Mn incorporation in as-grown and annealed (Ga,Mn)As layers studied by x-ray diffraction and standing-wave uorescence

A combination of high-resolution x-ray diffraction and a new technique of x-ray standing wave uorescence at grazing incidence is employed to study the structure of (Ga,Mn)As diluted magnetic semiconductor and its changes during post-growth annealing steps. We find that the film is formed by a uniform, single crystallographic phase epilayer covered by a thin surface layer with enhanced Mn concentration due to Mn atoms at random non-crystallographic positions. In the epilayer, Mn incorporated at interstitial position has a dominant effect on lattice expansion as compared to substitutional Mn. The expansion coeffcient of interstitial Mn estimated from our data is consistent with theory predictions. The concentration of interstitial Mn and the corresponding lattice expansion of the epilayer are reduced by annealing, accompanied by an increase of the density of randomly distributed Mn atoms in the disordered surface layer. Substitutional Mn atoms remain stable during the low-temperature annealing.Comment: 9 pages, 9 figure

Ectopic expression of HNF4α in Het1A cells induces an invasive phenotype

\ua9 2023 The AuthorsBarrett\u27s oesophagus (BO) is a pathological condition in which the squamous epithelium of the distal oesophagus is replaced by an intestinal-like columnar epithelium originating from the gastric cardia. Several somatic mutations contribute to the intestinal-like metaplasia. Once these have occurred in a single cell, it will be unable to expand further unless the altered cell can colonise the surrounding squamous epithelium of the oesophagus. The mechanisms by which this happens are still unknown. Here we have established an in vitro system for examining the competitive behaviour of two epithelia. We find that when an oesophageal epithelium model (Het1A cells) is confronted by an intestinal epithelium model (Caco-2 cells), the intestinal cells expand into the oesophageal domain. In this case the boundary involves overgrowth by the Caco-2 cells and the formation of isolated colonies. Two key transcription factors, normally involved in intestinal development, HNF4α and CDX2, are both expressed in BO. We examined the competitive ability of Het1A cells stably expressing HNF4α or CDX2 and placed in confrontation with unmodified Het1A cells. The key result is that stable expression of HNF4α, but not CDX2, increased the ability of the cells to migrate and push into the unmodified Het1A domain. In this situation the boundary between the cell types is a sharp one, as is normally seen in BO. The experiments were conducted using a variety of extracellular substrates, which all tended to increase the cell migration compared to uncoated plastic. These data provide evidence that HNF4α expression could have a potential role in the competitive spread of BO into the oesophagus as HNF4α increases the ability of cells to invade into the adjacent stratified squamous epithelium, thus enabling a single mutant cell eventually to generate a macroscopic patch of metaplasia

Conductive Polymer-Coated 3D Printed Microneedles: Biocompatible Platforms for Minimally Invasive Biosensing Interfaces

\ua9 2023 The Authors. Small published by Wiley-VCH GmbH.Conductive polymeric microneedle (MN) arrays as biointerface materials show promise for the minimally invasive monitoring of analytes in biodevices and wearables. There is increasing interest in microneedles as electrodes for biosensing, but efforts have been limited to metallic substrates, which lack biological stability and are associated with high manufacturing costs and laborious fabrication methods, which create translational barriers. In this work, additive manufacturing, which provides the user with design flexibility and upscale manufacturing, is employed to fabricate acrylic-based microneedle devices. These microneedle devices are used as platforms to produce intrinsically-conductive, polymer-based surfaces based on polypyrrole (PPy) and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS). These entirely polymer-based solid microneedle arrays act as dry conductive electrodes while omitting the requirement of a metallic seed layer. Two distinct coating methods of 3D-printed solid microneedles, in situ polymerization and drop casting, enable conductive functionality. The microneedle arrays penetrate ex vivo porcine skin grafts without compromising conductivity or microneedle morphology and demonstrate coating durability over multiple penetration cycles. The non-cytotoxic nature of the conductive microneedles is evaluated using human fibroblast cells. The proposed fabrication strategy offers a compelling approach to manufacturing polymer-based conductive microneedle surfaces that can be further exploited as platforms for biosensing

Lithographically and electrically controlled strain effects on anisotropic magnetoresistance in (Ga,Mn)As

It has been demonstrated that magnetocrystalline anisotropies in (Ga,Mn)As are sensitive to lattice strains as small as 10^-4 and that strain can be controlled by lattice parameter engineering during growth, through post growth lithography, and electrically by bonding the (Ga,Mn)As sample to a piezoelectric transducer. In this work we show that analogous effects are observed in crystalline components of the anisotropic magnetoresistance (AMR). Lithographically or electrically induced strain variations can produce crystalline AMR components which are larger than the crystalline AMR and a significant fraction of the total AMR of the unprocessed (Ga,Mn)As material. In these experiments we also observe new higher order terms in the phenomenological AMR expressions and find that strain variation effects can play important role in the micromagnetic and magnetotransport characteristics of (Ga,Mn)As lateral nanoconstrictions.Comment: 11 pages, 4 figures, references fixe

3D-Printed Hollow Microneedle-Lateral Flow Devices for Rapid Blood-Free Detection of C-Reactive Protein and Procalcitonin

\ua9 2023 The Authors. Advanced Materials Technologies published by Wiley-VCH GmbH.Hollow microneedle devices as a technology for interstitial fluid extraction show promise for the minimally invasive point-of-care detection of analytes. Despite increasing efforts toward on-patch diagnostics, the use of hollow microneedles has been limited due to the complexity caused by integrating hollow microneedles with established point-of-care diagnostic techniques. Herein, a 3D printing method is utilized, to provide low-cost manufacturing of custom-designed hollow microneedle devices, allowing for easy integration with lateral flow assays for rapid and blood-free diagnostics. Microneedle surface modification through PEGylation results in prolonged and enhanced hydrophilicity, enabling passive uptake of small volume samples (≈22.5 \ub5L) and an enhanced shelf life. The hollow microneedle devices are deemed non-cytotoxic to cell types found within the skin following short-term and prolonged exposure in accordance with ISO10993. Furthermore, the devices demonstrate high mechanical strength and successfully penetrate porcine skin grafts without damaging the surrounding skin morphology. This work also demonstrates for the first time the use of hollow microneedles for the simultaneous detection, at clinically relevant concentrations, of C-reactive protein (LoD = 10 \ub5g mL−1) and procalcitonin (LoD = 1 ng mL−1), through porcine skin, ultimately demonstrating the beneficial use of manufactured 3D-printed hollow microneedles towards low-cost blood-free diagnostics of inflammation markers

Targeting the Hippo/YAP/TAZ signalling pathway: Novel opportunities for therapeutic interventions into skin cancers

\ua9 2022 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.Skin cancers are by far the most frequently diagnosed human cancers. The closely related transcriptional co-regulator proteins YAP and TAZ (WWTR1) have emerged as important drivers of tumour initiation, progression and metastasis in melanoma and non-melanoma skin cancers. YAP/TAZ serve as an essential signalling hub by integrating signals from multiple upstream pathways. In this review, we summarize the roles of YAP/TAZ in skin physiology and tumorigenesis and discuss recent efforts of therapeutic interventions that target YAP/TAZ in in both preclinical and clinical settings, as well as their prospects for use as skin cancer treatments

Cancer-Associated Fibroblasts Suppress CD8⁺ T-cell Infiltration and Confer Resistance to Immune-Checkpoint Blockade

\ua92022 The Authors. Immune-checkpoint blockade (ICB) promotes antitumor immune responses and can result in durable patient benefit. However, response rates in breast cancer patients remain modest, stimulating efforts to discover novel treatment options. Cancer-associated fibroblasts (CAF) represent a major component of the breast tumor microenvironment and have known immunosuppressive functions in addition to their well-established roles in directly promoting tumor growth and metastasis. Here we utilized paired syngeneic mouse mammary carcinoma models to show that CAF abundance is associated with insensitivity to combination aCTLA4 and aPD-L1 ICB. CAF-rich tumors exhibited an immunologically cold tumor microenvironment, with transcriptomic, flow cytometric, and quantitative histopathologic analyses demonstrating a relationship between CAF density and a CD8+ T-cell–excluded tumor phenotype. The CAF receptor Endo180 (Mrc2) is predominantly expressed on myofibroblastic CAFs, and its genetic deletion depleted a subset of aSMA-expressing CAFs and impaired tumor progression in vivo. The addition of wild-type, but not Endo180-deficient, CAFs in coimplantation studies restricted CD8+ T-cell intratumoral infiltration, and tumors in Endo180 knockout mice exhibited increased CD8+ T-cell infiltration and enhanced sensitivity to ICB compared with tumors in wild-type mice. Clinically, in a trial of melanoma patients, high MRC2 mRNA levels in tumors were associated with a poor response to aPD-1 therapy, highlighting the potential benefits of therapeutically targeting a specific CAF subpopulation in breast and other CAF-rich cancers to improve clinical responses to immunotherapy

Quantum Hall ferromagnets, cooperative transport anisotropy, and the random field Ising model

We discuss the behaviour of a quantum Hall system when two Landau levels with opposite spin and combined filling factor near unity are brought into energetic coincidence using an in-plane component of magnetic field. We focus on the interpretation of recent experiments under these conditions [Zeitler et al, Phys. Rev. Lett. 86, 866 (2001); Pan et al, Phys. Rev. B 64, 121305 (2001)], in which a large resistance anisotropy develops at low temperatures. Modelling the systems involved as Ising quantum Hall ferromagnets, we suggest that this transport anisotropy reflects domain formation induced by a random field arising from isotropic sample surface roughness.Comment: 4 pages, submitted to Physical Review

Conductance fluctuations at the integer quantum Hall plateau transition

We study numerically conductance fluctuations near the integer quantum Hall effect plateau transition. The system is presumed to be in a mesoscopic regime, with phase coherence length comparable to the system size. We focus on a two-terminal conductance G for square samples, considering both periodic and open boundary conditions transverse to the current. At the plateau transition, G is broadly distributed, with a distribution function close to uniform on the interval between zero and one in units of e^2/h. Our results are consistent with a recent experiment by Cobden and Kogan on a mesoscopic quantum Hall effect sample.Comment: minor changes, 5 pages LaTex, 7 postscript figures included using epsf; to be published Phys. Rev. B 55 (1997

Optical properties of metallic (III,Mn)V ferromagnetic semiconductors in the infrared to visible range

We report on a study of the ac conductivity and magneto-optical properties of metallic ferromagnetic (III,Mn)V semiconductors in the infrared to visible spectrum. Our analysis is based on the successful kinetic exchange model for (III,Mn)V ferromagnetic semiconductors. We perform the calculations within the Kubo formalism and treat the disorder effects pertubatively within the Born approximation, valid for the metallic regime. We consider an eight-band Kohn-Luttinger model (six valence bands plus two conduction bands) as well as a ten-band model with additional dispersionless bands simulating phenomenologically the upper-mid-gap states induced by antisite and interstitial impurities. These models qualitatively account for optical-absorption experiments and predict new features in the mid-infrared Kerr angle and magnetic-circular-dichroism properties as a function of Mn concentration and free carrier density.Comment: 10 pages, 7 figures, some typos correcte