Influence of interface structure on electronic properties and Schottky barriers in Fe/GaAs magnetic junctions

The electronic and magnetic properties of Fe/GaAs(001) magnetic junctions are investigated using first-principles density-functional calculations. Abrupt and intermixed interfaces are considered, and the dependence of charge transfer, magnetization profiles, Schottky barrier heights, and spin polarization of densities of states on interface structure is studied. With As-termination, an abrupt interface with Fe is favored, while Ga-terminated GaAs favors the formation of an intermixed layer with Fe. The Schottky barrier heights are particularly sensitive to the abruptness of the interface. A significant density of states in the semiconducting gap arises from metal interface states. These spin-dependent interface states lead to a significant minority spin polarization of the density of states at the Fermi level that persists well into the semiconductor, providing a channel for the tunneling of minority spins through the Schottky barrier. These interface-induced gap states and their dependence on atomic structure at the interface are discussed in connection with potential spin-injection applications.Comment: 9 pages, 9 figures, to appear in PR

Deterministic Separation of Cancer Cells from Blood at 10 mL/min

Circulating tumor cells (CTCs) and circulating clusters of cancer and stromal cells have been identified in the blood of patients with malignant cancer and can be used as a diagnostic for disease severity, assess the efficacy of different treatment strategies and possibly determine the eventual location of metastatic invasions for possible treatment. There is thus a critical need to isolate, propagate and characterize viable CTCs and clusters. Here, we present a microfluidic device for mL/min flow rate, continuous-flow capture of viable CTCs from blood using deterministic lateral displacement arrays. We show here that a deterministic bump array can be designed such that it will isolate with efficiency greater than 85% CTCs over a large range in sizes from millimeter volume clinical blood samples in minutes, with no effect on cell vitality so that further culturing and analysis of the cells can be carried out

Induction of Histiocytic Sarcoma in Mouse Skeletal Muscle

Myeloid sarcomas are extramedullary accumulations of immature myeloid cells that may present with or without evidence of pathologic involvement of the bone marrow or peripheral blood, and often coincide with or precede a diagnosis of acute myeloid leukemia (AML). A dearth of experimental models has hampered the study of myeloid sarcomas and led us to establish a new system in which tumor induction can be evaluated in an easily accessible non-hematopoietic tissue compartment. Using ex-vivo transduction of oncogenic Kras(G12V) into p16/p19−/− bone marrow cells, we generated transplantable leukemia-initiating cells that rapidly induced tumor formation in the skeletal muscle of immunocompromised NOD.SCID mice. In this model, murine histiocytic sarcomas, equivalent to human myeloid sarcomas, emerged at the injection site 30–50 days after cell implantation and consisted of tightly packed monotypic cells that were CD48+, CD47+ and Mac1+, with low or absent expression of other hematopoietic lineage markers. Tumor cells also infiltrated the bone marrow, spleen and other non-hematopoietic organs of tumor-bearing animals, leading to systemic illness (leukemia) within two weeks of tumor detection. P16/p19−/−; Kras(G12V) myeloid sarcomas were multi-clonal, with dominant clones selected during secondary transplantation. The systemic leukemic phenotypes exhibited by histiocytic sarcoma-bearing mice were nearly identical to those of animals in which leukemia was introduced by intravenous transplantation of the same donor cells. Moreover, murine histiocytic sarcoma could be similarly induced by intramuscular injection of MLL-AF9 leukemia cells. This study establishes a novel, transplantable model of murine histiocytic/myeloid sarcoma that recapitulates the natural progression of these malignancies to systemic disease and indicates a cell autonomous leukemogenic mechanism.Stem Cell and Regenerative Biolog

Quantitative Assessment of Experimental Ocular Inflammatory Disease

Ocular inflammation imposes a high medical burden on patients and substantial costs on the health-care systems that mange these often chronic and debilitating diseases. Many clinical phenotypes are recognized and classifying the severity of inflammation in an eye with uveitis is an ongoing challenge. With the widespread application of optical coherence tomography in the clinic has come the impetus for more robust methods to compare disease between different patients and different treatment centers. Models can recapitulate many of the features seen in the clinic, but until recently the quality of imaging available has lagged that applied in humans. In the model experimental autoimmune uveitis (EAU), we highlight three linked clinical states that produce retinal vulnerability to inflammation, all different from healthy tissue, but distinct from each other. Deploying longitudinal, multimodal imaging approaches can be coupled to analysis in the tissue of changes in architecture, cell content and function. This can enrich our understanding of pathology, increase the sensitivity with which the impacts of therapeutic interventions are assessed and address questions of tissue regeneration and repair. Modern image processing, including the application of artificial intelligence, in the context of such models of disease can lay a foundation for new approaches to monitoring tissue health

Beyond Eliashberg superconductivity in MgB2: anharmonicity, two-phonon scattering, and multiple gaps

Density-functional calculations of the phonon spectrum and electron-phonon coupling in MgB$_2$ are presented. The $E_{2g}$ phonons, which involve in-plane B displacements, couple strongly to the $p_{x,y}$ electronic bands. The isotropic electron-phonon coupling constant is calculated to be about 0.8. Allowing for different order parameters in different bands, the superconducting $\lambda$ in the clean limit is calculated to be significantly larger. The $E_{2g}$ phonons are strongly anharmonic, and the non-linear contribution to the coupling between the $E_{2g}$ modes and the p$_{x,y}$ bands is significant.Comment: 4 pages, 3 figure

SigFuge: Single gene clustering of RNA-seq reveals differential isoform usage among cancer samples

High-throughput sequencing technologies, including RNA-seq, have made it possible to move beyond gene expression analysis to study transcriptional events including alternative splicing and gene fusions. Furthermore, recent studies in cancer have suggested the importance of identifying transcriptionally altered loci as biomarkers for improved prognosis and therapy. While many statistical methods have been proposed for identifying novel transcriptional events with RNA-seq, nearly all rely on contrasting known classes of samples, such as tumor and normal. Few tools exist for the unsupervised discovery of such events without class labels. In this paper, we present SigFuge for identifying genomic loci exhibiting differential transcription patterns across many RNA-seq samples. SigFuge combines clustering with hypothesis testing to identify genes exhibiting alternative splicing, or differences in isoform expression. We apply SigFuge to RNA-seq cohorts of 177 lung and 279 head and neck squamous cell carcinoma samples from the Cancer Genome Atlas, and identify several cases of differential isoform usage including CDKN2A, a tumor suppressor gene known to be inactivated in a majority of lung squamous cell tumors. By not restricting attention to known sample stratifications, SigFuge offers a novel approach to unsupervised screening of genetic loci across RNA-seq cohorts. SigFuge is available as an R package through Bioconductor

Tunable and Transferable Diamond Membranes for Integrated Quantum Technologies

Color centers in diamond are widely explored as qubits in quantum technologies. However, challenges remain in the effective and efficient integration of these diamond-hosted qubits in device heterostructures. Here, nanoscale-thick uniform diamond membranes are synthesized via "smart-cut" and isotopically (12C) purified overgrowth. These membranes have tunable thicknesses (demonstrated 50 to 250 nm), are deterministically transferable, have bilaterally atomically flat surfaces (Rq ≤ 0.3 nm), and bulk-diamond-like crystallinity. Color centers are synthesized via both implantation and in situ overgrowth incorporation. Within 110-nm-thick membranes, individual germanium-vacancy (GeV-) centers exhibit stable photoluminescence at 5.4 K and average optical transition line widths as low as 125 MHz. The room temperature spin coherence of individual nitrogen-vacancy (NV-) centers shows Ramsey spin dephasing times (T2*) and Hahn echo times (T2) as long as 150 and 400 μs, respectively. This platform enables the straightforward integration of diamond membranes that host coherent color centers into quantum technologies

The PREVIEW_NZ cohort

Publisher Copyright: © 2024 The AuthorsAim: Accumulation of circulating branched-chain amino acids (BCAA) is a hallmark feature of impaired insulin sensitivity. As intracellular BCAA catabolism is dependent on glycine availability, we hypothesised that the concurrent measurement of circulating glycine and BCAA may yield a stronger association with markers of insulin sensitivity than either BCAA or glycine alone. This study therefore examined the correlative relationships of BCAA, BCAA and glycine together, plus glycine alone on insulin sensitivity-related markers before and after an 8-week low energy diet (LED) intervention. Methods: This is a secondary analysis of the PREVIEW (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World) Study New Zealand sub-cohort. Eligible participants with pre-diabetes at baseline who achieved ≥8 % body weight loss following an LED intervention were included, of which 167 paired (Week 0 and Week 8) blood samples were available for amino acid analysis. Glycemic and other data were retrieved from the PREVIEW consortium database. Repeated measures linear mixed models were used to test the association between amino acids and insulin sensitivity-related markers (HOMA2-IR, glucose, insulin, and C-peptide). Results: Elevated BCAA was associated with impaired insulin sensitivity (p < 0.05), with strength of association (ηp2) almost doubled when glycine was added to the model. However, glycine in isolation was not associated with insulin sensitivity-related markers. The magnitude (β-estimates) of positive association between BCAA and HOMA2-IR, and inverse association between glycine and HOMA2-IR, increased when body weight was higher (Body weight∗BCAA, Body weight∗glycine, p < 0.05, both). Conclusion: Low serum glycine strengthened the association between BCAA and impaired insulin sensitivity. Given that glycine is necessary to facilitate intracellular BCAA catabolism, measurement of glycine is necessary to complement BCAA analysis to comprehensively understand the contribution of amino acid metabolism in insulin sensitivity. Clinical trial registration: This study was registered with ClinicalTrials.gov (NCT01777893).publishersversionpublishe