Vortex and half-vortex dynamics in a spinor quantum fluid of interacting polaritons

Spinorial or multi-component Bose-Einstein condensates may sustain fractional quanta of circulation, vorticant topological excitations with half integer windings of phase and polarization. Matter-light quantum fluids, such as microcavity polaritons, represent a unique test bed for realising strongly interacting and out-of-equilibrium condensates. The direct access to the phase of their wavefunction enables us to pursue the quest of whether half vortices ---rather than full integer vortices--- are the fundamental topological excitations of a spinor polariton fluid. Here, we are able to directly generate by resonant pulsed excitations, a polariton fluid carrying either the half or full vortex states as initial condition, and to follow their coherent evolution using ultrafast holography. Surprisingly we observe a rich phenomenology that shows a stable evolution of a phase singularity in a single component as well as in the full vortex state, spiraling, splitting and branching of the initial cores under different regimes and the proliferation of many vortex anti-vortex pairs in self generated circular ripples. This allows us to devise the interplay of nonlinearity and sample disorder in shaping the fluid and driving the phase singularities dynamicsComment: New version complete with revised modelization, discussion and added material. 8 pages, 7 figures. Supplementary videos: https://drive.google.com/folderview?id=0B0QCllnLqdyBfmc2ai0yVF9fa2g2VnZodGUwemVkLThBb3BoOVRKRDJMS2dUdjlZdkRTQk

Twist of generalized skyrmions and spin vortices in a polariton superfluid

We study the spin vortices and skyrmions coherently imprinted into an exciton-polariton condensate on a planar semiconductor microcavity. We demonstrate that the presence of a polarization anisotropy can induce a complex dynamics of these structured topologies, leading to the twist of their circuitation on the Poincare sphere of polarizations. The theoretical description of the results carries the concept of generalized quantum vortices in two-component superfluids, which are conformal with polarization loops around an arbitrary axis in the pseudospin space

Directional Goldstone waves in polariton condensates close to equilibrium

Quantum fluids of light are realized in semiconductor microcavities using exciton-polaritons, solid-state quasi-particles with a light mass and sizeable interactions. Here, we use the microscopic analogue of oceanographic techniques to measure the excitation spectrum of a thermalised polariton condensate. Increasing the fluid density, we demonstrate the transition from a free-particle parabolic dispersion to a linear, sound-like Goldstone mode characteristic of superfluids at equilibrium. Notably, we reveal the effect of an asymmetric pumping by showing that collective excitations are created with a definite direction with respect to the condensate. Furthermore, we measure the critical sound speed for polariton superfluids close to equilibrium

Pulse, polarization and topology shaping of polariton fluids

Here we present different approaches to ultrafast pulse and polarization shaping, based on a “quantum fluid” platform of polaritons. Indeed we exploit the normal modes of two dimensional polariton fluids made of strong coupled quantum well excitons and microcavity photons, by rooting different polarization and topological states into their sub-picosecond Rabi oscillations. Coherent control of two resonant excitation pulses allows us to prepare the desired state of the polariton, taking benefit from its four-component features given by the combination of the two normal modes with the two degrees of polarization. An ultrafast imaging based on the digital off-axis holography technique is implemented to study the polariton complex wavefunction with time and space resolution. We show in order coherent control of the polariton state on the Bloch sphere, an ultrafast polarization sweeping of the Poincaré sphere, and the dynamical twist of full Poincaré states such as the skyrmion on the sphere itself. Finally, we realize a new kind of ultrafast swirling vortices by adding the angular momentum degree of freedom to the two-pulse scheme. These oscillating topology states are characterized by one or more inner phase singularities tubes which spirals around the axis of propagation. The mechanism is devised in the splitting of the vortex into the upper and lower polaritons, resulting in an oscillatory exchange of energy and angular momentum and in the emitted time and space structured photonic packets

Topological order and thermal equilibrium in polariton condensates

The Berezinskii–Kosterlitz–Thouless phase transition from a disordered to a quasi-ordered state, mediated by the proliferation of topological defects in two dimensions, governs seemingly remote physical systems ranging from liquid helium, ultracold atoms and superconducting thin films to ensembles of spins. Here we observe such a transition in a short-lived gas of exciton-polaritons, bosonic light–matter particles in semiconductor microcavities. The observed quasi-ordered phase, characteristic for an equilibrium two-dimensional bosonic gas, with a decay of coherence in both spatial and temporal domains with the same algebraic exponent, is reproduced with numerical solutions of stochastic dynamics, proving that the mechanism of pairing of the topological defects (vortices) is responsible for the transition to the algebraic order. This is made possible thanks to long polariton lifetimes in high-quality samples and in a reservoir-free region. Our results show that the joint measurement of coherence both in space and time is required to characterize driven–dissipative phase transitions and enable the investigation of topological ordering in open systems

Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series

The largest kindred with inherited prion disease P102L, historically Gerstmann-Sträussler-Scheinker syndrome, originates from central England, with émigrés now resident in various parts of the English-speaking world. We have collected data from 84 patients in the large UK kindred and numerous small unrelated pedigrees to investigate phenotypic heterogeneity and modifying factors. This collection represents by far the largest series of P102L patients so far reported. Microsatellite and genealogical analyses of eight separate European kindreds support multiple distinct mutational events at a cytosine-phosphate diester-guanidine dinucleotide mutation hot spot. All of the smaller P102L kindreds were linked to polymorphic human prion protein gene codon 129M and were not connected by genealogy or microsatellite haplotype background to the large kindred or each other. While many present with classical Gerstmann-Sträussler-Scheinker syndrome, a slowly progressive cerebellar ataxia with later onset cognitive impairment, there is remarkable heterogeneity. A subset of patients present with prominent cognitive and psychiatric features and some have met diagnostic criteria for sporadic Creutzfeldt-Jakob disease. We show that polymorphic human prion protein gene codon 129 modifies age at onset: the earliest eight clinical onsets were all MM homozygotes and overall age at onset was 7 years earlier for MM compared with MV heterozygotes (P = 0.02). Unexpectedly, apolipoprotein E4 carriers have a delayed age of onset by 10 years (P = 0.02). We found a preponderance of female patients compared with males (54 females versus 30 males, P = 0.01), which probably relates to ascertainment bias. However, these modifiers had no impact on a semi-quantitative pathological phenotype in 10 autopsied patients. These data allow an appreciation of the range of clinical phenotype, modern imaging and molecular investigation and should inform genetic counselling of at-risk individuals, with the identification of two genetic modifiers

Topological order and thermal equilibrium in polariton condensates

We report the observation of the Berezinskii-Kosterlitz-Thouless transition for a 2D gas of exciton-polaritons, and through the joint measurement of the first-order coherence both in space and time we bring compelling evidence of a thermodynamic equilibrium phase transition in an otherwise open driven/dissipative system. This is made possible thanks to long polariton lifetimes in high-quality samples with small disorder and in a reservoir-free region far away from the excitation spot, that allow topological ordering to prevail. The observed quasi-ordered phase, characteristic for an equilibrium 2D bosonic gas, with a decay of coherence in both spatial and temporal domains with the same algebraic exponent, is reproduced with numerical solutions of stochastic dynamics, proving that the mechanism of pairing of the topological defects (vortices) is responsible for the transition to the algebraic order. Finally, measurements in the weak-coupling regime confirm that polariton condensates are fundamentally different from photon lasers and constitute genuine quantum degenerate macroscopic states

Structure-Based Screen Identifies a Potent Small Molecule Inhibitor of Stat5a/b with Therapeutic Potential for Prostate Cancer and Chronic Myeloid Leukemia.

Bypassing tyrosine kinases responsible for Stat5a/b phosphorylation would be advantageous for therapy development for Stat5a/b-regulated cancers. Here, we sought to identify small molecule inhibitors of Stat5a/b for lead optimization and therapy development for prostate cancer and Bcr-Abl-driven leukemias. In silico screening of chemical structure databases combined with medicinal chemistry was used for identification of a panel of small molecule inhibitors to block SH2 domain-mediated docking of Stat5a/b to the receptor-kinase complex and subsequent phosphorylation and dimerization. We tested the efficacy of the lead compound IST5-002 in experimental models and patient samples of two known Stat5a/b-driven cancers, prostate cancer and chronic myeloid leukemia (CML). The lead compound inhibitor of Stat5-002 (IST5-002) prevented both Jak2 and Bcr-Abl-mediated phosphorylation and dimerization of Stat5a/b, and selectively inhibited transcriptional activity of Stat5a (IC50 = 1.5μmol/L) and Stat5b (IC50 = 3.5 μmol/L). IST5-002 suppressed nuclear translocation of Stat5a/b, binding to DNA and Stat5a/b target gene expression. IST5-002 induced extensive apoptosis of prostate cancer cells, impaired growth of prostate cancer xenograft tumors, and induced cell death in patient-derived prostate cancers when tested ex vivo in explant organ cultures. Importantly, IST5-002 induced robust apoptotic death not only of imatinib-sensitive but also of imatinib-resistant CML cell lines and primary CML cells from patients. IST5-002 provides a lead structure for further chemical modifications for clinical development for Stat5a/b-driven solid tumors and hematologic malignancies

Unusual multisystemic involvement and a novel BAG3 mutation revealed by NGS screening in a large cohort of myofibrillar myopathies

Background: Myofibrillar myopathies (MFM) are a group of phenotypically and genetically heterogeneous neuromuscular disorders, which are characterized by protein aggregations in muscle fibres and can be associated with multisystemic involvement. Methods: We screened a large cohort of 38 index patients with MFM for mutations in the nine thus far known causative genes using Sanger and next generation sequencing (NGS). We studied the clinical and histopathological characteristics in 38 index patients and five additional relatives (n = 43) and particularly focused on the associated multisystemic symptoms. Results: We identified 14 heterozygous mutations (diagnostic yield of 37%), among them the novel p.Pro209Gln mutation in the BAG3 gene, which was associated with onset in adulthood, a mild phenotype and an axonal sensorimotor polyneuropathy, in the absence of giant axons at the nerve biopsy. We revealed several novel clinical phenotypes and unusual multisystemic presentations with previously described mutations: hearing impairment with a FLNC mutation, dysphonia with a mutation in DES and the first patient with a FLNC mutation presenting respiratory insufficiency as the initial symptom. Moreover, we described for the first time respiratory insufficiency occurring in a patient with the p.Gly154Ser mutation in CRYAB. Interestingly, we detected a polyneuropathy in 28% of the MFM patients, including a BAG3 and a MYOT case, and hearing impairment in 13%, including one patient with a FLNC mutation and two with mutations in the DES gene. In four index patients with a mutation in one of the MFM genes, typical histological findings were only identified at the ultrastructural level (29%). Conclusions: We conclude that extraskeletal symptoms frequently occur in MFM, particularly cardiac and respiratory involvement, polyneuropathy and/or deafness. BAG3 mutations should be considered even in cases with a mild phenotype or an adult onset. We identified a genetic defect in one of the known genes in less than half of the MFM patients, indicating that more causative genes are still to be found. Next generation sequencing techniques should be helpful in achieving this aim