administration. Consideration should be given to the patient's body habitus when administering a GnRH suppressant. Morbidly obese patients possess an unlimited reservoir for peripheral estrogen synthesis.

Pasteurella multocida enters polarized epithelial cells by interacting with host F-actin.

We investigated the interaction of an avian strain of Pasteurella multocida with the cytoskeleton of MDCK cells, which formed a polarized epithelium when grown on type I collagen coated filters. Bacteria were incubated with MDCK cells for 30 min. 2, 4 and 6 hours and their location and association with the cell cytoskeleton determined by double-label immunofluorescence confocal microscopy. Cells were stained with a polyclonal antiserum to the outer-membrane proteins of P. multocida and with rhodamine phalloidin which specifically binds filamentous (F) actin. Confocal microscopy revealed that bacteria entered the cells by 30 min, and that by 6 hours there was a marked alteration in the actin cytoskeleton in which long filaments were reorganized to discrete foci of short actin filaments, within which were one or more bacteria. Electron microscopy demonstrated that by 2 hours, each bacterium was associated with many short 5-6 nm filaments. Treatment of MDCK cells with cytochalasin D for either 30 minutes or 24 hours prior to infection disrupted the actin cytoskeleton and inhibited entry of P. multocida.

Haloperidol overdose during pregnancy.

BACKGROUND: Suicide attempts during pregnancy are rare. Over-the-counter and psychotropic medications are most commonly used. Although intentional overdose of haloperidol has been reported in nonpregnant adults, it has not, to our knowledge, been reported previously during pregnancy. In this case of suicide attempt by haloperidol overdose, maternal and fetal responses were studied extensively. CASE: Intentional ingestion of 300 mg haloperidol by a pregnant woman at 34 weeks' gestation caused maternal unresponsiveness, an extrapyramidal reaction, temporary fetal akinesia, and a nonreactive nonstress test. The mother recovered in 48 hours. The fetus did not reach a biophysical profile score of ten until 5 days after presentation. CONCLUSION: Haloperidol overdose during pregnancy causes a maternal extrapyramidal reaction, temporary fetal akinesia, and prolonged fetal neuromuscular depression.

Distribution of tet(H) among Pasteurella isolates from the United States and Canada.

Tetracycline-resistant isolates of Pasteurella multocida and Pasteurella haemolytica obtained from various locations in the United States and Canada were studied to determine the distribution of the tet(H) gene. Of the 31 isolates examined, 25 were found to contain the tet(H) gene. Chromosomal or plasmid DNA obtained from those that did not contain the tet(H) gene did not hybridize with probes specific for classes A through G, though chromosomal DNA from one isolate lacking tet(H) hybridized with a probe specific for class M. The tet(H) gene was found on plasmid as well as on chromosomal DNA, suggesting that it is carried on a transposable element.

Evaluating ovarian reserve: follicle stimulating hormone and oestradiol variability during cycle days 2-5.

A prospective measurement of follicle stimulating hormone (FSH) and oestradiol between cycle days 2 and 5 was conducted to investigate the intra- and inter-cycle variability in a healthy population of women with regular menstrual intervals. Daily serum samples were obtained from 44 women for a total of 66 cycles on cycle days 2, 3, 4 and 5. FSH concentrations were consistent on all cycle days measured. Oestradiol concentrations on cycle day 2 were not different from cycle day 3, but concentrations on cycle day 4 and cycle day 5 were statistically different from both cycle day 2 and cycle day 3 by analysis of variance (P < or = 0.05). Evaluation of functional ovarian reserved by cycle day 3 FSH measurement has become the standard in most assisted reproductive technology programmes. The recent change in FSH standardization coupled with the inflexibility of cycle day 3 testing has led to a re-evaluation of testing protocols. Cycle day 3 appears to have emerged as a dictum because most ovulation induction protocols are initiated on cycle day 3, 4 or 5. Flexibility of sampling day can be introduced as suggested by these results. The additional information ascertained from oestradiol testing as applied to evaluation of ovarian reserve warrants further investigation.

Cloning and sequence of the groESL heat-shock operon of Pasteurella multocida.

By using degenerate oligodeoxyribonucleotide primers for conserved regions of groEL, a 0.6-kb fragment of Pasteurella multocida genomic DNA was amplified using PCR. The amplified fragment was then used as a probe to isolate a genomic fragment containing the entire GroESL operon. The isolated genomic fragment was found to contain two open reading frames, the sequences of which were highly homologous to the prokaryotic groES and groEL families of genes.