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Insulators occur in more than one guise; a recent finding was a class of topological insulators, which host a conducting surface juxtaposed with an insulating bulk. Here, we report the observation of an unusual insulating state with an electrically insulating bulk that simultaneously yields bulk quantum oscillations with characteristics of an unconventional Fermi liquid. We present quantum oscillation measurements of magnetic torque in high-purity single crystals of the Kondo insulator SmB6, which reveal quantum oscillation frequencies characteristic of a large three-dimensional conduction electron Fermi surface similar to the metallic rare earth hexaborides such as PrB6 and LaB6. The quantum oscillation amplitude strongly increases at low temperatures, appearing strikingly at variance with conventional metallic behavior.

TMPRSS4 is a novel type II transmembrane serine protease found at the cell surface that is highly expressed in pancreatic, colon and gastric cancer tissues. However, the biological functions of TMPRSS4 in cancer are unknown. Here we show, using reverse transcription–PCR, that TMPRSS4 is highly elevated in lung cancer tissues compared with normal tissues and is also broadly expressed in a variety of human cancer cell lines. Knockdown of TMPRSS4 by small interfering RNA treatment in lung and colon cancer cell lines was associated with reduction of cell invasion and cell-matrix adhesion as well as modulation of cell proliferation. Conversely, the invasiveness, motility and adhesiveness of SW480 colon carcinoma cells were significantly enhanced by TMPRSS4 overexpression. Furthermore, overexpression of TMPRSS4 induced loss of E-cadherin-mediated cell–cell adhesion, concomitant with the induction of SIP1/ZEB2, an E-cadherin transcriptional repressor, and led to epithelial–mesenchymal transition events, including morphological changes, actin reorganization and upregulation of mesenchymal markers. TMPRSS4-overexpressing cells also displayed markedly increased metastasis to the liver in nude mice upon intrasplenic injection. Taken together, these studies suggest that TMPRSS4 controls the invasive and metastatic potential of human cancer cells by facilitating an epithelial–mesenchymal transition; TMPRSS4 may be a potential therapeutic target for cancer treatment.

Numerous volatile organic compounds (VOCs) exist in Earth's atmosphere, most of which originate from biogenic emissions. Despite VOCs' critical role in tropospheric chemistry, studies for evaluating their atmosphere-ecosystem exchange (emission and deposition) have been limited to a few dominant compounds owing to a lack of appropriate measurement techniques. Using a high—mass resolution proton transfer reaction—time of flight—mass spectrometer and an absolute value eddy-covariance method, we directly measured 186 organic ions with net deposition, and 494 that have bidirectional flux. This observation of active atmosphere-ecosystem exchange of the vast majority of detected VOCs poses a challenge to current emission, air quality, and global climate models, which do not account for this extremely large range of compounds. This observation also provides new insight for understanding the atmospheric VOC budget.

Discovery of two dimensional (2D) magnets, showing intrinsic ferromagnetic (FM) or antiferromagnetic (AFM) orders, has accelerated development of novel 2D spintronics, in which all the key components are made of van der Waals (vdW) materials and their heterostructures. High-performing and energy-efficient spin functionalities have been proposed, often relying on current-driven manipulation and detection of the spin states. In this regard, metallic vdW magnets are expected to have several advantages over the widely-studied insulating counterparts, but have not been much explored due to the lack of suitable materials. Here, we report tunable itinerant ferro- and antiferromagnetism in Co-doped Fe 4 GeTe 2 utilizing the vdW interlayer coupling, extremely sensitive to the material composition. This leads to high T N antiferromagnetism of T N  ~ 226 K in a bulk and ~210 K in 8 nm-thick nanoflakes, together with tunable magnetic anisotropy. The resulting spin configurations and orientations are sensitively controlled by doping, magnetic field, and thickness, which are effectively read out by electrical conduction. These findings manifest strong merits of metallic vdW magnets as an active component of vdW spintronic applications. Metallic van der Waals magnets have considerable technological promise, due to their ability to be strongly coupled with electronic currents and integrated in two dimensional heterostructures. Here, Seo et al. demonstrate highly tunable itinerant antiferromagnetism in a van der Waals magnet.

The epithelial–mesenchymal transition (EMT) is the pivotal mechanism underlying the initiation of cancer invasion and metastasis. Although Mel-18 has been implicated in several biological processes in cancer, its function in the EMT of human cancers has not yet been studied. Here, we demonstrate that Mel-18 negatively regulates the EMT by epigenetically modulating miR-205. We identified miR-205 as a novel target of Mel-18 using a microRNA microarray analysis and found that Mel-18 increased miR-205 transcription by the inhibition of DNA methyltransferase-mediated DNA methylation of the miR-205 promoter, thereby downregulating its target genes, ZEB1 and ZEB2 . Furthermore, the loss of Mel-18 promoted ZEB1- and ZEB2-mediated downregulation of E-cadherin transcription and also enhanced the expression of mesenchymal markers, leading to increased migration and invasion in MCF-7 cells. In MDA-MB-231 cells, Mel-18 overexpression restored E-cadherin expression, resulting in reduced migration and invasion. These effects were reversed by miR-205 overexpression or inhibition. A tumor xenograft with Mel-18 knockdown MCF-7 cells consistently showed increased ZEB1 and ZEB2 expression and decreased E-cadherin expression. Taken together, these results suggest that Mel-18 functions as a tumor suppressor by its novel negative control of the EMT, achieved through regulating the expression of miR-205 and its target genes, ZEB1 and ZEB2 .

The understanding of oxidation in forest atmospheres is being challenged by measurements of unexpectedly large amounts of hydroxyl (OH). A significant number of these OH measurements were made by laser-induced fluorescence in low-pressure detection chambers (called Fluorescence Assay with Gas Expansion (FAGE)) using the Penn State Ground-based Tropospheric Hydrogen Oxides Sensor (GTHOS). We deployed a new chemical removal method to measure OH in parallel with the traditional FAGE method in a California forest. The new method gives on average only 40–60% of the OH from the traditional method and this discrepancy is temperature dependent. Evidence indicates that the new method measures atmospheric OH while the traditional method is affected by internally generated OH, possibly from oxidation of biogenic volatile organic compounds. The improved agreement between OH measured by this new technique and modeled OH suggests that oxidation chemistry in at least one forest atmosphere is better understood than previously thought.

Magnetoelectric skyrmions Skyrmions are stable topological textures with particle-like properties, a mathematical concept originally developed to describe nuclear particles, but which in the past decade has found application at all scales from microscopic to cosmological. Skyrmions have proved particularly useful to describe novel spin configurations in magnets, and last year the presence of skyrmions in the magnetic compounds MnSi and Fe 1− x Co x Si was confirmed in neutron scattering experiments. Now Yu et al . present striking real-space images, using transmission electron microscopy, of a two-dimensional skyrmion lattice for the latter compound, in the form of a hexagonal arrangement of swirling spin structures. The lattice is shown to be stable for a wide range of temperatures and magnetic fields. The authors speculate that the observed nanometre-scale spin topology may lead to interesting new magnetoelectric effects. Skyrmions are stable topological textures with particle-like properties — a mathematical concept that was originally used to describe nuclear particles but has since turned up at all scales. Last year, the presence of skyrmions in the magnetic compounds MnSi and Fe 1−x Co x Si was confirmed with neutron-scattering experiments. Here, real-space images are presented of a two-dimensional skyrmion lattice in a thin film of the latter compound. The observed nanometre-scale spin topology might reveal new magneto-transport effects. Crystal order is not restricted to the periodic atomic array, but can also be found in electronic systems such as the Wigner crystal 1 or in the form of orbital order 2 , stripe order 3 and magnetic order. In the case of magnetic order, spins align parallel to each other in ferromagnets and antiparallel in antiferromagnets. In other, less conventional, cases, spins can sometimes form highly nontrivial structures called spin textures 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 . Among them is the unusual, topologically stable skyrmion spin texture, in which the spins point in all the directions wrapping a sphere 4 , 5 , 6 , 7 . The skyrmion configuration in a magnetic solid is anticipated to produce unconventional spin–electronic phenomena such as the topological Hall effect 24 , 25 , 26 . The crystallization of skyrmions as driven by thermal fluctuations has recently been confirmed in a narrow region of the temperature/magnetic field ( T – B ) phase diagram in neutron scattering studies of the three-dimensional helical magnets MnSi (ref. 17 ) and Fe 1− x Co x Si (ref. 22 ). Here we report real-space imaging of a two-dimensional skyrmion lattice in a thin film of Fe 0.5 Co 0.5 Si using Lorentz transmission electron microscopy. With a magnetic field of 50–70 mT applied normal to the film, we observe skyrmions in the form of a hexagonal arrangement of swirling spin textures, with a lattice spacing of 90 nm. The related T – B phase diagram is found to be in good agreement with Monte Carlo simulations. In this two-dimensional case, the skyrmion crystal seems very stable and appears over a wide range of the phase diagram, including near zero temperature. Such a controlled nanometre-scale spin topology in a thin film may be useful in observing unconventional magneto-transport effects.

In the quest to increase the critical temperature T c of cuprate superconductors, it is essential to identify the factors that limit the strength of superconductivity. The upper critical field H c2 is a fundamental measure of that strength, yet there is no agreement on its magnitude and doping dependence in cuprate superconductors. Here we show that the thermal conductivity can be used to directly detect H c2 in the cuprates YBa 2 Cu 3 O y , YBa 2 Cu 4 O 8 and Tl 2 Ba 2 CuO 6+ δ , allowing us to map out H c2 across the doping phase diagram. It exhibits two peaks, each located at a critical point where the Fermi surface of YBa 2 Cu 3 O y is known to undergo a transformation. Below the higher critical point, the condensation energy, obtained directly from H c2 , suffers a sudden 20-fold collapse. This reveals that phase competition—associated with Fermi-surface reconstruction and charge-density-wave order—is a key limiting factor in the superconductivity of cuprates. The point at which a magnetic field kills superconductivity in the cuprates has been difficult to measure. Grissonnanche et al . use thermal conductivity measurements to reliably determine this field and find that it drops suddenly below some critical doping, suggesting the onset of a new competing phase.

Background Master protocols, classified as basket trials, umbrella trials, and platform trials, are novel designs that investigate multiple hypotheses through concurrent sub-studies (e.g., multiple treatments or populations or that allow adding/removing arms during the trial), offering enhanced efficiency and a more ethical approach to trial evaluation. Despite the many advantages of these designs, they are infrequently used. Methods We conducted a landscape analysis of master protocols using a systematic literature search to determine what trials have been conducted and proposed for an overall goal of improving the literacy in this emerging concept. On July 8, 2019, English-language studies were identified from MEDLINE, EMBASE, and CENTRAL databases and hand searches of published reviews and registries. Results We identified 83 master protocols (49 basket, 18 umbrella, and 16 platform trials). The number of master protocols has increased rapidly over the last five years. Most have been conducted in the US ( n = 44/83) and investigated experimental drugs ( n = 82/83) in the field of oncology ( n = 76/83). The majority of basket trials were exploratory (i.e., phase I/II; n = 47/49) and not randomized ( n = 44/49), and more than half ( n = 28/48) investigated only a single intervention. The median sample size of basket trials was 205 participants (interquartile range, Q3-Q1 [IQR]: 500–90 = 410), and the median study duration was 22.3 (IQR: 74.1–42.9 = 31.1) months. Similar to basket trials, most umbrella trials were exploratory ( n = 16/18), but the use of randomization was more common ( n = 8/18). The median sample size of umbrella trials was 346 participants (IQR: 565–252 = 313), and the median study duration was 60.9 (IQR: 81.3–46.9 = 34.4) months. The median number of interventions investigated in umbrella trials was 5 (IQR: 6–4 = 2). The majority of platform trials were randomized ( n = 15/16), and phase III investigation ( n = 7/15; one did not report information on phase) was more common in platform trials with four of them using seamless II/III design. The median sample size was 892 (IQR: 1835–255 = 1580), and the median study duration was 58.9 (IQR: 101.3–36.9 = 64.4) months. Conclusions We anticipate that the number of master protocols will continue to increase at a rapid pace over the upcoming decades. More efforts to improve awareness and training are needed to apply these innovative trial design methods to fields outside of oncology.

In zebrafish, Müller glia (MG) are a source of retinal stem cells that can replenish damaged retinal neurons and restore vision 1 . In mammals, however, MG do not spontaneously re-enter the cell cycle to generate a population of stem or progenitor cells that differentiate into retinal neurons. Nevertheless, the regenerative machinery may exist in the mammalian retina, as retinal injury can stimulate MG proliferation followed by limited neurogenesis 2 – 7 . Therefore, there is still a fundamental question regarding whether MG-derived regeneration can be exploited to restore vision in mammalian retinas. Gene transfer of β-catenin stimulates MG proliferation in the absence of injury in mouse retinas 8 . Here we report that following gene transfer of β-catenin, cell-cycle-reactivated MG can be reprogrammed to generate rod photoreceptors by subsequent gene transfer of transcription factors essential for rod cell fate specification and determination. MG-derived rods restored visual responses in Gnat1 rd17 Gnat2 cpfl3 double mutant mice, a model of congenital blindness 9 , 10 , throughout the visual pathway from the retina to the primary visual cortex. Together, our results provide evidence of vision restoration after de novo MG-derived genesis of rod photoreceptors in mammalian retinas. Müller glia in mature mouse retina can be stimulated to produce rod cells; this treatment restores visual responses in a model of congenital blindness.