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.

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.

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.

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.

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.

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.

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.

Direct observation of Anderson localization of matter waves in a controlled disorder.

In 1958, Anderson predicted the localization of electronic wavefunctions in disordered crystals and the resulting absence of diffusion. It is now recognized that Anderson localization is ubiquitous in wave physics because it originates from the interference between multiple scattering paths. Experimentally, localization has been reported for light waves, microwaves, sound waves and electron gases. However, there has been no direct observation of exponential spatial localization of matter waves of any type. Here we observe exponential localization of a Bose-Einstein condensate released into a one-dimensional waveguide in the presence of a controlled disorder created by laser speckle. We operate in a regime of pure Anderson localization, that is, with weak disorder-such that localization results from many quantum reflections of low amplitude-and an atomic density low enough to render interactions negligible. We directly image the atomic density profiles as a function of time, and find that weak disorder can stop the expansion and lead to the formation of a stationary, exponentially localized wavefunction-a direct signature of Anderson localization. We extract the localization length by fitting the exponential wings of the profiles, and compare it to theoretical calculations. The power spectrum of the one-dimensional speckle potentials has a high spatial frequency cutoff, causing exponential localization to occur only when the de Broglie wavelengths of the atoms in the expanding condensate are greater than an effective mobility edge corresponding to that cutoff. In the opposite case, we find that the density profiles decay algebraically, as predicted in ref. 13. The method presented here can be extended to localization of atomic quantum gases in higher dimensions, and with controlled interactions.

Leveraging artificial intelligence in vaccine development: A narrative review.

Vaccine development stands as a cornerstone of public health efforts, pivotal in curbing infectious diseases and reducing global morbidity and mortality. However, traditional vaccine development methods are often time-consuming, costly, and inefficient. The advent of artificial intelligence (AI) has ushered in a new era in vaccine design, offering unprecedented opportunities to expedite the process. This narrative review explores the role of AI in vaccine development, focusing on antigen selection, epitope prediction, adjuvant identification, and optimization strategies. AI algorithms, including machine learning and deep learning, leverage genomic data, protein structures, and immune system interactions to predict antigenic epitopes, assess immunogenicity, and prioritize antigens for experimentation. Furthermore, AI-driven approaches facilitate the rational design of immunogens and the identification of novel adjuvant candidates with optimal safety and efficacy profiles. Challenges such as data heterogeneity, model interpretability, and regulatory considerations must be addressed to realize the full potential of AI in vaccine development. Integrating emerging technologies, such as single-cell omics and synthetic biology, promises to enhance vaccine design precision and scalability. This review underscores the transformative impact of AI on vaccine development and highlights the need for interdisciplinary collaborations and regulatory harmonization to accelerate the delivery of safe and effective vaccines against infectious diseases.

Mild hypothermia during global cardiac ischemia opens a window of opportunity to develop heart donation after cardiac death.

Although heart donation after cardiac death (DCD) could greatly improve graft availability, concerns regarding warm ischemic damage typically preclude transplantation. Improving tolerance to warm ischemia may thus open a window of opportunity for DCD hearts. We investigated the hypothesis that, compared with normothermia, mild hypothermia (32° C) initiated after ischemic onset improves cardiac functional recovery upon reperfusion. Isolated, working hearts from adult, male Wistar rats underwent global, no-flow ischemia, and reperfusion (n = 28). After ischemic onset, temperature was maintained at either 37° C for 20 or 30 min or reduced to 32° C for 40, 50, or 60 min. Recovery was measured after 60-min reperfusion. Following normothermic ischemia, recovery of rate-pressure product (RPP; per cent of preischemic value) was almost complete after 20-min ischemia (97 ± 9%), whereas no recovery was detectable after 30-min ischemia. After mildly hypothermic ischemia (32° C), RPP also recovered well after 40 min (86 ± 4%). Markers of metabolism and necrosis were similar in 37° C/20 min and 32° C/40 min groups. Simple reduction in cardiac temperature by a few degrees after the onset of global ischemia dramatically prolongs the interval during which the heart remains resistant to functional deterioration. Preservation of hemodynamic function is associated with improved metabolic recovery and reduced necrosis. The application of mild hypothermia may be a simple first step towards development of clinical protocols for DCD heart recovery.

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.

Conditional GEE for recurrent event gap times.

This paper deals with the analysis of recurrent event data subject to censored observation. Using a suitable adaptation of generalized estimating equations for longitudinal data, we propose a straightforward methodology for estimating the parameters indexing the conditional means and variances of the process interevent (i.e. gap) times. The proposed methodology permits the use of both time-fixed and time-varying covariates, as well as transformations of the gap times, creating a flexible and useful class of methods for analyzing gap-time data. Censoring is dealt with by imposing a parametric assumption on the censored gap times, and extensive simulation results demonstrate the relative robustness of parameter estimates even when this parametric assumption is incorrect. A suitable large-sample theory is developed. Finally, we use our methods to analyze data from a randomized trial of asthma prevention in young children.

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.

Protein dynamics and stability: the distribution of atomic fluctuations in thermophilic and mesophilic dihydrofolate reductase derived using elastic incoherent neutron scattering.

The temperature dependence of the dynamics of mesophilic and thermophilic dihydrofolate reductase is examined using elastic incoherent neutron scattering. It is demonstrated that the distribution of atomic displacement amplitudes can be derived from the elastic scattering data by assuming a (Weibull) functional form that resembles distributions seen in molecular dynamics simulations. The thermophilic enzyme has a significantly broader distribution than its mesophilic counterpart. Furthermore, although the rate of increase with temperature of the atomic mean-square displacements extracted from the dynamic structure factor is found to be comparable for both enzymes, the amplitudes are found to be slightly larger for the thermophilic enzyme. Therefore, these results imply that the thermophilic enzyme is the more flexible of the two.

MGlu5 antagonism impairs exploration and memory of spatial and non-spatial stimuli in rats.

Metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in memory processing in some but not all learning tasks. The reason why this receptor is involved in some tasks but not in others remains to be determined. The present experiments using rats examined effects of the mGlu5-antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP)--applied systemically i.p. (1-10mg/kg) or bilaterally into the prelimbic cortex (1-10 microg)---on the ability of rats to explore and remember new stimuli. A cross-maze, open field, and object recognition task were used to evaluate exploration and memory and it was found that: (1) locomotion during exploration of spatial environments and exploration time at novel objects were reduced by i.p. but not by prelimbic administration of MPEP, (2) spatial short-term memory was impaired in cross-maze and object discrimination was reduced after both types of administration, (3) long-term retention of spatial conditioning in the cross-maze was inhibited after i.p. applications which (4) also inhibited spontaneous alternation performance during maze-exploration. Reduced exploratory locomotion and exploration time after i.p. injections may have contributed to the observed retention impairments. However, the fact that prelimbic administration of MPEP inhibited retention without reducing exploration shows that memory formation was also impacted directly by prelimbic mGlu5 in both spatial and non-spatial learning.

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.