2,804 research outputs found
Heterogeneity in Surface Sensing Suggests a Division of Labor in Pseudomonas aeruginosa Populations
The second messenger signaling molecule cyclic diguanylate monophosphate (c-di-GMP) drives the transition between planktonic and biofilm growth in many bacterial species. Pseudomonas aeruginosa has two surface sensing systems that produce c-di-GMP in response to surface adherence. Current thinking in the field is that once cells attach to a surface, they uniformly respond by producing c-di-GMP. Here, we describe how the Wsp system generates heterogeneity in surface sensing, resulting in two physiologically distinct subpopulations of cells. One subpopulation has elevated c-di-GMP and produces biofilm matrix, serving as the founders of initial microcolonies. The other subpopulation has low c-di-GMP and engages in surface motility, allowing for exploration of the surface. We also show that this heterogeneity strongly correlates to surface behavior for descendent cells. Together, our results suggest that after surface attachment, P. aeruginosa engages in a division of labor that persists across generations, accelerating early biofilm formation and surface exploration
The space group classification of topological band insulators
Topological band insulators (TBIs) are bulk insulating materials which
feature topologically protected metallic states on their boundary. The existing
classification departs from time-reversal symmetry, but the role of the crystal
lattice symmetries in the physics of these topological states remained elusive.
Here we provide the classification of TBIs protected not only by time-reversal,
but also by crystalline symmetries. We find three broad classes of topological
states: (a) Gamma-states robust against general time-reversal invariant
perturbations; (b) Translationally-active states protected from elastic
scattering, but susceptible to topological crystalline disorder; (c) Valley
topological insulators sensitive to the effects of non-topological and
crystalline disorder. These three classes give rise to 18 different
two-dimensional, and, at least 70 three-dimensional TBIs, opening up a route
for the systematic search for new types of TBIs.Comment: Accepted in Nature Physic
Current approaches and future perspectives on strategies for the development of personalized tissue engineering therapies
Personalized tissue engineering and regenerative medicine (TERM) therapies propose patient-oriented effective solutions, considering individual needs. Cell-based therapies, for example, may benefit from cell sources that enable easier autologous set-ups or from recent developments on IPS cells technologies towards effective personalized therapeutics. Furthermore, the customization of scaffold materials to perfectly fit a patientâ s tissue defect through rapid prototyping technologies, also known as 3D printing, is now a reality. Nevertheless, the timing to expand cells or to obtain functional in vitrotissue substitutes prior to implantation prevents advancements towards routine use upon patient´s needs. Thus, personalized therapies also anticipate the importance of creating off-the-shelf solutions to enable immediately available tissue engineered products. This paper reviews the main recent developments and future challenges to enable personalized TERM approaches and to bring these technologies closer to clinical applications.The authors wish to acknowledge the financial support of
the Portuguese Foundation for Science and Technology for
the post-doctoral grant (SFRH/BPD/111729/2015) and
Recognize (UTAP-ICDT/CTM-BIO/0023/2014), and the project
RL3 -TECT -NORTE-07-0124-FEDER-000020 co-financed by
ON.2 (NSRF), through ERDF
A topological Dirac insulator in a quantum spin Hall phase : Experimental observation of first strong topological insulator
When electrons are subject to a large external magnetic field, the
conventional charge quantum Hall effect \cite{Klitzing,Tsui} dictates that an
electronic excitation gap is generated in the sample bulk, but metallic
conduction is permitted at the boundary. Recent theoretical models suggest that
certain bulk insulators with large spin-orbit interactions may also naturally
support conducting topological boundary states in the extreme quantum limit,
which opens up the possibility for studying unusual quantum Hall-like phenomena
in zero external magnetic field. Bulk BiSb single crystals are
expected to be prime candidates for one such unusual Hall phase of matter known
as the topological insulator. The hallmark of a topological insulator is the
existence of metallic surface states that are higher dimensional analogues of
the edge states that characterize a spin Hall insulator. In addition to its
interesting boundary states, the bulk of BiSb is predicted to
exhibit three-dimensional Dirac particles, another topic of heightened current
interest. Here, using incident-photon-energy-modulated (IPEM-ARPES), we report
the first direct observation of massive Dirac particles in the bulk of
BiSb, locate the Kramers' points at the sample's boundary and
provide a comprehensive mapping of the topological Dirac insulator's gapless
surface modes. These findings taken together suggest that the observed surface
state on the boundary of the bulk insulator is a realization of the much sought
exotic "topological metal". They also suggest that this material has potential
application in developing next-generation quantum computing devices.Comment: 16 pages, 3 Figures. Submitted to NATURE on 25th November(2007
AZD8055 enhances in vivo efficacy of afatinib in chordomas
Chordomas are primary bone tumors that arise in the cranial base, mobile spine, and sacrococcygeal region, affecting patients of all ages. Currently, there are no approved agents for chordoma patients. Here, we evaluated the anti-tumor efficacy of small molecule inhibitors that target oncogenic pathways in chordoma, as single agents and in combination, to identify novel therapeutic approaches with the greatest translational potential. A panel of small molecule compounds was screened in vivo against patient-derived xenograft (PDX) models of chordoma, and potentially synergistic combinations were further evaluated using chordoma cell lines and xenograft models. Among the tested agents, inhibitors of EGFR (BIBX 1382, erlotinib, and afatinib), c-MET (crizotinib), and mTOR (AZD8055) significantly inhibited tumor growth in vivo but did not induce tumor regression. Co-inhibition of EGFR and c-MET using erlotinib and crizotinib synergistically reduced cell viability in chordoma cell lines but did not result in enhanced in vivo activity. Co-inhibition of EGFR and mTOR pathways using afatinib and AZD8055 synergistically reduced cell viability in chordoma cell lines. Importantly, this dual inhibition completely suppressed tumor growth in vivo, showing improved tumor control. Together, these data demonstrate that individual inhibitors of EGFR, c-MET, and mTOR pathways suppress chordoma growth both in vitro and in vivo. mTOR inhibition increased the efficacy of EGFR inhibition on chordoma growth in several preclinical models. The insights gained from our study potentially provide a novel combination therapeutic strategy for patients with chordoma. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland
Gate-tuned normal and superconducting transport at the surface of a topological insulator
Three-dimensional topological insulators are characterized by the presence of
a bandgap in their bulk and gapless Dirac fermions at their surfaces. New
physical phenomena originating from the presence of the Dirac fermions are
predicted to occur, and to be experimentally accessible via transport
measurements in suitably designed electronic devices. Here we study transport
through superconducting junctions fabricated on thin Bi2Se3 single crystals,
equipped with a gate electrode. In the presence of perpendicular magnetic field
B, sweeping the gate voltage enables us to observe the filling of the Dirac
fermion Landau levels, whose character evolves continuously from electron- to
hole-like. When B=0, a supercurrent appears, whose magnitude can be gate tuned,
and is minimum at the charge neutrality point determined from the Landau level
filling. Our results demonstrate how gated nano-electronic devices give control
over normal and superconducting transport of Dirac fermions at an individual
surface of a three-dimensional topological insulator.Comment: 28 pages, 5 figure
Tunable Multifunctional Topological Insulators in Ternary Heusler Compounds
Recently the Quantum Spin Hall effect (QSH) was theoretically predicted and
experimentally realized in a quantum wells based on binary semiconductor
HgTe[1-3]. QSH state and topological insulators are the new states of quantum
matter interesting both for fundamental condensed matter physics and material
science[1-11]. Many of Heusler compounds with C1b structure are ternary
semiconductors which are structurally and electronically related to the binary
semiconductors. The diversity of Heusler materials opens wide possibilities for
tuning the band gap and setting the desired band inversion by choosing
compounds with appropriate hybridization strength (by lattice parameter) and
the magnitude of spin-orbit coupling (by the atomic charge). Based on the
first-principle calculations we demonstrate that around fifty Heusler compounds
show the band inversion similar to HgTe. The topological state in these
zero-gap semiconductors can be created by applying strain or by designing an
appropriate quantum well structure, similar to the case of HgTe. Many of these
ternary zero-gap semiconductors (LnAuPb, LnPdBi, LnPtSb and LnPtBi) contain the
rare earth element Ln which can realize additional properties ranging from
superconductivity (e. g. LaPtBi[12]) to magnetism (e. g. GdPtBi[13]) and
heavy-fermion behavior (e. g. YbPtBi[14]). These properties can open new
research directions in realizing the quantized anomalous Hall effect and
topological superconductors.Comment: 20 pages, 5 figure
One-dimensional Topological Edge States of Bismuth Bilayers
The hallmark of a time-reversal symmetry protected topologically insulating
state of matter in two-dimensions (2D) is the existence of chiral edge modes
propagating along the perimeter of the system. To date, evidence for such
electronic modes has come from experiments on semiconducting heterostructures
in the topological phase which showed approximately quantized values of the
overall conductance as well as edge-dominated current flow. However, there have
not been any spectroscopic measurements to demonstrate the one-dimensional (1D)
nature of the edge modes. Among the first systems predicted to be a 2D
topological insulator are bilayers of bismuth (Bi) and there have been recent
experimental indications of possible topological boundary states at their
edges. However, the experiments on such bilayers suffered from irregular
structure of their edges or the coupling of the edge states to substrate's bulk
states. Here we report scanning tunneling microscopy (STM) experiments which
show that a subset of the predicted Bi-bilayers' edge states are decoupled from
states of Bi substrate and provide direct spectroscopic evidence of their 1D
nature. Moreover, by visualizing the quantum interference of edge mode
quasi-particles in confined geometries, we demonstrate their remarkable
coherent propagation along the edge with scattering properties that are
consistent with strong suppression of backscattering as predicted for the
propagating topological edge states.Comment: 15 pages, 5 figures, and supplementary materia
Photonic Analogue of Two-dimensional Topological Insulators and Helical One-Way Edge Transport in Bi-Anisotropic Metamaterials
Recent progress in understanding the topological properties of condensed
matter has led to the discovery of time-reversal invariant topological
insulators. Because of limitations imposed by nature, topologically non-trivial
electronic order seems to be uncommon except in small-band-gap semiconductors
with strong spin-orbit interactions. In this Article we show that artificial
electromagnetic structures, known as metamaterials, provide an attractive
platform for designing photonic analogues of topological insulators. We
demonstrate that a judicious choice of the metamaterial parameters can create
photonic phases that support a pair of helical edge states, and that these edge
states enable one-way photonic transport that is robust against disorder.Comment: 13 pages, 3 figure
Emergence of non-centrosymmetric topological insulating phase in BiTeI under pressure
The spin-orbit interaction affects the electronic structure of solids in
various ways. Topological insulators are one example where the spin-orbit
interaction leads the bulk bands to have a non-trivial topology, observable as
gapless surface or edge states. Another example is the Rashba effect, which
lifts the electron-spin degeneracy as a consequence of spin-orbit interaction
under broken inversion symmetry. It is of particular importance to know how
these two effects, i.e. the non-trivial topology of electronic states and
Rashba spin splitting, interplay with each other. Here we show, through
sophisticated first-principles calculations, that BiTeI, a giant bulk Rashba
semiconductor, turns into a topological insulator under a reasonable pressure.
This material is shown to exhibit several unique features such as, a highly
pressure-tunable giant Rashba spin splitting, an unusual pressure-induced
quantum phase transition, and more importantly the formation of strikingly
different Dirac surface states at opposite sides of the material.Comment: 5 figures are include
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