Observation of first and second sound in a BKT superfluid.

Superfluidity in its various forms has been of interest since the observation of frictionless flow in liquid helium II1,2. In three spatial dimensions it is conceptually associated with the emergence of long-range order at a critical temperature. One of the hallmarks of superfluidity, as predicted by the two-fluid model3,4 and observed in both liquid helium5 and in ultracold atomic gases6,7, is the existence of two kinds of sound excitation-the first and second sound. In two-dimensional systems, thermal fluctuations preclude long-range order8,9; however, superfluidity nevertheless emerges at a non-zero critical temperature through the infinite-order Berezinskii-Kosterlitz-Thouless (BKT) transition10,11, which is associated with a universal jump12 in the superfluid density without any discontinuities in the thermodynamic properties of the fluid. BKT superfluids are also predicted to support two sounds, but so far this has not been observed experimentally. Here we observe first and second sound in a homogeneous two-dimensional atomic Bose gas, and use the two temperature-dependent sound speeds to determine the superfluid density of the gas13-16. Our results agree with the predictions of BKT theory, including the prediction of a universal jump in the superfluid density at the critical temperature.

Universal prethermal dynamics of Bose gases quenched to unitarity.

Understanding strongly correlated phases of matter, such as the quark-gluon plasma and neutron stars, and in particular the dynamics of such systems, for example, following a Hamiltonian quench (a sudden change in some Hamiltonian parameter, such as the strength of interparticle interactions) is a fundamental challenge in modern physics. Ultracold atomic gases are excellent quantum simulators for these problems, owing to their tunable interparticle interactions and experimentally resolvable intrinsic timescales. In particular, they provide access to the unitary regime, in which the interactions are as strong as allowed by quantum mechanics. This regime has been extensively studied in Fermi gases1,2. The less-explored unitary Bose gases3-11 offer possibilities12 such as universal physics controlled solely by the gas density13,14 and new forms of superfluidity15-17. Here, through momentum- and time-resolved studies, we explore degenerate and thermal homogeneous Bose gases quenched to unitarity. In degenerate samples, we observe universal post-quench dynamics in agreement with the emergence of a prethermal state18-24 with a universal non-zero condensed fraction22,24. In thermal gases, the dynamic and thermodynamic properties generally depend on the gas density and the temperature, but we find that they can still be expressed in terms of universal dimensionless functions. Surprisingly, we find that the total quench-induced correlation energy is independent of the gas temperature. These measurements provide quantitative benchmarks and challenges for the theory of unitary Bose gases.

Laughlin's Topological Charge Pump in an Atomic Hall Cylinder.

The quantum Hall effect occurring in two-dimensional electron gases was first explained by Laughlin, who developed a thought experiment that laid the groundwork for our understanding of topological quantum matter. His proposal is based on a quantum Hall cylinder periodically driven by an axial magnetic field, resulting in the quantized motion of electrons. We realize this milestone experiment with an ultracold gas of dysprosium atoms, the cyclic dimension being encoded in the electronic spin and the axial field controlled by the phases of laser-induced spin-orbit couplings. Our experiment provides a straightforward manifestation of the nontrivial topology of quantum Hall insulators, and could be generalized to strongly correlated topological systems.

Many-Body Decay of the Gapped Lowest Excitation of a Bose-Einstein Condensate.

We study the decay mechanism of the gapped lowest-lying axial excitation of a quasipure atomic Bose-Einstein condensate confined in a cylindrical box trap. Owing to the absence of accessible lower-energy modes, or direct coupling to an external bath, this excitation is protected against one-body (linear) decay, and the damping mechanism is exclusively nonlinear. We develop a universal theoretical model that explains this fundamentally nonlinear damping as a process whereby two quanta of the gapped lowest excitation mode couple to a higher-energy mode, which subsequently decays into a continuum. We find quantitative agreement between our experiments and the predictions of this model. Finally, by strongly driving the system below its (lowest) resonant frequency, we observe third-harmonic generation, a hallmark of nonlinear behavior.

Probing Quantum Criticality and Symmetry Breaking at the Microscopic Level.

We report on an experimental study of the Lipkin-Meshkov-Glick model of quantum spins interacting at infinite range in a transverse magnetic field, which exhibits a ferromagnetic phase transition in the thermodynamic limit. We use dysprosium atoms of electronic spin J=8, subjected to a quadratic Zeeman light shift, to simulate 2J=16 interacting spins 1/2. We probe the system microscopically using single magnetic sublevel resolution, giving access to the spin projection parity, which is the collective observable characterizing the underlying Z_{2} symmetry. We measure the thermodynamic properties and dynamical response of the system, and we study the quantum critical behavior around the transition point. In the ferromagnetic phase, we achieve coherent tunneling between symmetry-broken states, and we test the link between symmetry breaking and the appearance of a finite order parameter.

Enhanced Magnetic Sensitivity with Non-Gaussian Quantum Fluctuations.

The precision of a quantum sensor can overcome its classical counterpart when its constituents are entangled. In Gaussian squeezed states, quantum correlations lead to a reduction of the quantum projection noise below the shot noise limit. However, the most sensitive states involve complex non-Gaussian quantum fluctuations, making the required measurement protocol challenging. Here we measure the sensitivity of nonclassical states of the electronic spin J=8 of dysprosium atoms, created using light-induced nonlinear spin coupling. Magnetic sublevel resolution enables us to reach the optimal sensitivity of non-Gaussian (oversqueezed) states, well above the capability of squeezed states and about half the Heisenberg limit.

The essential function of the Trypanosoma brucei Trl1 homolog in procyclic cells is maturation of the intron-containing tRNATyr.

Trypanosoma brucei, the etiologic agent of sleeping sickness, encodes a single intron-containing tRNA, tRNA(Tyr), and splicing is essential for its viability. In Archaea and Eukarya, tRNA splicing requires a series of enzymatic steps that begin with intron cleavage by a tRNA-splicing endonuclease and culminates with joining the resulting tRNA exons by a splicing tRNA ligase. Here we explored the function of TbTrl1, the T. brucei homolog of the yeast Trl1 tRNA ligase. We used a combination of RNA interference and molecular biology approaches to show that down-regulation of TbTrl1 expression leads to accumulation of intron-containing tRNA(Tyr) and a concomitant growth arrest at the G1 phase. These defects were efficiently rescued by expression of an "intronless" version of tRNA(Tyr) in the same RNAi cell line. Taken together, these experiments highlight the crucial importance of the TbTrl1 for tRNA(Tyr) maturation and viability, while revealing tRNA splicing as its only essential function.

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.

Universal Scaling Laws in the Dynamics of a Homogeneous Unitary Bose Gas.

We study the dynamics of an initially degenerate homogeneous Bose gas after an interaction quench to the unitary regime at a magnetic Feshbach resonance. As the cloud decays and heats, it exhibits a crossover from degenerate- to thermal-gas behavior, both of which are characterized by universal scaling laws linking the particle-loss rate to the total atom number N. In the degenerate and thermal regimes, the per-particle loss rate is ∝N^{2/3} and N^{26/9}, respectively. The crossover occurs at a universal kinetic energy per particle and at a universal time after the quench, in units of energy and time set by the gas density. By slowly sweeping the magnetic field away from the resonance and creating a mixture of atoms and molecules, we also map out the dynamics of correlations in the unitary gas, which display a universal temporal scaling with the gas density, and reach a steady state while the gas is still degenerate.

Two-Particle Four-Mode Interferometer for Atoms.

We present a free-space interferometer to observe two-particle interference of a pair of atoms with entangled momenta. The source of atom pairs is a Bose-Einstein condensate subject to a dynamical instability, and the interferometer is realized using Bragg diffraction on optical lattices, in the spirit of our recent Hong-Ou-Mandel experiment. We report on an observation ruling out the possibility of a purely mixed state at the input of the interferometer. We explain how our current setup can be extended to enable a test of a Bell inequality on momentum observables.

Quasiparticle Energy in a Strongly Interacting Homogeneous Bose-Einstein Condensate.

Using two-photon Bragg spectroscopy, we study the energy of particlelike excitations in a strongly interacting homogeneous Bose-Einstein condensate, and observe dramatic deviations from Bogoliubov theory. In particular, at large scattering length a the shift of the excitation resonance from the free-particle energy changes sign from positive to negative. For an excitation with wave number q, this sign change occurs at a≈4/(πq), in agreement with the Feynman energy relation and the static structure factor expressed in terms of the two-body contact. For a≳3/q we also see a breakdown of this theory, and better agreement with calculations based on the Wilson operator product expansion. Neither theory explains our observations across all interaction regimes, inviting further theoretical efforts.

Realization of an atomic quantum Hall system in four dimensions.

Modern condensed matter physics relies on the concept of topology to classify matter, from quantum Hall systems to topological insulators. Engineered systems, benefiting from synthetic dimensions, can potentially give access to topological states predicted in dimensions D > 3. We report the realization of an atomic quantum Hall system evolving in four dimensions (4D), with two spatial dimensions and two synthetic ones encoded in the large spin of dysprosium atoms. We measure the nontrivial topological index of the ground band through a full characterization of the nonlinear electromagnetic response and observe the associated anisotropic hyperedge modes. We also excite nonplanar cyclotron motion, in contrast to the planar orbits in D ≤ 3. Our work may enable the investigation of strongly correlated topological liquids in 4D, generalizing fractional quantum Hall states.

Expanding the Drosophila toolkit for dual control of gene expression.

The ability to independently control gene expression in two different tissues in the same animal is emerging as a major need, especially in the context of inter-organ communication studies. This type of study is made possible by technologies combining the GAL4/UAS and a second binary expression system such as the LexA-system or QF-system. Here, we describe a resource of reagents that facilitate combined use of the GAL4/UAS and a second binary system in various Drosophila tissues. Focusing on genes with well-characterizsed GAL4 expression patterns, we generated a set of more than 40 LexA-GAD and QF2 insertions by CRISPR knock-in and verified their tissue-specificity in larvae. We also built constructs that encode QF2 and LexA-GAD transcription factors in a single vector. Following successful integration of this construct into the fly genome, FLP/FRT recombination is used to isolate fly lines that express only QF2 or LexA-GAD. Finally, using new compatible shRNA vectors, we evaluated both LexA and QF systems for in vivo gene knockdown and are generating a library of such RNAi fly lines as a community resource. Together, these LexA and QF system vectors and fly lines will provide a new set of tools for researchers who need to activate or repress two different genes in an orthogonal manner in the same animal.

Expanding the Drosophila toolkit for dual control of gene expression.

The ability to independently control gene expression in two different tissues in the same animal is emerging as a major need, especially in the context of inter-organ communication studies. This type of study is made possible by technologies combining the GAL4/UAS and a second binary expression system such as the LexA system or QF system. Here, we describe a resource of reagents that facilitate combined use of the GAL4/UAS and a second binary system in various Drosophila tissues. Focusing on genes with well-characterized GAL4 expression patterns, we generated a set of more than 40 LexA-GAD and QF2 insertions by CRISPR knock-in and verified their tissue specificity in larvae. We also built constructs that encode QF2 and LexA-GAD transcription factors in a single vector. Following successful integration of this construct into the fly genome, FLP/FRT recombination is used to isolate fly lines that express only QF2 or LexA-GAD. Finally, using new compatible shRNA vectors, we evaluated both LexA and QF systems for in vivo gene knockdown and are generating a library of such RNAi fly lines as a community resource. Together, these LexA and QF system vectors and fly lines will provide a new set of tools for researchers who need to activate or repress two different genes in an orthogonal manner in the same animal.

In order for researchers to understand how organisms develop and function, they often switch specific genes on or off in certain tissues or at selected times. This can be achieved using genetic tools called binary expression systems. In the fruit fly ­ a popular organism for studying biological processes ­ the most common is the GAL4/UAS system. In this system, a protein called GAL4 is expressed in a specific organ or tissue where it activates a UAS element ­ a genetic sequence that is inserted in front of the gene that is to be switched on. This can also include genes inserted into the fruit fly encoding fluorescent proteins or stretches of DNA coding for factors that can silence specific genes. For example, fruit flies expressing GAL4 protein specifically in nerve cells and a UAS element in front of a gene for a fluorescent protein will display fluorescent nerve cells, which can then be examined using fluorescence microscopy. Studying how organs communicate with one other can require controlled expression of multiple genes at the same time. In fruit flies, other binary expression systems that are analogous to the GAL4/UAS system (known as LexA/LexAop and QF/QUAS) can be used in tandem. For example, to study gut-brain communication, the GAL4/UAS system might be used to switch on the gene for an insulin-like protein in the gut, with one of the other systems controlling the expression of its corresponding receptor in the brain. However, these experiments are currently difficult because, while there are thousands of GAL4/UAS genetic lines, there are only a few LexA/LexAop and QF/QUAS genetic lines. To address this lack of resources, Zirin et al. produced a range of genetically engineered fruit flies containing the LexA/LexAop and QF/QUAS binary expression systems. The flies expressed LexA or QF in each of the major fly organs, including the brain, heart, muscles, and gut. A fluorescent reporter gene linked to the LexAop or QUAS elements, respectively, was then used to test the specificity to single organs and compare the different systems. In some organs the LexA/LexAop system was more reliable than the QF/QUAS system. However, both systems could be successfully combined with genetic elements to switch on a fluorescent reporter gene or switch off a gene of interest in the intended organ. The resources developed by Zirin et al. expand the toolkit for studying fruit fly biology. In future, it will be important to understand the differences between GAL4, LexA and QF systems, and to increase the number of fruit fly lines containing the newer binary expression systems.

Characterization of a multidrug-resistant chronic myeloid leukemia cell line presenting multiple resistance mechanisms.

The multidrug-resistant (MDR) phenotype is multifactorial, and cell lines presenting multiple resistance mechanisms might be good models to understand the importance of the various pathways involved. The present work characterized a MDR chronic myeloid leukemia cell line, derived from K562 through a selective process using daunorubicin. This MDR cell line was shown to be resistant to vincristine, daunorubicin, and partially resistant to imatinib. It showed a slower duplication rate. Overexpression of ABCB1 and ABCC1 was observed at the protein and functional levels and the expression of CD95, a molecule related to cell death, was reduced in the MDR cell line. Conversely, no differences were observed related to the anti-apoptotic molecule Bcl-2 or p53 expression. The activation antigen CD69 was reduced in the MDR cell line and treatment with imatinib further decreased the expressed levels. Furthermore, secretion of IL-8 was diminished in the MDR cell line. When daunorubicin-selected cells were compared to another MDR cell line, Lucena 1, derived from the same parental line K562, and selected with vincristine, a different profile was observed in relation to most aspects studied. When both cell lines were silenced for ABCB1, differences in CD69 and CD95 were maintained, despite resistance reversal. These results reinforce the idea that cell lines selected in vitro may display multiple resistance strategies that may vary with the selective agent used as well as during different steps of the selection process.

Maresin-2 inhibits inflammatory and neuropathic trigeminal pain and reduces neuronal activation in the trigeminal ganglion.

Pain is a common symptom associated with disorders involving the orofacial structures. Most acute orofacial painful conditions are easily recognized, but the pharmacological treatment may be limited by the adverse events of current available drugs and/or patients' characteristics. In addition, chronic orofacial pain conditions represent clinical challenges both, in terms of diagnostic and treatment. There is growing evidence that specialized pro-resolution lipid mediators (SPMs) present potent analgesic effects, in addition to their well characterized role in the resolution of inflammation. Maresins (MaR-1 and MaR-2) were the last described members of this family, and MaR-2 analgesic action has not yet been reported. Herein the effect of MaR-2 in different orofacial pain models was investigated. MaR-2 (1 or 10 ng) was always delivered via medullary subarachnoid injection, which corresponds to the intrathecal treatment. A single injection of MaR-2 caused a significant reduction of phases I and II of the orofacial formalin test in rats. Repeated injections of MaR-2 prevented the development of facial heat and mechanical hyperalgesia in a model of post-operative pain in rats. In a model of trigeminal neuropathic pain (CCI-ION), repeated MaR-2 injections reversed facial heat and mechanical hyperalgesia in rats and mice. CCI-ION increased c-Fos positive neurons and CGRP+ activated (nuclear pNFkB) neurons in the trigeminal ganglion (TG), which were restored to sham levels by MaR-2 repeated treatment. In conclusion, MaR-2 showed potent and long-lasting analgesic effects in inflammatory and neuropathic pain of orofacial origin and the inhibition of CGRP-positive neurons in the TG may account for MaR-2 action.

Multifunctional bilayer membranes composed of poly(lactic acid), beta-chitin whiskers and silver nanoparticles for wound dressing applications.

Nanomaterial-based wound dressings have been extensively studied for the treatment of both minor and life-threatening tissue injuries. These wound dressings must possess several crucial characteristics, such as tissue compatibility, non-toxicity, appropriate biodegradability to facilitate wound healing, effective antibacterial activity to prevent infection, and adequate physical and mechanical strength to withstand repetitive dynamic forces that could potentially disrupt the healing process. Nevertheless, the development of nanostructured wound dressings that incorporate various functional micro- and nanomaterials in distinct architectures, each serving specific purposes, presents significant challenges. In this study, we successfully developed a novel multifunctional wound dressing based on poly(lactic acid) (PLA) fibrous membranes produced by solution-blow spinning (SBS) and electrospinning. The PLA-based membranes underwent surface modifications aimed at tailoring their properties for utilization as effective wound dressing platforms. Initially, beta-chitin whiskers were deposited onto the membrane surface through filtration, imparting hydrophilic character. Afterward, silver nanoparticles (AgNPs) were incorporated onto the beta-chitin layer using a spray deposition method, resulting in platforms with antimicrobial properties against both Staphylococcus aureus and Escherichia coli. Cytotoxicity studies demonstrated the biocompatibility of the membranes with the neonatal human dermal fibroblast (HDFn) cell line. Moreover, bilayer membranes exhibited a high surface area and porosity (> 80%), remarkable stability in aqueous media, and favorable mechanical properties, making them promising candidates for application as multifunctional wound dressings.

Antinociceptive and anxiolytic-like effects of Lavandula angustifolia essential oil on rat models of orofacial pain.

BACKGROUND: Nociceptive and inflammatory orofacial pain is highly prevalent in the population, which justifies the search for safer analgesics. There is increasing evidence of the analgesic and anxiolytic potential of Lavandula angustifolia essential oil (LAV EO), which may represent, when administered through inhalation, may represent a safer alternative for pain treatment. OBJECTIVE: to evaluate whether LAV EO has antinociceptive effect in the formalin test, and anti-hyperalgesic and anxiolytic-like effects in rats subjected to a model of orofacial postoperative pain. METHODOLOGY: Female Wistar rats were exposed to LAV EO (5%) by inhalation for 30 minutes. After exposure, animals were injected with formalin (2.5%, 50 µL) or saline into the hind paw or upper lip and the number of flinches or facial grooming time, respectively, were evaluated. Likewise, on day 3 after intraoral mucosa incision, the animals were exposed to LAV EO and facial mechanical, and heat hyperalgesia were assessed. The influence of LAV EO inhalation on anxiety-like behavior was assessed in operated rats by testing them on the open field (OF) and elevated plus maze (EPM). RESULTS: LAV EO reduced the phase II of the paw formalin test and both phases of the orofacial formalin test. On day three post-incision, LAV EO reduced heat and mechanical hyperalgesia, from 30 minutes up to three hours, and reduced the anxiety-like behavior in operated rats without causing locomotor deficit. CONCLUSION: LAV EO inhalation results in antinociceptive and anxiolytic-like effects in orofacial pain models, which encourages further studies on LAV EO indications and effectiveness on orofacial pain conditions.

Sex Dimorphism in Resolvin D5-induced Analgesia in Rat Models of Trigeminal Pain.

Resolvin D5 (RvD5) is a specialized pro-resolving lipid mediator with potent anti-inflammatory and analgesic properties. Orofacial pain conditions, especially those that are chronic, present clinical challenges in terms of pharmacological management. Thus, new therapeutic options are clearly warranted. Herein, we investigated the antinociceptive effect of RvD5 in the chronic constriction injury of the infraorbital nerve (CCI-ION) model and in the orofacial formalin test in female and male Wistar rats. Our results indicated that repeated subarachnoid medullary injections of RvD5 at 10 ng resulted in a significant reduction of heat and mechanical hyperalgesia induced by the CCI-ION in male and female rats, but males were more sensitive to RvD5 effects. In addition, after CCI-ION, interleukin-6 (IL-6) level was increased in the trigeminal nucleus caudalis of male, but not female rats, which was reduced by RvD5 repeated treatment. No changes in the levels of IL-1ß were found. Minocycline blocked the effect of RvD5 in male rats but failed to affect RvD5 antinociceptive effect in females. Moreover, a single medullary injection of RvD5 caused a significant reduction of formalin-induced facial grooming, in phases I and II of the test, but only in male rats. This study demonstrated for the first time the analgesic effect of RvD5 in trigeminal pain models, and corroborated previous evidence of sex dichotomy, with a greater effect in males. This article presents a translational potential of RvD5 for targeted therapies aiming at the control of acute and chronic trigeminal pain, but further studies are needed to elucidate its sex-related mechanisms. PERSPECTIVE: This study demonstrated that RvD5 may provide the benefits for trigeminal neuropathic pain treatment in male and female rats, but its effect on inflammatory orofacial pain seems to be restricted only to males. Also, it provided the evidence for sex dichotomy in the mechanisms related to the antinociceptive effect of RvD5.