The impact of oral herpes simplex virus infection and candidiasis on chemotherapy-induced oral mucositis among patients with hematological malignancies.

The aim of this study was to evaluate the influences of oral candidiasis and herpes simplex virus 1 (HSV-1) infections in chemotherapy-induced oral mucositis (OM). The medical records of 424 consecutive patients with hematological malignancies who had received chemotherapy at a medical center in Taiwan from January 2006 to November 2007 were retrospectively reviewed. The results of swab cultures of fungus and HSV-1 for OM were correlated with associated clinical features. Younger age, myeloid malignancies, and disease status other than complete remission before chemotherapy were significantly correlated with the development of OM. Risks of fever (p < 0.001) and bacteremia were higher in patients with OM. Among 467 episodes of OM with both swab cultures available, 221 were non-infection (47.3%) and 246 were related to either fungal infections, HSV-1 infections, or both (52.7%); of the 246 episodes, 102 were associated with fungal infections alone (21.8%), 98 with HSV-1 infections alone (21%), and 46 with both infections (9.9%). Patients who had received antifungal agents prior to OM occurrence tended to have HSV-1 infection (p < 0.001). Our results suggest that Candida albicans and HSV-1 play an important role in chemotherapy-induced OM in patients with hematological malignancies.

Preparation and measurement of three-qubit entanglement in a superconducting circuit.

Traditionally, quantum entanglement has been central to foundational discussions of quantum mechanics. The measurement of correlations between entangled particles can have results at odds with classical behaviour. These discrepancies grow exponentially with the number of entangled particles. With the ample experimental confirmation of quantum mechanical predictions, entanglement has evolved from a philosophical conundrum into a key resource for technologies such as quantum communication and computation. Although entanglement in superconducting circuits has been limited so far to two qubits, the extension of entanglement to three, eight and ten qubits has been achieved among spins, ions and photons, respectively. A key question for solid-state quantum information processing is whether an engineered system could display the multi-qubit entanglement necessary for quantum error correction, which starts with tripartite entanglement. Here, using a circuit quantum electrodynamics architecture, we demonstrate deterministic production of three-qubit Greenberger-Horne-Zeilinger (GHZ) states with fidelity of 88 per cent, measured with quantum state tomography. Several entanglement witnesses detect genuine three-qubit entanglement by violating biseparable bounds by 830 ± 80 per cent. We demonstrate the first step of basic quantum error correction, namely the encoding of a logical qubit into a manifold of GHZ-like states using a repetition code. The integration of this encoding with decoding and error-correcting steps in a feedback loop will be the next step for quantum computing with integrated circuits.

Demonstration of two-qubit algorithms with a superconducting quantum processor.

Quantum computers, which harness the superposition and entanglement of physical states, could outperform their classical counterparts in solving problems with technological impact-such as factoring large numbers and searching databases. A quantum processor executes algorithms by applying a programmable sequence of gates to an initialized register of qubits, which coherently evolves into a final state containing the result of the computation. Building a quantum processor is challenging because of the need to meet simultaneously requirements that are in conflict: state preparation, long coherence times, universal gate operations and qubit readout. Processors based on a few qubits have been demonstrated using nuclear magnetic resonance, cold ion trap and optical systems, but a solid-state realization has remained an outstanding challenge. Here we demonstrate a two-qubit superconducting processor and the implementation of the Grover search and Deutsch-Jozsa quantum algorithms. We use a two-qubit interaction, tunable in strength by two orders of magnitude on nanosecond timescales, which is mediated by a cavity bus in a circuit quantum electrodynamics architecture. This interaction allows the generation of highly entangled states with concurrence up to 94 per cent. Although this processor constitutes an important step in quantum computing with integrated circuits, continuing efforts to increase qubit coherence times, gate performance and register size will be required to fulfil the promise of a scalable technology.

Randomized benchmarking and process tomography for gate errors in a solid-state qubit.

We present measurements of single-qubit gate errors for a superconducting qubit. Results from quantum process tomography and randomized benchmarking are compared with gate errors obtained from a double pi pulse experiment. Randomized benchmarking reveals a minimum average gate error of 1.1+/-0.3% and a simple exponential dependence of fidelity on the number of gates. It shows that the limits on gate fidelity are primarily imposed by qubit decoherence, in agreement with theory.

Controlling the spontaneous emission of a superconducting transmon qubit.

We present a detailed characterization of coherence in seven transmon qubits in a circuit QED architecture. We find that spontaneous emission rates are strongly influenced by far off-resonant modes of the cavity and can be understood within a semiclassical circuit model. A careful analysis of the spontaneous qubit decay into a microwave transmission-line cavity can accurately predict the qubit lifetimes over 2 orders of magnitude in time and more than an octave in frequency. Coherence times T1 and T_{2};{*} of more than a microsecond are reproducibly demonstrated.

Generating single microwave photons in a circuit.

Microwaves have widespread use in classical communication technologies, from long-distance broadcasts to short-distance signals within a computer chip. Like all forms of light, microwaves, even those guided by the wires of an integrated circuit, consist of discrete photons. To enable quantum communication between distant parts of a quantum computer, the signals must also be quantum, consisting of single photons, for example. However, conventional sources can generate only classical light, not single photons. One way to realize a single-photon source is to collect the fluorescence of a single atom. Early experiments measured the quantum nature of continuous radiation, and further advances allowed triggered sources of photons on demand. To allow efficient photon collection, emitters are typically placed inside optical or microwave cavities, but these sources are difficult to employ for quantum communication on wires within an integrated circuit. Here we demonstrate an on-chip, on-demand single-photon source, where the microwave photons are injected into a wire with high efficiency and spectral purity. This is accomplished in a circuit quantum electrodynamics architecture, with a microwave transmission line cavity that enhances the spontaneous emission of a single superconducting qubit. When the qubit spontaneously emits, the generated photon acts as a flying qubit, transmitting the quantum information across a chip. We perform tomography of both the qubit and the emitted photons, clearly showing that both the quantum phase and amplitude are transferred during the emission. Both the average power and voltage of the photon source are characterized to verify performance of the system. This single-photon source is an important addition to a rapidly growing toolbox for quantum optics on a chip.

Coupling superconducting qubits via a cavity bus.

Superconducting circuits are promising candidates for constructing quantum bits (qubits) in a quantum computer; single-qubit operations are now routine, and several examples of two-qubit interactions and gates have been demonstrated. These experiments show that two nearby qubits can be readily coupled with local interactions. Performing gate operations between an arbitrary pair of distant qubits is highly desirable for any quantum computer architecture, but has not yet been demonstrated. An efficient way to achieve this goal is to couple the qubits to a 'quantum bus', which distributes quantum information among the qubits. Here we show the implementation of such a quantum bus, using microwave photons confined in a transmission line cavity, to couple two superconducting qubits on opposite sides of a chip. The interaction is mediated by the exchange of virtual rather than real photons, avoiding cavity-induced loss. Using fast control of the qubits to switch the coupling effectively on and off, we demonstrate coherent transfer of quantum states between the qubits. The cavity is also used to perform multiplexed control and measurement of the qubit states. This approach can be expanded to more than two qubits, and is an attractive architecture for quantum information processing on a chip.

Gate-defined quantum dots on carbon nanotubes.

We report the realization of nanotube-based multiple quantum dots that are fully defined and controlled with electrostatic gates. Metallic top-gates are used to produce localized depletion regions in the underlying tubes; a pair of such depletion regions in a nanotube with ohmic contact electrodes defines the quantum dot. Top-gate voltages tune the transparencies of tunnel barriers as well as the electrostatic energies within single and multiple dots. This approach allows precise control over multiple devices on a single tube, and serves as a design paradigm for nanotube-based electronics and quantum systems.

Survival of Aspergillus fumigatus in serum involves removal of iron from transferrin: the role of siderophores.

Aspergillus fumigatus is a filamentous fungus which can cause invasive disease in immunocompromised individuals. A. fumigatus can grow in medium containing up to 80% human serum, despite very low concentrations of free iron. The purpose of this study was to determine the mechanism by which A. fumigatus obtains iron from the serum iron-binding protein transferrin. In iron-depleted minimal essential medium (MEM), A. fumigatus growth was supported by the addition of holotransferrin (holoTf) or FeCl(3) but not by the addition of apotransferrin (apoTf). Proteolytic degradation of transferrin by A. fumigatus occurred in MEM-serum; however, transferrin degradation did not occur until late logarithmic phase. Moreover, transferrin was not degraded by A. fumigatus incubated in MEM-holoTf. Urea polyacrylamide gel electrophoresis showed that in MEM-holoTf, holoTf was completely converted to apoTf by A. fumigatus. In human serum, all of the monoferric transferrin was converted to apoTf within 8 h. Siderophores were secreted by A. fumigatus after 8 h of growth in MEM-serum and 12 h in MEM-holoTf. The involvement of small molecules in iron acquisition was confirmed by the fact that transferrin was deferrated by A. fumigatus even when physically separated by a 12-kDa-cutoff membrane. Five siderophores were purified from A. fumigatus culture medium, and the two major siderophores were identified as triacetylfusarinine C and ferricrocin. Both triacetylfusarinine C and ferricrocin removed iron from holoTf with an affinity comparable to that of ferrichrome. These data indicate that A. fumigatus survival in human serum in vitro involves siderophore-mediated removal of iron from transferrin. Proteolytic degradation of transferrin may play a secondary role in iron acquisition.

Rapid reversal of hyperoxaluria in a rat model after probiotic administration of Oxalobacter formigenes.

PURPOSE: The gut inhabiting bacterium Oxalobacter formigenes may be a negative risk factor in recurrent calcium oxalate kidney stone disease that apparently maintains oxalic acid homeostasis in its host via the degradation of dietary oxalate. The possibility of using this bacterium as probiotic treatment to reduce urinary oxalate was investigated in a rat model. MATERIALS AND METHODS: Male Sprague-Dawley rats were placed on a diet supplemented with ammonium oxalate to induce a state of severe hyperoxaluria. Subgroups of these rats received an esophageal gavage of 1 x 10(3), 10(5), 10(7) or 10(9) O. formigenes per feeding for a 2-week period. Each rat was followed for general health and changes in urinary oxalate. RESULTS: Rats with chronic hyperoxaluria resulting from high dietary oxalate that were treated with O. formigenes showed decreased urinary oxalate within 2 days of initiating probiotic supplementation. The amount of the decrease in a 2-week period proved directly proportional to the dose of bacteria. Urinary oxalate in rats receiving higher amounts of O. formigenes returned to almost normal. Throughout the study the rats remained healthy with no signs of toxicity, antibody development or a histopathological condition. CONCLUSIONS: Probiotic treatment of hyperoxaluric rats with O. formigenes may significantly and rapidly reduce the level of oxalate in the urine. This probiotic treatment appears to be safe and well tolerated. The approach may be feasible for treating calcium oxalate kidney stone disease.

Hydrothermal syntheses, structures, and properties of [Cu3Cl2CN(pyrazine)] and copper(I) halide pyrazine polymers.

Crystals of copper halide and pseudohalide compounds with pyrazine are synthesized under hydrothermal conditions. The title compound, [Cu3Cl2CNPz] (1) (Pz = pyrazine), is a new copper compound exhibiting an unusual -(Cu3Cl2)- polymeric stair structural motif and three-coordinate cyanide. Compound 1 crystallizes in the monoclinic space group P2(1)/m, with a = 3.6530(7) A, b = 17.160(3) A, c = 6.9800(14) A, beta = 90.58(3) degrees, and Z = 2. In addition, the series of complexes [Cu2X2Pz] for X = Cl (2), Br (3), and I (4) are also crystallized under hydrothermal conditions. The inorganic polymer [Cu2Br2Pz] (3) belongs to the triclinic space group P1, with a = 6.9671(14) A, b = 7.849(2) A, c = 8.099(2) A, alpha = 71.69(3) degrees, beta = 70.71(3) degrees, gamma = 85.43(3) degrees, and Z = 2. The structure of 3, is similar to the recently reported structure for [Cu2Cl2Pz] (2) (Kawata, S.; Kitagawa, S.; Kumagai, H.; Iwabuchi, S.; Katada, M. Inorg. Chim. Acta 1998, 267, 143). The third member of the series, [Cu2I2Pz], is found to be isostructural on the basis of X-ray powder diffraction results. The lattice parameters are refined from indexed reflections to a = 7.115(10) A, b = 8.321(19) A, c = 8.378(17) A, alpha = 71.1(3) degrees, beta = 67.3(1) degrees, and gamma = 83.0(2) degrees. Electronic spectra show that compounds 1-4 have optical band gaps in the range 2.2-2.4 eV. The infrared and Raman spectra as well as the thermal properties of all compounds are presented.

Effect of protease-activated receptor (PAR)-1, -2 and -4-activating peptides, thrombin and trypsin in rat isolated airways.

Mechanisms of relaxation and contraction to protease-activated receptor- (PAR) tethered ligand peptides (SFLLRN/TFLLR, SLIGRL and GYPGKF (all C-terminally amidated) for PAR1, PAR2 and PAR4, respectively) and enzymes (thrombin and trypsin) were investigated in isolated segments of rat trachea, main and first order intrapulmonary bronchi. In airway segments previously exposed to SLIGRL, SFLLRN caused contractions that were potentiated by indomethacin, but were independent of mast cell degranulation. Contractions to TFLLR in the intrapulmonary bronchi were similarly potentiated by indomethacin. SLIGRL caused epithelium-dependent relaxations which were unaffected by N(G)-nitro-L-arginine, 1-H-oxodiazol-[1,2,4]-[4,3-a]quinoxaline-1-one or zinc-protoporphyrin-IX but were abolished by haemoglobin in all three regions of the airways. Relaxations to SLIGRL were markedly attenuated by indomethacin only in the main and intrapulmonary bronchi. GYPGKF caused epithelium-dependent relaxations in all three regions of the airway which were only significantly inhibited by indomethacin in the intrapulmonary bronchi. In general, thrombin and trypsin failed to cause any response in the airways tested. Intense PAR2-immunoreactivity was observed on airway epithelium. PAR1-immunoreactivity was faint on airway epithelium and smooth muscle, but was prevalent in mast cells. These findings indicate that PAR2 and possibly PAR4 present on rat airway epithelia mediate smooth muscle relaxation via cyclo-oxygenase-dependent and -independent mechanisms. PAR1-mediated contractions were most likely due to activation of smooth muscle receptors. The general failure of thrombin and trypsin to cause responses which may have been due to endogenous protease inhibitors, highlights the need for caution in assessing pathophysiological roles for PARs if only enzymes are used to activate PARs.

Protease-activated receptor-2 turnover stimulated independently of receptor activation in porcine coronary endothelial cells.

1. Protease-activated receptors (PARs) are activated by an irreversible proteolytic mechanism which renders cleaved receptors unresponsive to subsequent challenges with activating enzymes. Non-specific proteolysis of PARs downstream of the activation site also prevents subsequent enzymic activation. Therefore, we investigated the effects of non-activating amino-terminal proteolysis with the bacterial protease thermolysin on PAR-mediated relaxation of porcine coronary artery ring preparations contracted with the thromboxane A2 mimetic U46619 (1-10 nM). 2. Treatment of contracted artery ring segments with thermolysin (0.01-1 u ml-1, 20 min) caused no response, but abolished endothelium-dependent relaxations induced by the enzymic activators of PAR-1, and PAR-2, thrombin (0.01-0.3 u ml-1) and trypsin (0.003-0.1 u ml-1) respectively. The same treatment, however, did not affect similar responses to the proteolysis-independent PAR-1 and PAR-2 activating peptides, SFLLRN-NH2 and SLIGRL-NH2 respectively (0.1-10 microM). 3. The inhibition of responsiveness to trypsin after thermolysin treatment recovered in a time-dependent manner, with maximal recovery (77.3 +/- 8.0% of time controls) occurring 150 min after thermolysin treatment. No recovery of responsiveness to thrombin after thermolysin treatment was observed within this time, however, the thrombin response returned to control levels after 20 h. 4. The recovery of responsiveness to trypsin was inhibited by the translation inhibitor cycloheximide (100 microM; 17.3 +/- 4.7%) and the protein trafficking inhibitor brefeldin A (10 microM; 12.1 +/- 4.8%) but was unaffected by the transcription inhibitor actinomycin D (2 microM; 65.1 +/- 3.6%), which did, however, abolish upregulation of B1-kinin receptors in this preparation. 5. In conclusion, our findings indicate that activation-independent amino-terminal proteolysis of PARs stimulates selective recovery of endothelial cell PAR-2 responsiveness, which appears to be regulated by translation. Such a novel mechanism for the maintenance of responsiveness to enzymic PAR-2 activators may imply that these receptors play important roles in vascular homeostasis.

Two faces of orbital hematoma in intranasal (endoscopic) sinus surgery.

Orbital hematoma and blindness can occur during or after sinus surgery. All orbital hematomas in 3500 endoscopic sinus ethmoidectomies were identified and evaluated for type, treatment, and sequelae. Fifteen orbital hematomas were identified, with 1 case of temporary blindness and no cases of permanent blindness. Two types of orbital hematoma were identified-slow (venous) and fast (arterial)-which differ in management. The venous type results from penetration of the lamina papyracea and disruption of veins. The arterial hematoma is caused by anterior or posterior ethmoid artery injury. The treatment approach to each is different, with blindness more likely occurring from a fast (arterial) hematoma. Of the 2 types of orbital hematoma that can occur during sinus surgery, surgical decompression and hemorrhage control are more likely with the fast arterial hematoma, which has not been the subject of any prior presentation. Cause and management of each will be discussed.

A protective role for protease-activated receptors in the airways.

The protection of cells in the upper intestine against digestion by pancreatic trypsin depends on the prostanoid prostaglandin E2 (PGE2) and is mediated by protease-activated receptors in the epithelium. As the airway epithelium is morphologically similar and also expresses one of these receptors, PAR2, and is a major source of PGE2, we reasoned that bronchial epithelial PAR2 might also participate in prostanoid-dependent cytoprotection in the airways. Here we show that activation of PAR2, which co-localizes immunohistochemically with trypsin(ogen) in airway epithelium, causes the relaxation of airway preparations from mouse, rat, guinea-pig and humans by the release of a cyclooxygenase product from the epithelium. This physiological protective response in isolated airways also occurred in anaesthetized rats, where activation of PAR2 caused a marked and prolonged inhibition of bronchoconstriction. After desensitization of PAR2, the response to trypsin recovered rapidly by mechanisms dependent on de novo synthesis and trafficking of proteins. Our results indicate that trypsin released from the epithelium can initiate powerful bronchoprotection in the airways by activation of epithelial PAR2.

Endoscopic transsphenoidal biopsy of the sphenoid and clival mass.

Abnormalities of the clivus/skull base occur most commonly as a result of disease spread from adjacent structures, but can also occur from primary involvement of the clivus. Traditionally, definitive diagnosis was made by CT guided biopsy or craniotomy. However, lesions can occur in this area that are not amenable to CT guided biopsy or craniotomy. Endoscopic transsphenoidal surgery can provide a safe method for obtaining a clival biopsy, debulking of tumor tissue, or definitive treatment without the morbidity and mortality of a craniotomy. This study was designed to describe our experience with the endoscopic approach to the skull base and clivus via the sphenoid sinus. A series of seven patients underwent endoscopic transsphenoidal biopsy of a sphenoid clival lesion. All patients avoided anticipated craniotomy, and definitive pathology was obtained in five of six patients. In two cases, excisional biopsy proved to be therapeutic. There were no deaths, and major complications included one CSF leak and one intraoperative hemorrhage, both of which were controlled immediately. The experience gained with these patients demonstrates the feasibility and safety of this new application of endoscopic sinus surgery for the diagnosis and possible treatment of lesions of the sphenoid and clivus.

Continuous culture selection of bifidobacteria and lactobacilli from human faecal samples using fructooligosaccharide as selective substrate.

The human large intestine contains a large and diverse population of bacteria. Certain genera, namely Bifidobacterium and Lactobacillus, are thought to exert health-promoting effects. Prebiotics such as fructooligosaccharides (FOS) have been shown to stimulate the growth of endogenous bifidobacteria. In this study, changes of lactic acid producing bacteria in continuous culture fermentors (semi-defined, anaerobic medium containing 5 g 1(-1) FOS, dilution rate of 0.1 h-1, pH 5.5) were followed over a 21 d period after inoculation with blended human faeces from four healthy adults. Samples were also taken every 3 d for influent/effluent FOS, short chain fatty acid (SCFA), lactate and microbiological analyses. Results showed that SCFA concentrations decreased abruptly 1 d after inoculation while lactate concentrations increased. Classical methods of enumeration using selective media showed that the proportion of total culturable count represented by bifidobacteria and lactobacilli increased from 11.9% on day 1 to 98.1% on day 21. However, molecular methods using genus-specific 16S rRNA oligonucleotide probes indicated that the bifidobacterial population maintained a level between 10 and 20% of total 16S rRNA during the first 6 d and disappeared rapidly when the maximum concentration of lactate was reached. Lactobacilli, which were initially present in low numbers, increased until day 9 and remained at high levels (20-42% of total 16S rRNA) to day 21, with the exception of day 18. Although FOS has usually been regarded as a selective substrate for bifidobacteria, these observations suggest that: (1) lactobacilli are also able to use FOS, (2) lactobacilli can out-compete bifidobacteria in continuous culture at pH 5.2-5.4 when FOS is the primary carbon and energy source, and (3) bifidobacteria can grow faster on FOS than lactobacilli under controlled conditions.

Screening of sex workers in Turkey for Chlamydia trachomatis.

BACKGROUND: Increasing migration of sex workers across East European borders into Turkey has resulted in increased arrests of unregistered sex workers. There is concern regarding the prevalence of sexually transmitted diseases (STD) such as C. trachomatis in this unregulated group. OBJECTIVE: To measure the prevalence of C. trachomatis infection and selected related demographic and behavioral factors among registered and unregistered sex workers in Istanbul, Turkey. METHODS: In a cross-sectional study, the prevalence of C. trachomatis infection was studied by direct fluorescent antibody testing in 248 sex workers: 158 presented for routine medical screening and 90 who were arrested for lack of registration. All subjects were interviewed regarding demographic factors, sexual activity, and antibiotic and drug use. RESULTS: The overall C. trachomatis prevalence was 12.9% (12.0% registered and 14.4% unregistered). There was a strong association between never using condoms and chlamydia positivity (odds ratio 8.9 [95% confidence interval 3.7 to 21.6]). CONCLUSIONS: The high rate of C. trachomatis among all tested sex workers and the lack of regular condom use, particularly among unregistered sex workers, indicate that there is an urgent need for safe sex education and continued STD screening of unregistered sex workers.

PIP: Accelerating migration of unregistered sex workers from Eastern European countries to Turkey has produced alarm about the potential for increased sexually transmitted disease (STD) transmission. Licensed sex workers are routinely screened for STDs and given medical examinations. However, in Turkey, women with foreign citizenship are ineligible for licensing. This cross-sectional study measured the prevalence of Chlamydia trachomatis in 248 sex workers in Istanbul in 1993. 158 sex workers were enrolled when they presented for routine medical screening, while 90 (from Rumania) were arrested for lack of registration. The overall C. trachomatis prevalence, as detected by direct fluorescent antibody testing, was 12.9% (12.0% among registered and 14.4% among unregistered women); however, the fact that almost half these women reported recent self-prescribed antibiotic use suggests these rates are underestimates. When the analysis was restricted to the 84 women without recent antibiotic use, the C. trachomatis prevalence was 36.9%. There was a significant association between never using condoms and chlamydia infection (odds ratio, 8.9; 95% confidence interval, 3.7-21.6). These findings suggest a need for safe sex education and continued STD screening of sex workers in Turkey. Eligibility for registration, regardless of nationality, should be reconsidered for public health reasons.

Powered instrumentation in orbital and optic nerve decompression.

Powered instrumentation in orbital and optic nerve decompression is a helpful adjunct to performing safe, functional, and complete surgery. The microdebrider and the drill are the powered instruments most often used. Combined with endoscopic visualization, these tools provide appropriate drainage and decompression whether for orbital abscesses, Grave's ophthalmopathy, or optic nerve injury.