2.4 GHz GaN HEMT Class-F Synchronous Rectifier Using an Independent Second Harmonic Tuning Circuit.

This paper proposes a class-F synchronous rectifier using an independent second harmonic tuning circuit for the power receiver of 2.4 GHz wireless power transmission systems. The synchronous rectifier can be designed by inverting the RF output port to the RF input port of the pre-designed class-F power amplifier based on time reversal duality. The design of the class-F power amplifier deploys an independent second harmonic tuning circuit in the matching networks to individually optimize the impedances of the fundamental and the second harmonic. The synchronous rectifier at the 2.4 GHz frequency is designed and implemented using a 6 W gallium nitride high electron mobility transistor (GaN HEMT). Peak RF-dc conversion efficiency of the rectifier of 69.6% is achieved with a dc output power of about 7.8 W, while the peak drain efficiency of the class-F power amplifier is 72.8%.

Restoration of miR-29b exerts anti-cancer effects on glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is known as one of the most fatal forms of cancer. MicroRNAs have been widely implicated in the regulation of mammalian development and pathogenesis. The brain-enriched miR-29 subfamilies are known to be exclusively expressed in the developing brain, and they are aberrantly down-regulated in GBM. This study aims to elucidate the role of miR-29b in GBM development and the feasibility of therapeutic targeting using conjugated nanoparticles. METHODS: After confirmation of miR-29b expression levels in GBM tissues by analysis of open source data, the anticancer effect of miR-29b was tested by the introduction of syn-hsa-miR-29b-3p in the A172 GBM cell line. In vitro studies of cell viability and apoptosis and ex vivo study using GBM tissue slice cultures from 3 patients and nanoparticle delivery of miR-29b were performed. RESULTS: We discovered an increase in apoptotic cell populations with the introduction of miR-29b in the GBM cell line. An established human-derived GBM tissue slice culture system confirmed the anticancer effect of miR-29b-conjugated nanoparticles. Using PCR array, we found that exogenous miR-29b inhibits the expression of COL1A2, COL3A1, COL4A1, ELN, ITGA11, MMP24, and SPARC, which mediates an anticancer effect. CONCLUSIONS: miR-29b may serve as a putative therapeutic molecule when its expression is restored using a nanoparticle delivery system in GBM.

Intrinsic spherical smoothing method based on generalized Bézier curves and sparsity inducing penalization.

This study examines an intrinsic penalized smoothing method on the 2-sphere. We propose a method based on the spherical Bézier curves obtained using a generalized de Casteljau algorithm to provide a degree-based regularity constraint to the spherical smoothing problem. A smooth Bézier curve is found by minimizing the least squares criterion under the regularization constraint. The de Casteljau algorithm constructs higher-order Bézier curves in a recursive manner using linear Bézier curves. We introduce a local penalization scheme based on a penalty function that regularizes the velocity differences in consecutive linear Bézier curves. The imposed penalty induces sparsity on the control points so that the proposed method determines the number of control points, or equivalently the order of the Bézier curve, in a data-adaptive way. An efficient Riemannian block coordinate descent algorithm is devised to implement the proposed method. Numerical studies based on real and simulated data are provided to illustrate the performance and properties of the proposed method. The results show that the penalized Bézier curve adapts well to local data trends without compromising overall smoothness.

TGF-ß signaling in endothelial cells, but not neuroepithelial cells, is essential for cerebral vascular development.

The various organs of the body harbor blood vessel networks that display unique structural and functional features; however, the mechanisms that control organ-specific vascular development and physiology remain mostly unknown. In the developing mouse brain, αvß8 integrin-mediated TGF-ß activation and signaling is essential for normal blood vessel growth and sprouting. Whether integrins activate TGF-ß signaling pathways in vascular endothelial cells (ECs), neural cells, or both, has yet to be determined. Here, we have generated and characterized mice in which TGF-ß receptors are specifically deleted in neuroepithelial cells via Nestin-Cre, or in ECs via a novel Cre transgenic strain (Alk1(GFPCre)) in which Cre is expressed under control of the endogenous activin receptor-like kinase 1 (Alk1) promoter. We report that deletion of Tgfbr2 in the neuroepithelium does not impact brain vascular development. In contrast, selective deletion of the Tgfbr2 or Alk5 genes in ECs result in embryonic lethality because of brain-specific vascular pathologies, including blood vessel morphogenesis and intracerebral hemorrhage. These data reveal for the first time that αvß8 integrin-activated TGF-ßs regulate angiogenesis in the developing brain via paracrine signaling to ECs.

FZD10-Gα13 signalling axis points to a role of FZD10 in CNS angiogenesis.

Among the 10 Frizzled (FZD) isoforms belonging to the Class F of G protein-coupled receptors (GPCRs), FZD10 remains the most enigmatic. FZD10 shows homology to FZD4 and FZD9 and was previously implicated in both ß-catenin-dependent and -independent signalling. In normal tissue, FZD10 levels are generally very low; however, its upregulation in synovial carcinoma has attracted some attention for therapy. Our findings identify FZD10 as a receptor interacting with and signalling through the heterotrimeric G protein Gα13 but not Gα12, Gαi1, GαoA, Gαs, or Gαq. Stimulation with the FZD agonist WNT induced the dissociation of the Gα13 protein from FZD10, and led to global Gα12/13-dependent cell changes assessed by dynamic mass redistribution measurements. Furthermore, we show that FZD10 mediates Gα12/13 activation-dependent induction of YAP/TAZ transcriptional activity. In addition, we show a distinct expression of FZD10 in embryonic CNS endothelial cells at E11.5-E14.5. Given the well-known importance of Gα13 signalling for the development of the vascular system, the selective expression of FZD10 in brain vascular endothelial cells points at a potential role of FZD10-Gα13 signalling in CNS angiogenesis.

A subpopulation of cancer stem cells identifies radiographic characteristics in glioblastoma.

Cancer stem cells (CSCs), defined by CD133 expression, harbor heterogeneous subpopulations of cells, including endothelial progenitor cells (EPCs). This study aimed to investigate whether a subpopulation of CSCs could affect the radiographic characteristics of glioblastoma. Tissue samples from 10 patients newly diagnosed with glioblastoma were selected according to the radiographic characteristics of their tumors. The patients were divided into two groups based on preoperative magnetic resonance imaging demonstrating contrast enhancement, necrosis and infiltrative patterns: the enhancement/necrosis group (E/N, n=5) and the non-enhancement/infiltration group (NE/I, n=5). Flow cytometry was used to assess the CSCs while immunohistochemistry was used to study microvessel density and the proliferation index. The EPC (CD34+/CD133+) fraction in CSCs (CD133+) was larger in the NE/I group. However, there was little difference in the angiogenic activity assessed using microvessel density between the two groups. The proliferation index (assessed using the antibody Ki-67) was higher in the E/N group and was negatively correlated with the EPC fraction. The non-EPC (CD34-/CD133+) fraction is a major factor responsible for radiographic characteristics of contrast enhancement, thus establishing an association between a subpopulation fraction of CSCs and radiographic characteristics in glioblastoma. Therefore, the simple non-invasive assessment of studying contrast enhancement lesions in glioblastomas may be used to estimate CSC subpopulations.

Glioblastoma angiogenesis and tumor cell invasiveness are differentially regulated by ß8 integrin.

Glioblastoma multiforme (GBM) is a highly invasive brain tumor that develops florid microvascular proliferation and hemorrhage. However, mechanisms that favor invasion versus angiogenesis in this setting remain largely uncharacterized. Here, we show that integrin ß8 is an essential regulator of both GBM-induced angiogenesis and tumor cell invasiveness. Highly angiogenic and poorly invasive tumors expressed low levels of ß8 integrin, whereas highly invasive tumors with limited neovascularization expressed high levels of ß8 integrin. Manipulating ß8 integrin protein levels altered the angiogenic and invasive growth properties of GBMs, in part, reflected by a diminished activation of latent TGFßs, which are extracellular matrix protein ligands for ß8 integrin. Taken together, these results establish a role for ß8 integrin in differential control of angiogenesis versus tumor cell invasion in GBM. Our findings suggest that inhibiting ß8 integrin or TGFß signaling may diminish tumor cell invasiveness during malignant progression and following antivascular therapies.

Beta8 integrin regulates neurogenesis and neurovascular homeostasis in the adult brain.

Central nervous system (CNS) neurovascular units are multicellular complexes consisting of neural cells, blood vessels and a milieu of extracellular matrix (ECM) proteins. ECM-mediated adhesion and signaling events within neurovascular units probably contribute to proper CNS development and physiology; however, the molecular mechanisms that control these events remain largely undetermined. Previous studies from our group and others showed that ablation of the ECM receptor, alphavbeta8 integrin, in neural progenitor cells (NPCs) of the embryonic mouse brain results in severe developmental neurovascular pathologies and premature death. Here, we have investigated the functions for this integrin in the adult brain by studying mice harboring a homozygous-null beta8 gene mutation generated on an outbred background that permits survival for several months. We show that adult beta8-/- mice display widespread defects in neurovascular unit homeostasis, including increased numbers of intracerebral blood vessels with pronounced perivascular astrogliosis. Furthermore, in neurogenic regions of the adult brain, where NPCs cluster around blood vessels in neurovascular niches, beta8 integrin is essential for normal control of NPC proliferation and survival. Analysis of NPCs cultured ex vivo reveals that the growth and survival defects correlate, in part, with diminished integrin-mediated activation of latent transforming growth factor beta1 (TGFbeta1), which is an ECM protein ligand for alphavbeta8 integrin. Collectively, these data identify essential functions for beta8 integrin in regulating neurovascular unit physiology in the post-natal mouse brain.