Non-Gaussian Correlations in the Steady State of Driven-Dissipative Clouds of Two-Level Atoms.

We report experimental measurements of the second-order coherence function g^{(2)}(τ) of the light emitted by a laser-driven dense ensemble of ^{87}Rb atoms. We observe a clear departure from the Siegert relation valid for Gaussian chaotic light. Measuring intensity and first-order coherence, we conclude that the violation is not due to the emergence of a coherent field. This indicates that the light obeys non-Gaussian statistics, stemming from non-Gaussian correlations in the atomic medium. More specifically, the steady state of this driven-dissipative many-body system sustains high-order correlations in the absence of first-order coherence. These findings call for new theoretical and experimental explorations to uncover their origin, and they open new perspectives for the realization of non-Gaussian states of light.

Fermionic Correlation Functions from Randomized Measurements in Programmable Atomic Quantum Devices.

We provide an efficient randomized measurement protocol to estimate two- and four-point fermionic correlations in ultracold atom experiments. Our approach is based on combining random atomic beam splitter operations, which can be realized with programmable optical landscapes, with high-resolution imaging systems such as quantum gas microscopes. We illustrate our results in the context of the variational quantum eigensolver algorithm for solving quantum chemistry problems.

Observation of 1/k

We measure the momentum density in a Bose-Einstein condensate (BEC) with dilute spin impurities after an expansion in the presence of interactions. We observe tails decaying as 1/k^{4} at large momentum k in the condensate and in the impurity cloud. These algebraic tails originate from the impurity-BEC interaction, but their amplitudes greatly exceed those expected from two-body contact interactions at equilibrium in the trap. Furthermore, in the absence of impurities, such algebraic tails are not found in the BEC density measured after the interaction-driven expansion. These results highlight the key role played by impurities when present, a possibility that had not been considered in our previous work [Chang et al., Phys. Rev. Lett. 117, 235303 (2016)PRLTAO0031-900710.1103/PhysRevLett.117.235303]. Our measurements suggest that these unexpected algebraic tails originate from the nontrivial dynamics of the expansion in the presence of impurity-bath interactions.

Synthesis and structure-activity relationship studies of original cyclic diadenosine derivatives as nanomolar inhibitors of NAD kinase from pathogenic bacteria.

Nicotinamide adenine dinucleotide kinases (NAD kinases) are essential and ubiquitous enzymes involved in the production of NADP(H) which is an essential cofactor in many metabolic pathways. Targeting NAD kinase (NADK), a rate limiting enzyme of NADP biosynthesis pathway, represents a new promising approach to treat bacterial infections. Previously, we have produced the first NADK inhibitor active against staphylococcal infection. From this linear di-adenosine derivative, namely NKI1, we designed macrocyclic analogues. Here, we describe the synthesis and evaluation of an original series of cyclic diadenosine derivatives as NADK inhibitors of two pathogenic bacteria, Listeria monocytogenes and Staphylococcus aureus. The nature and length of the link between the two adenosine units were examined leading to sub-micromolar inhibitors of NADK1 from L. monocytogenes, including its most potent in vitro inhibitor reported so far (with a 300-fold improvement compared to NKI1).

Structure-based design, synthesis and biological evaluation of a NAD+ analogue targeting Pseudomonas aeruginosa NAD kinase.

Multidrug resistance is a major public health problem that requires the urgent development of new antibiotics and therefore the identification of novel bacterial targets. The activity of nicotinamide adenine dinucleotide kinase, NADK, is essential in all bacteria tested so far, including many human pathogens that display antibiotic resistance leading to the failure of current treatments. Inhibiting NADK is therefore a promising and innovative antibacterial strategy since there is currently no drug on the market targeting this enzyme. Through a fragment-based drug design approach, we have recently developed a NAD+ -competitive inhibitor of NADKs, which displayed in vivo activity against Staphylococcus aureus. Here, we show that this compound, a di-adenosine derivative, is inactive against the NADK enzyme from the Gram-negative bacteria Pseudomonas aeruginosa (PaNADK). This lack of activity can be explained by the crystal structure of PaNADK, which was determined in complex with NADP+ in this study. Structural analysis led us to design and synthesize a benzamide adenine dinucleoside analogue, active against PaNADK. This novel compound efficiently inhibited PaNADK enzymatic activity in vitro with a Ki of 4.6 µm. Moreover, this compound reduced P. aeruginosa infection in vivo in a zebrafish model.

Certifying the Adiabatic Preparation of Ultracold Lattice Bosons in the Vicinity of the Mott Transition.

We present a joint experimental and theoretical analysis to assess the adiabatic experimental preparation of ultracold bosons in optical lattices aimed at simulating the three-dimensional Bose-Hubbard model. Thermometry of lattice gases is realized from the superfluid to the Mott regime by combining the measurement of three-dimensional momentum-space densities with ab initio quantum Monte Carlo (QMC) calculations of the same quantity. The measured temperatures are in agreement with isentropic lines reconstructed via QMC for the experimental parameters of interest, with a conserved entropy per particle of S/N=0.8(1)k_{B}. In addition, the Fisher information associated with this thermometry method shows that the latter is most accurate in the critical regime close to the Mott transition, as confirmed in the experiment. These results prove that equilibrium states of the Bose-Hubbard model-including those in the quantum-critical regime above the Mott transition-can be adiabatically prepared in cold-atom apparatus.

Hanbury Brown and Twiss Bunching of Phonons and of the Quantum Depletion in an Interacting Bose Gas.

We report the realization of a Hanbury Brown and Twiss (HBT)-like experiment with a gas of interacting bosons at low temperatures. The low-temperature regime is reached in a three-dimensional optical lattice and atom-atom correlations are extracted from the detection of individual metastable helium atoms after a long free fall. We observe, in the noncondensed fraction of the gas, a HBT bunching whose properties strongly deviate from the HBT signals expected for noninteracting bosons. In addition, we show that the measured correlations reflect the peculiar quantum statistics of atoms belonging to the quantum depletion and of the Bogoliubov phonons, i.e., of collective excitations of the many-body quantum state. Our results demonstrate that atom-atom correlations provide information about the quantum state of interacting particles, extending the interest of HBT-like experiments beyond the case of noninteracting particles.

New Chemical Probe Targeting Bacterial NAD Kinase.

Nicotinamide adenine dinucleotide (NAD) kinases are essential and ubiquitous enzymes involved in the tight regulation of NAD/nicotinamide adenine dinucleotide phosphate (NADP) levels in many metabolic pathways. Consequently, they represent promising therapeutic targets in cancer and antibacterial treatments. We previously reported diadenosine derivatives as NAD kinase inhibitors with bactericidal activities on Staphylococcus aureus. Among them, one compound (namely NKI1) was found effective in vivo in a mouse infection model. With the aim to gain detailed knowledge about the selectivity and mechanism of action of this lead compound, we planned to develop a chemical probe that could be used in affinity-based chemoproteomic approaches. Here, we describe the first functionalized chemical probe targeting a bacterial NAD kinase. Aminoalkyl functional groups were introduced on NKI1 for further covalent coupling to an activated SepharoseTM matrix. Inhibitory properties of functionalized NKI1 derivatives together with X-ray characterization of their complexes with the NAD kinase led to identify candidate compounds that are amenable to covalent coupling to a matrix.

From Substrate to Fragments to Inhibitor Active In Vivo against Staphylococcus aureus.

Antibiotic resistance is a worldwide threat due to the decreasing supply of new antimicrobials. Novel targets and innovative strategies are urgently needed to generate pathbreaking drug compounds. NAD kinase (NADK) is essential for growth in most bacteria, as it supports critical metabolic pathways. Here, we report the discovery of a new class of antibacterials that targets bacterial NADK. We generated a series of small synthetic adenine derivatives to screen those harboring promising substituents in order to guide efficient fragment linking. This led to NKI1, a new lead compound inhibiting NADK that showed in vitro bactericidal activity against Staphylococcus aureus. In a murine model of infection, NKI1 restricted survival of the bacteria, including methicillin-resistant S. aureus. Collectively, these findings identify bacterial NADK as a potential drug target and NKI1 as a lead compound in the treatment of staphylococcal infections.

Tan's Contact for Trapped Lieb-Liniger Bosons at Finite Temperature.

The universal Tan relations connect a variety of microscopic features of many-body quantum systems with two-body contact interactions to a single quantity, called the contact. The latter has become pivotal in the description of quantum gases. We provide a complete characterization of the Tan contact of the harmonically trapped Lieb-Liniger gas for arbitrary interactions and temperature. Combining thermal Bethe ansatz, local-density approximation, and exact quantum Monte Carlo calculations, we show that the contact is a universal function of only two scaling parameters, and determine the scaling function. We find that the temperature dependence of the contact, or equivalently the interaction dependence of the entropy, displays a maximum. The presence of this maximum provides an unequivocal signature of the crossover to the fermionized regime and it is accessible in current experiments.

High intensity focused ultrasound cyclocoagulation in dogs with primary glaucoma: a preliminary study.

The objective was to assess the effect of high intensity focused ultrasound (HIFU) on intraocular pressure (IOP) in dogs with primary glaucoma (PG). Seven dogs (13 eyes) presenting with PG as diagnosed by a raised IOP (> 20 mm Hg) associated with consistent gonioscopy and ultrasound biomicroscopy of the ciliary cleft, with no other ocular disease. Patients were divided into 3 groups, corresponding to their pre-operative IOP (group 1 ranging from 21 to 30 mm Hg, group 2 from 31 to 40 and group 3 for 40 and above). Ciliary process sonication was achieved with a probe containing one high-frequency transducer operating at 21 MHz during 5 seconds. Six sites were treated in patients from group 1, 8 in group 2, 10 in group 3, under general anesthesia. Post-operative treatment consisted of systemic meloxicam and topical carbonic anhydrase inhibitors, beta-blockers and prostaglandins analogues. No intraoperative complications were observed. Conjunctival hyperaemia occurred in eyes from group 2 (66%) and 3 (100%). Conjunctival burns were visible in 2 patients from group 3. One patient from group 3 experienced a hypertensive spike during the first hours post-op with associated pain. The hypotensive effect of HIFU was observed in all groups. Normotensive IOP (≤20 mm Hg) was reached in all patients until the last recheck at 6 months post op. Despite the small number of patients included in the study, HIFU appears to be a promising option for the management of PG in dogs.

Impacts of Contracted Endodontic Cavities on Primary Root Canal Curvature Parameters in Mandibular Molars.

INTRODUCTION: The purpose of this study was to provide information regarding the debate on contracted endodontic cavities (CECs); their impacts on angle, location, and radius of the primary canal curvature (PCC) were assessed in type IV mesial root canals of mandibular molars at different stages of instrumentation. Impacts on treatment time were also assessed. METHODS: Twenty-four teeth were matched by radiographic and micro-computed tomographic criteria and accessed via CECs (CEC, n = 12) or nonextended traditional endodontic cavities (TECs, n = 12). PCC parameters were radiographically determined using a repositioning apparatus before glide path preparation (PI), after glide path preparation, and after final instrumentation (FI). Instrumentation was performed with PathFiles (13/.02, 16/.02; Dentsply Maillefer, Ballaigues, Switzerland) and ProFile Vortex files (Dentsply Tulsa Dental Specialties, Tulsa, OK) to size 30/.04 at the working length under copious irrigation. Changes in PCC were measured with ImageJ (National Institutes of Health, Bethesda, MD). The instrumentation time was recorded. Data were analyzed with 2-way repeated measures analysis of variance (α < .05) and Tukey honest significant difference tests. RESULTS: A significant (P < .001) decrease in the mean angle and increase in the mean radius were detected at each instrumentation stage for both CECs (angle: PI = 42.57°± 8.00°, FI = 32.61°± 5.17°; radius: PI = 6.48 ± 1.81 mm, FI = 10.55 ± 1.48 mm) and TECs (angle: PI = 38.80°± 7.15°, FI = 30.08°± 6.99°; radius: PI = 6.97 ± 2.31 mm, FI = 11.01 ± 2.20 mm). PCC location shifted apically (P < .001). Changes in PCC parameters did not differ significantly between CECs and TECs (P > .05). The treatment time was significantly (P < .0001) longer for CECs (83.17 ± 6.71 minutes) than for TECs (33.18 ± 9.20 minutes). CONCLUSIONS: Instrumentation of curved mesial canals reduced the severity and abruptness of PCC and shifted the PCC location apically similarly in mandibular molars with CECs and those with nonextended TECs. The extended treatment time with CEC merits consideration when debating CECs versus TECs.

Quantum Depletion of a Homogeneous Bose-Einstein Condensate.

We measure the quantum depletion of an interacting homogeneous Bose-Einstein condensate and confirm the 70-year-old theory of Bogoliubov. The observed condensate depletion is reversibly tunable by changing the strength of the interparticle interactions. Our atomic homogeneous condensate is produced in an optical-box trap, the interactions are tuned via a magnetic Feshbach resonance, and the condensed fraction is determined by momentum-selective two-photon Bragg scattering.

Removal of calcium hydroxide from Weine Type II systems using photon-induced photoacoustic streaming, passive ultrasonic, and needle irrigation: a microcomputed tomography study

ABSTRACT Objective This study compared the effectiveness of Er:YAG laser-activated irrigation (PIPS), passive ultrasonic irrigation (PUI) with EndoUltra and standard needle irrigation (SNI) in the removal of calcium hydroxide [Ca(OH)2] from the mesial roots of Weine Type II mandibular molars. Material and Methods Thirty mandibular molars were screened by µCT for the presence of mesial roots with complex intra-canal anatomy and a common apical foramen. The teeth were enlarged to a standardized 25/.06 preparation and filled with Ca(OH)2 paste. Specimens were divided into three groups (n=10) according to the technique used for Ca(OH)2 removal: PIPS, at 15 Hz and 20 mJ using a 9 mm long, 600 µm diameter tip; PUI using a 15/.02 tip; and SNI (30 Ga. side-vented needle). Equal volumes of 8.25% NaOCl and 17% EDTA were used in all groups. µCT was used to measure the initial amount of Ca(OH)2 present and to assess the residual volume of Ca(OH)2 following each irrigation protocol. Data were analyzed using Tukey HSD and Kruskal-Wallis tests (α=5%). Results The mean volume of Ca(OH)2 before removal was significantly higher in the coronal third than in the middle and apical third (p<0.001). Ca(OH)2 was similarly removed from the coronal and middle thirds with the three methods used (p>0.05). PIPS (median 0%; IQR: 0-0) showed significant higher Ca(OH)2 removal in the apical third than PUI (median 100%, IQR: 85-100) and SNI (median 47%; IQR: 16-72) (p<0.001). Conclusions PIPS laser-activation was more effective for the removal of Ca(OH)2 from mesial roots of mandibular molars with Weine Type II canal configurations than PUI with EndoUltra and SNI.

Removal of calcium hydroxide from Weine Type II systems using photon-induced photoacoustic streaming, passive ultrasonic, and needle irrigation: a microcomputed tomography study.

OBJECTIVE: This study compared the effectiveness of Er:YAG laser-activated irrigation (PIPS), passive ultrasonic irrigation (PUI) with EndoUltra and standard needle irrigation (SNI) in the removal of calcium hydroxide [Ca(OH)2] from the mesial roots of Weine Type II mandibular molars. MATERIAL AND METHODS: Thirty mandibular molars were screened by µCT for the presence of mesial roots with complex intra-canal anatomy and a common apical foramen. The teeth were enlarged to a standardized 25/.06 preparation and filled with Ca(OH)2 paste. Specimens were divided into three groups (n=10) according to the technique used for Ca(OH)2 removal: PIPS, at 15 Hz and 20 mJ using a 9 mm long, 600 µm diameter tip; PUI using a 15/.02 tip; and SNI (30 Ga. side-vented needle). Equal volumes of 8.25% NaOCl and 17% EDTA were used in all groups. µCT was used to measure the initial amount of Ca(OH)2 present and to assess the residual volume of Ca(OH)2 following each irrigation protocol. Data were analyzed using Tukey HSD and Kruskal-Wallis tests (α=5%). RESULTS: The mean volume of Ca(OH)2 before removal was significantly higher in the coronal third than in the middle and apical third (p<0.001). Ca(OH)2 was similarly removed from the coronal and middle thirds with the three methods used (p>0.05). PIPS (median 0%; IQR: 0-0) showed significant higher Ca(OH)2 removal in the apical third than PUI (median 100%, IQR: 85-100) and SNI (median 47%; IQR: 16-72) (p<0.001). CONCLUSIONS: PIPS laser-activation was more effective for the removal of Ca(OH)2 from mesial roots of mandibular molars with Weine Type II canal configurations than PUI with EndoUltra and SNI.

Sarcococca Blight: Use of Whole-Genome Sequencing for Fungal Plant Disease Diagnosis.

Early and accurate diagnosis of new plant pathogens is vital for the rapid implementation of effective mitigation strategies and appropriate regulatory responses. Most commonly, pathogen identification relies on morphology and DNA marker analysis. However, for new diseases, these approaches may not be sufficient for precise diagnosis. In this study, we used whole-genome sequencing (WGS) to identify the causal agent of a new disease affecting Sarcococca hookeriana (sarcococca). Blight symptoms were observed on sarcococca and adjacent Buxus sempervirens (boxwood) plants in Maryland during 2014. Symptoms on sarcococca were novel, and included twig dieback and dark lesions on leaves and stems. A Calonectria sp. was isolated from both hosts and used to fulfill Koch's postulates but morphology and marker sequence data precluded species-level identification. A 51.4-Mb WGS was generated for the two isolates and identified both as Calonectria pseudonaviculata. A single-nucleotide polymorphism at a noncoding site differentiated between the two host isolates. These results indicate that the same C. pseudonaviculata genotype has the ability to induce disease on both plant species. This study marks the first application of WGS for fungal plant pathogen diagnosis and demonstrates the power of this approach to rapidly identify causal agents of new diseases.

Micro-Computed Tomographic Evaluation of the Influence of Root Canal System Landmarks on Access Outline Forms and Canal Curvatures in Mandibular Molars.

INTRODUCTION: This study investigated the influence of anatomic root canal system landmarks on access outline forms of mandibular molars and correlated these to the theoretical distance of orifice relocation and changes in canal primary curvature. METHODS: Thirty relatively calcified human mandibular molars were selected and examined by micro-computed tomographic imaging. Three-dimensional volume reconstructions were made, root canal system landmarks identified, and plotted: canal orifices, canal position at the furcation level, and pulp horn location. Each landmark was separately projected onto the occlusal surface, and 3 access designs were respectively proposed: (1) minimally invasive, (2) straight-line furcation, and (3) straight-line radicular. For each access design, the theoretical distance of orifice relocation and canal primary curvature were determined. Data were submitted to 2-way repeated measures analysis of variance (α < 0.05). RESULTS: The orifice relocation distance required to obtain each type of access outline was greater for radicular-based accesses (0.97 ± 0.32 mm) than for furcation accesses (0.52 ± 0.30 mm, P < .001) and resulted in a greater change in canal primary curvature (P < .001; 15.9° ± 4.6° and 9.4° ± 4.3°, respectively). The canal primary curvature for each access outline type was statistically different from each other (P < .0001), whereas the minimally invasive access showed the highest mean angle (40.1° ± 8.4°) followed by the straight-line furcation (30.7° ± 7.5°) and the straight-line radicular accesses (24.2° ± 8.4°). CONCLUSIONS: The use of different landmarks to establish access outline designs affected the primary angle of curvature in relatively calcified mandibular molars.

Contribution of inertial cavitation in the enhancement of in vitro transscleral drug delivery.

In ocular drug delivery, the sclera is a promising pathway for administering drugs to both the anterior and posterior segments of the eye. Due to the low permeability of the sclera, however, efficient drug delivery is challenging. In this study, pulsed ultrasound (US) was investigated as a potential method for enhancing drug delivery to the eye through the sclera. The permeability of rabbit scleral tissue to a model drug compound, sodium fluorescein, was measured after US-irradiation at 1.1 MHz using time-averaged acoustic powers of 0.5-5.4 W (6.8-12.8 MPa peak negative pressure), with a fixed duty cycle of 2.5% for two different pulse repetition frequencies of 100 and 1000 Hz. Acoustic cavitation activity was measured during exposures using a passive cavitation detector and was used to quantify the level of bubble activity. A correlation between the amount of cavitation activity and the enhancement of scleral permeability was demonstrated with a significant enhancement in permeability of US exposed samples compared to controls. Transmission electron microscopy showed no evidence of significant alteration in viability of tissue exposed to US exposures. A pulsed US protocol designed to maximum cavitation activity may therefore be a viable method for enhancing drug delivery to the eye.

Elimination of intracanal tissue and debris through a novel laser-activated system assessed using high-resolution micro-computed tomography: a pilot study.

INTRODUCTION: Laser-activated irrigation to remove organic debris from canal isthmuses was investigated using x-ray microfocus computed tomographic imaging. METHODS: A total of 14 extracted human mandibular molars were used. The mesial canals were prepared using a standardized instrumentation protocol. Two groups (n = 7) underwent final irrigation using either standard needle irrigation (SNI) or photon-induced photoacoustic streaming (PIPS). After enlarging canals to 30/.06, canal volumes were reconstructed from micro-computed tomographic scans before and after irrigation to assess removal of organic tissue and inorganic debris by quantitative analysis of the superimposed volumes. Comparisons of the volumes were made using 2-way analysis of variance and Tukey method, with statistical differences considered significant at the alpha = 0.05 level. RESULTS: Debris removal and an increase in root canal system volume for the laser-activated PIPS group was more significant (P < .001) than for the SNI group (P = .04). Irrigation using PIPS increased the canal volume and eliminated debris from the canal system 2.6 times greater than SNI. CONCLUSIONS: Eliminating debris from complex canal spaces found in mandibular molars was achieved at a significantly greater level using laser-activated PIPS irrigation compared with SNI.