Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination.

The leucine zipper-like transcriptional regulator 1 (LZTR1) protein, an adaptor for cullin 3 (CUL3) ubiquitin ligase complex, is implicated in human disease, yet its mechanism of action remains unknown. We found that Lztr1 haploinsufficiency in mice recapitulates Noonan syndrome phenotypes, whereas LZTR1 loss in Schwann cells drives dedifferentiation and proliferation. By trapping LZTR1 complexes from intact mammalian cells, we identified the guanosine triphosphatase RAS as a substrate for the LZTR1-CUL3 complex. Ubiquitome analysis showed that loss of Lztr1 abrogated Ras ubiquitination at lysine-170. LZTR1-mediated ubiquitination inhibited RAS signaling by attenuating its association with the membrane. Disease-associated LZTR1 mutations disrupted either LZTR1-CUL3 complex formation or its interaction with RAS proteins. RAS regulation by LZTR1-mediated ubiquitination provides an explanation for the role of LZTR1 in human disease.

Two step reconstruction of traumatic ear skin avulsion using Integra graft.

Treatment of traumatic ear injuries have always been a challenge. Preservation of the auricular cartilage is key for reconstruction. Many techniques have been reported for the management of exposed ear perichondrium. We present patient who sustained right ear soft tissue avulsion. Initial examination the patient revealed skin avulsion with exposed cartilage from the concha, scapha and antihelix on the right ear. The treatment sequence included debridement and application of Integra graft. This was followed by dressing changes every three days and three weeks. Once adequate vascularization was noted a split thickness skin graft was used for final reconstruction. Integra has been widely used for the management of burns as well as exposed bone and cartilage. However, its use in traumatic ear injuries has not been reported. This technique allowed for the reconstruction of a large skin avulsion from the right ear with minimal donor site morbidity and avoidance of local rotational flaps that could hinder later reconstructions if needed.

Robust Type-II Weyl Semimetal Phase in Transition Metal Diphosphides XP_{2} (X=Mo, W).

The recently discovered type-II Weyl points appear at the boundary between electron and hole pockets. Type-II Weyl semimetals that host such points are predicted to exhibit a new type of chiral anomaly and possess thermodynamic properties very different from their type-I counterparts. In this Letter, we describe the prediction of a type-II Weyl semimetal phase in the transition metal diphosphides MoP_{2} and WP_{2}. These materials are characterized by relatively simple band structures with four pairs of type-II Weyl points. Neighboring Weyl points have the same chirality, which makes the predicted topological phase robust with respect to small perturbations of the crystalline lattice. In addition, this peculiar arrangement of the Weyl points results in long topological Fermi arcs, thus making them readily accessible in angle-resolved photoemission spectroscopy.

Nonlocal quantum fluctuations and fermionic superfluidity in the imbalanced attractive Hubbard model.

We study fermionic superfluidity in strongly anisotropic optical lattices with attractive interactions utilizing the cluster dynamical mean-field theory method, and focusing in particular on the role of nonlocal quantum fluctuations. We show that nonlocal quantum fluctuations impact the BCS superfluid transition dramatically. Moreover, we show that exotic superfluid states with a delicate order parameter structure, such as the Fulde-Ferrell-Larkin-Ovchinnikov phase driven by spin population imbalance, can emerge even in the presence of such strong fluctuations.

Critical temperature of interacting Bose gases in periodic potentials.

The superfluid transition of a repulsive Bose gas in the presence of a sinusoidal potential which represents a simple-cubic optical lattice is investigated using quantum Monte Carlo simulations. At the average filling of one particle per well the critical temperature has a nonmonotonic dependence on the interaction strength, with an initial sharp increase and a rapid suppression at strong interactions in the vicinity of the Mott transition. In an optical lattice the positive shift of the transition is strongly enhanced compared to the homogenous gas. By varying the lattice filling we find a crossover from a regime where the optical lattice has the dominant effect to a regime where interactions dominate and the presence of the lattice potential becomes almost irrelevant.

Ferromagnetism of a repulsive atomic Fermi gas in an optical lattice: a quantum Monte Carlo study.

Using continuous-space quantum Monte Carlo methods, we investigate the zero-temperature ferromagnetic behavior of a two-component repulsive Fermi gas under the influence of periodic potentials that describe the effect of a simple-cubic optical lattice. Simulations are performed with balanced and with imbalanced components, including the case of a single impurity immersed in a polarized Fermi sea (repulsive polaron). For an intermediate density below half filling, we locate the transitions between the paramagnetic, and the partially and fully ferromagnetic phases. As the intensity of the optical lattice increases, the ferromagnetic instability takes place at weaker interactions, indicating a possible route to observe ferromagnetism in experiments performed with ultracold atoms. We compare our findings with previous predictions based on the standard computational method used in material science, namely density functional theory, and with results based on tight-binding models.

Preladenant, a selective adenosine A2A receptor antagonist, is not associated with QT/QTc prolongation.

PURPOSE: Preladenant is an orally administered adenosine2A (A2A) receptor antagonist in phase III development for Parkinson's disease treatment. This thorough QT/QTc study evaluated its potential effects on cardiac repolarization. METHODS: This was a randomized, double-blind, positive- and placebo-controlled, four-period crossover study performed under steady-state exposure of clinical and supratherapeutic doses of preladenant (10 mg BID and 100 mg BID, respectively, for 5 days), moxifloxacin (400 mg on day 5), or placebo in 60 healthy adult volunteers. The potential effect on QTcF was measured by the largest upper bound of 95 % one-sided CIs for the mean changes from time-matched baseline ECG recordings compared with placebo. Plasma preladenant concentrations were also determined on day 5. RESULTS: The QTcF difference for moxifloxacin compared with placebo exceeded 5 ms from 1 to 12 h postdose, establishing assay sensitivity. The QTcF interval was similar between the preladenant and placebo treatment groups: the upper bound of the 95 % one-sided CI for the mean difference in QTcF between preladenant and placebo was less than 10 ms at all time points for the supratherapeutic treatment group (1.3 to 5.7 ms, mean difference: -1.3 to 2.7 ms) and the therapeutic treatment group (0.4 to 4.3 ms, mean difference: -2.1 to 1.5 ms), substantially below the threshold of regulatory concern. The supratherapeutic dose (100 mg BID) provided a Cmax margin of 6.1-fold and AUC margin of 6.9-fold, respectively, compared with 10 mg BID. CONCLUSIONS: At clinical and supratherapeutic doses, preladenant is not associated with QTc prolongation.

Bosonic superfluid-insulator transition in continuous space.

We investigate the zero-temperature phase diagram of interacting Bose gases in the presence of a simple cubic optical lattice, going beyond the regime where the mapping to the single-band Bose-Hubbard model is reliable. Our computational approach is a new hybrid quantum Monte Carlo method which combines algorithms used to simulate homogeneous quantum fluids in continuous space with those used for discrete lattice models of strongly correlated systems. We determine the critical interaction strength and optical lattice intensity where the superfluid-to-insulator transition takes place, considering also the regime of shallow optical lattices and strong interatomic interactions. The implications of our findings for the supersolid state of matter are discussed.

Itinerant ferromagnetism of a repulsive atomic Fermi gas: a quantum monte carlo study.

We investigate the phase diagram of a two-component repulsive Fermi gas at T=0 by means of quantum Monte Carlo simulations. Both purely repulsive and resonant attractive model potentials are considered in order to analyze the limits of the universal regime where the details of interatomic forces can be neglected. The equation of state of both balanced and unbalanced systems is calculated as a function of the interaction strength and the critical density for the onset of ferromagnetism is determined. The energy of the strongly polarized gas is calculated and parametrized in terms of the physical properties of repulsive polarons, which are relevant for the stability of the fully ferromagnetic state. Finally, we analyze the phase diagram in the interaction-polarization plane under the assumption that only phases with homogeneous magnetization can be produced.

Quantitative determination of temperature in the approach to magnetic order of ultracold fermions in an optical lattice.

We perform a quantitative simulation of the repulsive Fermi-Hubbard model using an ultracold gas trapped in an optical lattice. The entropy of the system is determined by comparing accurate measurements of the equilibrium double occupancy with theoretical calculations over a wide range of parameters. We demonstrate the applicability of both high-temperature series and dynamical mean-field theory to obtain quantitative agreement with the experimental data. The reliability of the entropy determination is confirmed by a comprehensive analysis of all systematic errors. In the center of the Mott insulating cloud we obtain an entropy per atom as low as 0.77k(B) which is about twice as large as the entropy at the Néel transition. The corresponding temperature depends on the atom number and for small fillings reaches values on the order of the tunneling energy.

Supersolid phase with cold polar molecules on a triangular lattice.

We study a system of heteronuclear molecules on a triangular lattice and analyze the potential of this system for the experimental realization of a supersolid phase. The ground state phase diagram contains superfluid, solid, and supersolid phases. At finite temperatures and strong interactions there is an additional emulsion region, in contrast with similar models with short-range interactions. We derive the maximal critical temperature T{c} and the corresponding entropy S/N=0.04(1) for supersolidity and find feasible experimental conditions for its realization.

Absence of a direct superfluid to mott insulator transition in disordered bose systems.

We prove the absence of a direct quantum phase transition between a superfluid and a Mott insulator in a bosonic system with generic, bounded disorder. We also prove the compressibility of the system on the superfluid-insulator critical line and in its neighborhood. These conclusions follow from a general theorem of inclusions, which states that for any transition in a disordered system, one can always find rare regions of the competing phase on either side of the transition line. Quantum Monte Carlo simulations for the disordered Bose-Hubbard model show an even stronger result, important for the nature of the Mott insulator to Bose glass phase transition: the critical disorder bound Delta(c) corresponding to the onset of disorder-induced superfluidity, satisfies the relation Delta(c)>Eg/2, with Eg/2 the half-width of the Mott gap in the pure system.

Discerning incompressible and compressible phases of cold atoms in optical lattices.

Experiments with cold atoms trapped in optical lattices offer the potential to realize a variety of novel phases but suffer from severe spatial inhomogeneity that can obscure signatures of new phases of matter and phase boundaries. We use a high temperature series expansion to show that compressibility in the core of a trapped Fermi-Hubbard system is related to measurements of changes in double occupancy. This core compressibility filters out edge effects, offering a direct probe of compressibility independent of inhomogeneity. A comparison with experiments is made.

Binding of a 3He impurity to a screw dislocation in solid 4He.

Using first-principles simulations for the probability density of finding a 3He atom in the vicinity of the screw dislocation in solid 4He, we determine the binding energy to the dislocation nucleus E(B)=0.8+/-0.1 K and the density of localized states at larger distances. The specific heat due to 3He features a peak similar to the one observed in recent experiments, and our model can also account for the observed increase in shear modulus at low temperature. We further discuss the role of 3He in the picture of superfluid defects.

Expansion of a quantum gas released from an optical lattice.

We analyze the interference pattern produced by ultracold atoms released from an optical lattice, commonly interpreted as the momentum distributions of the trapped quantum gas. We show that for finite times of flight the resulting density distribution can, however, be significantly altered, similar to a near-field diffraction regime in optics. We illustrate our findings with a simple model and realistic quantum Monte Carlo simulations for bosonic atoms and compare the latter to experiments.

Local stress and superfluid properties of solid 4He.

We provide a semiquantitative tool, derived from first-principles simulations, for answering the question of whether certain types of defects in solid 4He support mass superflow. Although ideal crystals of 4He are not supersolid, the gap for vacancy creation closes when applying a moderate stress. While a homogeneous system becomes unstable at this point, the stressed core of crystalline defects (dislocations and grain boundaries) can turn superfluid.

Deconfined criticality: generic first-order transition in the SU(2) symmetry case.

Monte Carlo simulations of the SU(2)-symmetric deconfined critical point action reveal strong violations of scale invariance for the deconfinement transition. We find compelling evidence that the generic runaway renormalization flow of the gauge coupling is to a weak first-order transition, similar to the case of U(1) x U(1) symmetry. Our results imply that recent numeric studies of the Nèel antiferromagnet to valence bond solid quantum phase transition in SU(2)-symmetric models were not accurate enough in determining the nature of the transition.

Luttinger liquid in the core of a screw dislocation in helium-4.

On the basis of first-principles Monte Carlo simulations we find that the screw dislocation along the hexagonal axis of an hcp 4He crystal features a superfluid (at T-->0) core. This is the first example of a regular quasi-one-dimensional supersolid--the phase featuring both translational and superfluid orders, and one of the cleanest cases of a Luttinger-liquid system. In contrast, the same type of screw dislocation in solid H2 is insulating.

Superfluidity of grain boundaries in solid 4He.

By large-scale quantum Monte Carlo simulations we show that grain boundaries in 4He crystals are generically superfluid at low temperature, with a transition temperature of the order of approximately 0.5 K at the melting pressure; nonsuperfluid grain boundaries are found only for special orientations of the grains. We also find that close vicinity to the melting line is not a necessary condition for superfluid grain boundaries, and a grain boundary in direct contact with the superfluid liquid at the melting curve is found to be mechanically stable and the grain-boundary superfluidity observed by Sasaki et al. [Science 313, 1098 (2006)10.1126/science.1130879] is not just a crack filled with superfluid.