Antimony doping of Si layers grown by solid-phase epitaxy

We report here that layers of Si formed by solid-phase epitaxial growth (SPEG) can be doped intentionally. The sample consists initially of an upper layer of amorphous Si (~1 µm thick), a very thin intermediate layer of Sb (nominally 5 Å), and a thin lower layer of Pd (~500 Å), all electron-gun deposited on top of a single-crystal substrate (1–10 Ω cm, p type, orientation). After a heating cycle which induces epitaxial growth, electrically active Sb atoms are incorporated into the SPEG layer, as shown by the following facts: (a) the SPEG layer forms a p-n junction against the p-type substrate, (b) the Hall effect indicates strong n-type conduction of the layer, and (c) Auger electron spectra reveal the presence of Sb in the layer

Correction to: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma

© 2018 The Author(s). Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

Kinetic roughening of surfaces: Derivation, solution and application of linear growth equations

We present a comprehensive analysis of a linear growth model, which combines the characteristic features of the Edwards--Wilkinson and noisy Mullins equations. This model can be derived from microscopics and it describes the relaxation and growth of surfaces under conditions where the nonlinearities can be neglected. We calculate in detail the surface width and various correlation functions characterizing the model. In particular, we study the crossover scaling of these functions between the two limits described by the combined equation. Also, we study the effect of colored and conserved noise on the growth exponents, and the effect of different initial conditions. The contribution of a rough substrate to the surface width is shown to decay universally as $w_i(0) (\xi_s/\xi(t))^{d/2}$, where $\xi(t) \sim t^{1/z}$ is the time--dependent correlation length associated with the growth process, $w_i(0)$ is the initial roughness and $\xi_s$ the correlation length of the substrate roughness, and $d$ is the surface dimensionality. As a second application, we compute the large distance asymptotics of the height correlation function and show that it differs qualitatively from the functional forms commonly used in the intepretation of scattering experiments.Comment: 28 pages with 4 PostScript figures, uses titlepage.sty; to appear in Phys. Rev.

GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients

GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) within the subendothelial spaces and shuttles it to the capillary lumen. The GPIHBP1-bound LPL is essential for the margination of triglyceride-rich lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRLs to proceed. In peripheral tissues, the intravascular processing of TRLs by the GPIHBP1-LPL complex is crucial for generating lipid nutrients for adjacent parenchymal cells. GPIHBP1 is absent in capillaries of the brain, which uses glucose for fuel; however, GPIHBP1 is expressed in capillaries of mouse and human gliomas. Importantly, the GPIHBP1 in glioma capillaries captures locally produced LPL. We document, by NanoSIMS imaging, that TRLs marginate along glioma capillaries and that there is uptake of TRL-derived lipid nutrients by surrounding glioma cells. Thus, GPIHBP1 expression in gliomas facilitates TRL processing and provides a source of lipid nutrients for glioma cells

Epidermal Growth Factor Receptor Activation in Glioblastoma through Novel Missense Mutations in the Extracellular Domain

Background: Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy. Methods and Findings: Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR) kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132) of glioblastomas and 12.5% (1/ 8) of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors. Conclusions: Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma