Fabrication and Characterization of Topological Insulator Bi2_2Se3_3 Nanocrystals

In the recently discovered class of materials known as topological insulators, the presence of strong spin-orbit coupling causes certain topological invariants in the bulk to differ from their values in vacuum. The sudden change of invariants at the interface results in metallic, time reversal invariant surface states whose properties are useful for applications in spintronics and quantum computation. However, a key challenge is to fabricate these materials on the nanoscale appropriate for devices and probing the surface. To this end we have produced 2 nm thick nanocrystals of the topological insulator Bi$_2$Se$_3$ via mechanical exfoliation. For crystals thinner than 10 nm we observe the emergence of an additional mode in the Raman spectrum. The emergent mode intensity together with the other results presented here provide a recipe for production and thickness characterization of Bi$_2$Se$_3$ nanocrystals.Comment: 4 pages, 3 figures (accepted for publication in Applied Physics Letters

Optical evidence of surface state suppression in Bi based topological insulators

A key challenge in condensed matter research is the optimization of topological insulator (TI) compounds for the study and future application of their unique surface states. Truly insulating bulk states would allow the exploitation of predicted surface state properties, such as protection from backscattering, dissipationless spin-polarized currents, and the emergence of novel particles. Towards this end, major progress was recently made with the introduction of highly resistive Bi$_2$Te$_2$Se, in which surface state conductance and quantum oscillations are observed at low temperatures. Nevertheless, an unresolved and pivotal question remains: while room temperature ARPES studies reveal clear evidence of TI surface states, their observation in transport experiments is limited to low temperatures. A better understanding of this surface state suppression at elevated temperatures is of fundamental interest, and crucial for pushing the boundary of device applications towards room-temperature operation. In this work, we simultaneously measure TI bulk and surface states via temperature dependent optical spectroscopy, in conjunction with transport and ARPES measurements. We find evidence of coherent surface state transport at low temperatures, and propose that phonon mediated coupling between bulk and surface states suppresses surface conductance as temperature rises.Comment: 13 pages, 10 figure

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Doping-dependent charge dynamics in CuₓBi₂Se₃

Superconducting CuₓBi₂Se₃ has attracted significant attention as a candidate topological superconductor. Besides inducing superconductivity, the introduction of Cu atoms to this material has also been observed to produce a number of unusual features in DC transport and magnetic susceptibility measurements. To clarify the effect of Cu doping, we have performed a systematic optical spectroscopic study of the electronic structure of CuₓBi₂Se₃ as a function of Cu doping. Our measurements reveal an increase in the conduction band effective mass, while both the free carrier density and lifetime remain relatively constant for Cu content greater than x=0.15. The increased mass naturally explains trends in the superfluid density and residual resistivity as well as hints at the complex nature of Cu doping in Bi₂Se₃

The effects of nutrients, fathead minnows, and submersed macrophytes on the invertebrate community and habitat quality of Delta Marsh

The effect of nutrient addition, macrophyte removal and fathead minnow addition on the invertebrate community and habitat quality of Delta Marsh was assessed using 'in situ' enclosures in the Blind Channel. Factors important in determining the stable state of the marsh were chosen as treatments (nutrient addition, submersed macrophyte removal, and fathead minnow addition). The clear water stable state, characterized by low turbidity, low phytoplankton biomass and abundant submersed macrophytes, is most likely when nutrient loading is low, macrophytes are abundant, and top-down control from planktivorous fish is low. The turbid water state, characterized by high turbidity, high phyloplankton biomass and few submersed macrophytes, is most likely when nutrient loading is high, submersed macrophyte biomass is sparse, and top-down control is high. Inorganic nutrient addition (N and P) was found to cause phytoplankton blooms, and thus turbid conditions when submersed macrophyle biomass was relatively low. However, nutrient addition did not cause phytoplankton blooms or turbid conditions when submersed macrophytes were abundant. Addition of fathead minnows resulted in decreased densities of microinvertebrates, and thus a greater biomass of phytoplankton, due to decreased grazing pressure via the trophic cascade. Submersed macrophytes did not provide a refuge for zooplankton from predation by planktivorous young of the year fathead minnows

Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials

Proteomic analysis of a filaggrin-deficient skin organoid model shows evidence of increased transcriptional-translational activity, keratinocyte-immune crosstalk and disordered axon guidance

Background: Atopic eczema is an itchy inflammatory disorder characterised by skin barrier dysfunction. Loss-of-function mutations in the gene encoding filaggrin ( FLG) are a major risk factor, but the mechanisms by which filaggrin haploinsufficiency leads to atopic inflammation remain incompletely understood. Skin as an organ that can be modelled using primary cells in vitro provides the opportunity for selected genetic effects to be investigated in detail.Methods: Primary human keratinocytes and donor-matched primary fibroblasts from healthy individuals were used to create skin organoid models with and without siRNA-mediated knockdown of FLG. Biological replicate sets of organoids were assessed using histological, functional and biochemical measurements.Results: FLG knockdown leads to subtle changes in histology and ultrastructure including a reduction in thickness of the stratum corneum and smaller, less numerous keratohyalin granules. Immature organoids showed evidence of barrier impairment with FLG knockdown, but the mature organoids showed no difference in transepidermal water loss, water content or dye penetration. There was no difference in epidermal ceramide content. Mass spectrometry proteomic analysis detected &gt;8000 proteins per sample. Gene ontology and pathway analyses identified an increase in transcriptional and translational activity but a reduction in proteins contributing to terminal differentiation, including caspase 14, dermokine, AKT1 and TGF-beta-1. Aspects of innate and adaptive immunity were represented in both the up-regulated and down-regulated protein groups, as was the term 'axon guidance'.Conclusions: This work provides further evidence for keratinocyte-specific mechanisms contributing to immune and neurological, as well as structural, aspects of skin barrier dysfunction. Individuals with filaggrin deficiency may derive benefit from future therapies targeting keratinocyte-immune crosstalk and neurogenic pruritus.</p