Continuous Variable Entanglement in an Optical Parametric Oscillator Based on a Nondegenerate Four Wave Mixing Process in Hot Alkali Atoms.

We present the measurement of entanglement between twin beams generated with a doubly resonant optical parameter oscillator (OPO) based on four-wave mixing in hot ^{85}Rb vapor above threshold. This is the first measurement of entanglement in an OPO with a χ^{(3)} media above threshold. We reconstruct the covariance matrix for several configurations and based on a full picture of the four side band mode state, we study entanglement between all possible bipartitions. We show a robust generation of entanglement with stronger generation for a specific pair of modes. For this system, we show that atomic density is a determinant factor for the generation and loss of quantum correlations. The generation of entangled fields with an atomic OPO operating close to atomic resonance of alkali atoms enables a natural integration into quantum networks.

Quantum Noise Correlations of an Optical Parametric Oscillator Based on a Nondegenerate Four Wave Mixing Process in Hot Alkali Atoms.

We present the first measurement of two-mode squeezing between the twin beams produced by a doubly resonant optical parameter oscillator (OPO) in an above threshold operation based on parametric amplification by nondegenerate four wave mixing with rubidium (^{85}Rb). We demonstrate a maximum intensity difference squeezing of -2.7 dB (-3.5 dB corrected for losses) with a pump power of 285 mW and an output power of 12 mW for each beam, operating close to the D1 line of Rb atoms. The use of open cavities combined with the high gain media can provide a strong level of noise compression and the access to new operation regimes that could not be explored by crystal based OPOs. The spectral bandwidth of the squeezed light is broadened by the cavity dynamics, and the squeezing level is robust for strong pump powers. Stable operation was obtained up to 4 times above the threshold. Moreover, operation of the OPO close to the atomic resonances of alkali atoms allows a natural integration into quantum networks, including structures such as quantum memories.

Tunable delay of Einstein-Podolsky-Rosen entanglement.

Entangled systems display correlations that are stronger than can be obtained classically. This makes entanglement an essential resource for a number of applications, such as quantum information processing, quantum computing and quantum communications. The ability to control the transfer of entanglement between different locations will play a key role in these quantum protocols and enable quantum networks. Such a transfer requires a system that can delay quantum correlations without significant degradation, effectively acting as a short-term quantum memory. An important benchmark for such systems is the ability to delay Einstein-Podolsky-Rosen (EPR) levels of entanglement and to be able to tune the delay. EPR entanglement is the basis for a number of quantum protocols, allowing the remote inference of the properties of one system (to better than its standard quantum limit) through measurements on the other correlated system. Here we show that a four-wave mixing process based on a double-lambda scheme in hot (85)Rb vapour allows us to obtain an optically tunable delay for EPR entangled beams of light. A significant maximum delay, of the order of the width of the cross-correlation function, is achieved. The four-wave mixing also preserves the quantum spatial correlations of the entangled beams. We take advantage of this property to delay entangled images, making this the first step towards a quantum memory for images.

Experimental generation of multiple quantum correlated beams from hot rubidium vapor.

Quantum correlations and entanglement shared among multiple quantum modes are important for both fundamental science and the future development of quantum technologies. This development will also require an efficient quantum interface between multimode quantum light sources and atomic ensembles, which makes it necessary to implement multimode quantum light sources that match the atomic transitions. Here, we report on such a source that provides a method for generating quantum correlated beams that can be extended to a large number of modes by using multiple four-wave mixing (FWM) processes in hot rubidium vapor. Experimentally, we show that two cascaded FWM processes produce strong quantum correlations between three bright beams but not between any two of them. In addition, the intensity-difference squeezing is enhanced with the cascaded system to -7.0±0.1 dB from the -5.5±0.1/-4.5±0.1 dB squeezing obtained with only one FWM process. One of the main advantages of our system is that as the number of quantum modes increases, so does the total degree of quantum correlations. The proposed method is also immune to phase instabilities due to its phase insensitive nature, can easily be extended to multiple modes, and has potential applications in the production of multiple quantum correlated images.

Noiseless optical amplifier operating on hundreds of spatial modes.

We implement a noiseless optical amplifier using a phase-sensitive four-wave mixing process in rubidium vapor. We observe performance near the quantum limit for this type of amplifier over a range of experimental parameters and show that the noise figure is always better than would be obtained with a phase-insensitive amplifier with the same gain. Additionally, we observe that the amplifier supports hundreds of spatial modes, making it possible to amplify complex two-dimensional spatial patterns with less than a 10% degradation of the input signal-to-noise ratio for gains up to 4.6. To confirm the multimode character of the amplifier, we study the noise figure as a function of spatially-varying losses. Additionally, we investigate the spatial resolution of the amplifier and show that it supports a range of spatial frequencies from 1.3 to more than 35 line pairs per millimeter.

Quantum correlated light beams from non-degenerate four-wave mixing in an atomic vapor: the D1 and D2 lines of 85Rb and 87Rb.

We present experimental results showing that quantum correlated light can be produced using non-degenerate, off-resonant, four-wave mixing (4WM) on both the D1 (795 nm) and D2 (780 nm) lines of (85)Rb and (87)Rb, extending earlier work on the D1 line of (85)Rb. Using this 4WM process in a hot vapor cell to produce bright twin beams, we characterize the degree of intensity-difference noise reduction below the standard quantum limit for each of the four systems. Although each system approximates a double-lambda configuration, differences in details of the actual level structure lead to varying degrees of noise reduction. The observation of quantum correlations on light produced using all four of these systems, regardless of their substructure, suggests that it should be possible to use other systems with similar level structures in order to produce narrow frequency, non-classical beams at a particular wavelength.

Study of gastrointestinal nematodes in Sicilian sheep and goats.

Parasitic gastroenteritis is one of the major causes of productivity loss in sheep and goats. This report records two studies of the helminth fauna from post-mortem examination. The first study, performed on the digestive tract of 72 sheep from a central part of Sicily in a high hill village (1,360 meters above sea level), between April 1996 and March 1997, showed an infection rate of 78%. The second study targeted goats from the western part of Sicily and showed an infection rate of 90%. For sheep, a total of 23 species of helminths were identified belonging to the family of Trichostrongyloidea, with the genera Haemonchus, Ostertagia (Teladorsagia), Trichostrongylus, Cooperia, and Nematodirus; Strongilolidea with the genera Oesophagostomum and Chabertia: Ancylostomidea with Bunostomum; and Tricuridea with Tricuris. Teladorsagia circumcincta was the most common in the sheep abomasum, Bunostomum trigonocephalum and Trichostrongylus spp. in the small intestine, and Chabertia ovina and Trichuris ovis in the large intestine. For goats, a total of 12 species were isolated in the abomasum with Teladorsagia circumcincta and Trichostrongylus axei the most common species. In the small intestine, five species were isolated and Trichostrongylus capricola was the dominant species. T. ovis and O. venulosum were dominant in large intestine and in the cecum. We also found species belonging to other ruminants such as O. ostertagi (in cattle) and S. kolchida and O. leptospicularis (in wild ruminants).

Distribution of the dipeptide transporter system along the gastrointestinal tract of rats based on absorption of a stable and specific probe, SQ-29852.

Peptidic drugs such as beta-lactam aminocephalosporin antibiotics (e.g., cephalexin) and the ACE inhibitors lisinopril, quinapril, and benzazepril are apparently absorbed, at least in part, by the intestinal dipeptide transporter system (DTS). Although many properties of the DTS have been elucidated, including isolation of the carrier protein, little is known about the distribution of this transporter along the gastrointestinal (GI) tract. The objectives of the present study were to (1) validate that SQ-29852 (a lysylproline ACE inhibitor) is a stable and specific probe for evaluation of the DTS in rats and (2) provide fundamental in vivo information on the distribution of the DTS along the GI tract of rats. Most of the previous studies that explored the location of the DTS typically involved either in vitro uptake or in situ disappearance of unstable or nonspecific probes. SQ-29852, on the other hand, is an ideal probe for evaluation of the DTS because it is chemically and metabolically stable and it is absorbed almost exclusively by the DTS. SQ-29852 appears to be a specific probe for the DTS because the dose-dependent reduction in absorption from about 60% to less than 8% (3 and 3000 mg/kg, respectively) suggests that at least 85% of an orally administered low dose of SQ-29852 is absorbed by a saturable process, which was shown previously to be the DTS. [14C]SQ-29852 was administered by gavage to intact rats and via an indwelling cannula in one of the following sections of the intestine: duodenum, jejunum, ileum and proximal colon (n = 4 for each site). On the basis of the recovery of [14C]SQ-29852 in urine, the DTS is apparently distributed throughout the entire GI tract of rats, including the proximal colon. The present results are consistent with previously reported results on the absorption of natural dipeptides in humans and rats and immunohistochemical evaluation in rats; however, they disagree with a recent report in humans with amoxicillin. This difference is discussed in terms of the specificity and stability of various drugs that have been used as probes of the DTS.

Prodrugs of BMS-183920: metabolism and permeability considerations.

The oral bioavailability of BMS-183920, a diacidic, potent angiotensin II receptor antagonist, is low in rats (approximately 11%). In vivo studies in bile duct-cannulated rats indicated that BMS-183920 was metabolically stable and that the low bioavailability was due to incomplete intestinal absorption. Five acyl-ester prodrugs were synthesized which were 5-15 times more permeable than BMS-183920 through Caco-2 cells. However, limited studies in rats indicated that the oral bioavailability of BMS-183920 was improved only 2-fold, in the best case. The lack of a substantial increase in bioavailability was apparently due to presystemic prodrug hydrolysis or metabolism via N-glucuronidation. Bioavailability of BMS-183920 after oral dosing of a tetrazole-ester prodrug averaged 37%, the most significant improvement within this prodrug series. Interestingly, in vitro studies indicated that the tetrazole-ester prodrug was a substrate for glucuronosyl transferase; however, its rate of bioactivation (hydrolysis) was sufficiently high to provide a substantial increase in bioavailability of BMS-183920. Therefore, while prodrug modification of BMS-183920 improved Caco-2 cell permeability and oral absorption in vivo, the relative extents of hydrolysis (bioactivation) vs metabolism of the prodrug determined whether a substantial improvement in bioavailability was achieved.

Benign fibrous histiocytoma of the small intestine in a cow.

A well circumscribed, firm nodule was found protruding from the duodenal wall of an adult cow at routine meat inspection. On the basis of morphological and immunophenotypic features, a diagnosis of benign fibrous histiocytoma (BFH) was established. Malignant fibrous histiocytoma has been reported previously in the cow, albeit rarely, but to the best of our knowledge this is the first recorded case of bovine intestinal BFH.

Low-noise amplification of a continuous-variable quantum state.

We present an experimental realization of a low-noise, phase-insensitive optical amplifier using a four-wave mixing interaction in hot Rb vapor. Performance near the quantum limit for a range of amplifier gains, including near unity, can be achieved. Such low-noise amplifiers are essential for so-called quantum cloning machines and are useful in quantum information protocols. We demonstrate that amplification and "cloning" of one half of a two-mode squeezed state is possible while preserving entanglement.

Generation of spatially broadband twin beams for quantum imaging.

We generate spatially multimode twin beams using 4-wave mixing in a hot atomic vapor in a phase-insensitive traveling-wave amplifier configuration. The far-field coherence area measured at 3.5 MHz is shown to be much smaller than the angular bandwidth of the process and bright twin images with independently quantum-correlated subareas can be generated with little distortion. The available transverse degrees of freedom form a high-dimensional Hilbert space that we use to produce quantum-correlated twin beams with finite orbital angular momentum.

Violation of the Cauchy-Schwarz inequality in the macroscopic regime.

We have observed a violation of the Cauchy-Schwarz inequality in the macroscopic regime by more than 8 standard deviations. The violation has been obtained while filtering out only the low-frequency noise of the quantum-correlated beams that results from the technical noise of the laser used to generate them. We use bright intensity-difference squeezed beams produced by four-wave mixing as the source of the correlated fields. We also demonstrate that squeezing does not necessarily imply a violation of the Cauchy-Schwarz inequality.

Delocalized correlations in twin light beams with orbital angular momentum.

We generate intensity-difference-squeezed Laguerre-Gauss twin beams of light carrying orbital angular momentum by using four-wave mixing in a hot atomic vapor. The conservation of orbital angular momentum in the four-wave mixing process is studied as well as the spatial distribution of the quantum correlations obtained with different configurations of orbital angular momentum. Intensity-difference squeezing of up to -6.7 dB is demonstrated with beams carrying orbital angular momentum. Delocalized spatial correlations between the twin beams are observed.

Evaluation of new culture media for rapid detection and isolation of salmonellae in foods.

Conventional methods for Salmonella detection in foods can require up to 6 and at least 4 days. We have observed that the total analysis time can be reduced to 48 h by using Salmosyst broth as a liquid medium for both preenrichment and selective enrichment and Rambach agar (RA), a new selective plate medium. In samples of artificially contaminated ground beef Salmonella enteritidis was detected at a concentration of 0.4 CFU/g (10 CFU/25 g) by both a conventional method and the new method. Of 519 samples of foods for sale, 38 were Salmonella positive by both methods while 471 were negative. Nine samples which were negative by the conventional method were positive by the Salmosyst-RA method, while one sample positive by the first method was negative by the last. Therefore, the Salmosyst-RA method showed 97.9% sensitivity compared with the 81.2% sensitivity of the conventional method. The new method was also highly specific (98% specificity) in presumptive identification of Salmonella colonies. Furthermore, a 6-h preenrichment in Salmosyst broth has been proved sufficient for the repair of heat-injured Salmonella cells and for subsequent recovery by selective enrichment. In conclusion, the Salmosyst-RA method shows several advantages over both conventional and rapid noncultural methods: (i) only two media are required instead of the five media for conventional methods; (ii) in real time it is comparable to other rapid noncultural methods, which require 30 to 31 h; (iii) it is highly sensitive and specific; and (iv) it allows the isolation of Salmonella strains which can be characterized by appropriate phenotypic and genotypic typing methods for epidemiological investigations.

Application of structure-metabolism relationships in the identification of a selective endothelin A antagonist, BMS-193884, with favourable pharmacokinetic properties.

1. Based on binding affinity, 2'-amino-N-(3,4-dimethyl-5-isoxazolyl)-4'-(2-methylpropyl)[1,1'-biphenyl]-2-sulfonamide (2) was identified as an initial lead in a programme to identify selective endothelin (ET) receptor antagonists. However, the compound was extensively metabolized in preclinical animal species and human in vitro systems due to oxidative biotransformation. 2. To optimize this structural class, the site of metabolism of 2 was determined. This allowed for focussed structure-activity and structure-metabolism studies aimed at finding more metabolically stable analogues that maintained potency. New analogues were screened for their ET binding characteristics and their stability in rat and human liver microsomes. 3. The use of the microsomal stability screen was tested by the determination of the pharmacokinetic parameters of select analogues. A good correlation was found between reduced rates of rat microsomal metabolism and reduced clearance in the rat. 4. N-(3,4-dimethyl-5-isoxazolyl)-4'-(2-oxazolyl)[1,1'-biphenyl]-2-sulfonamide (3) was identified as an analogue with improved in vitro properties and further studies revealed that the compound had improved pharmacokinetic properties. 5. N-[[2'-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]-2-yl]methyl]acetamide (4) was subsequently identified as a compound with superior in vitro properties compared with compound 3, but when tested in vivo it had a substantially increased rate of clearance. Further studies demonstrated that the clearance of this closely related structural analogue was not dictated by metabolic processes, but was mediated by transport-mediated direct biliary excretion. 6. The utility of screening for in vitro liver microsomal stability as part of the lead optimization process for compounds with metabolic liabilities was shown. It was also shown that relatively small molecular changes can dramatically change the disposition of closely related analogues and care must be used when screening for a single property.

Modelling the distribution of outbreaks and Culicoides vectors in Sicily: towards predictive risk maps for Italy.

Vector (911 light-trap catches from 269 sites) and serological surveillance data were obtained during recent bluetongue (BT) outbreaks in Sicily. The distributions of Culicoides vectors are compared with that of bluetongue virus (BTV) to determine the relative role of different vectors in BTV transmission in Sicily. The 'best' climatic predictors of distribution for each vector species were selected from 40 remotely-sensed variables and altitude at a 1 km spatial resolution using discriminant analysis. These models were used to predict species presence in unsampled pixels across Italy. Although Culicoides imicola, the main European vector, was found in only 12% of sites, there was close correspondence between its spatial distribution and that of the 2000 and 2001 outbreaks. All three candidate vectors C. pulicaris, C. newsteadi and C. obsoletus group were widespread across 2002 outbreak sites but C. newsteadi was significantly less prevalent in outbreak versus non-outbreak sites in Messina and BTV has been isolated from wild-caught adults of both C. pulicaris and C. obsoletus in Italy. The yearly distribution and intensity of outbreaks is attributable to the distribution and abundance of the vectors operating in each year. Outbreaks were few and coastal in 2000 and 2001 due to the low abundance and prevalence of the vector, C. imicola. They were numerous and widespread in 2002, following hand-over of the virus to more prevalent and abundant novel vector species, C. pulicaris and C. obsoletus. Climatic determinants of distribution were species-specific, with those of C. obsoletus group and C. newsteadi predicted by temperature variables, and those of C. pulicaris and C. imicola determined mainly by normalised difference vegetation index (NDVI), a variable correlated with soil moisture, vegetation biomass and productivity. The predicted continuous presence of C. pulicaris along the Appenine mountains, from north to south Italy, suggests BTV transmission may be possible in a large proportion of this region and that seasonal transhumance between C. imicola-free areas should not generally be considered safe. Future distribution models for C. imicola in Sicily should include non-climatic environmental variables that may influence breeding site suitability such as soil type.