A 60-GHz point-to-multipoint millimeter-wave fiber-radio communication system

A 60-GHz point-to-multipoint wireless access link with data rate of 156 Mb/s incorporating 60-GHz transceiver modules and full-duplex fiber-optic millimeter-wave transmission is developed for short-range applications such as indoor wireless local area networks and intelligent transport systems. For compact system configuration, a small-size millimeter-wave transceiver module with planar antennas is developed. The transceiver module is based on broadband planar integration and packaging of millimeter-wave circuits. The RF output power is +10 dBm and the measured 3-dB antenna beamwidth is 30/spl deg/. The total size of the developed 60-GHz transceiver module, except input and output connectors, is 50 mm /spl times/ 75 mm /spl times/ 35 mm. A point-to-point full duplex fiber-optic configuration is extended to the scheme with multiple access points (APs) by using a tree coupler and a dense wavelength division multiplexing multiplexer. The AP has a simple configuration without frequency conversion. The bit error rate and packet error rate performances of the 60-GHz fiber-radio access link are evaluated. Furthermore, the effect of the extension to the scheme with multiple APs is investigated.     

Enhanced carrier confinement in AlInGaN-InGaN quantum wells in near ultraviolet light-emitting diodes

To increase carrier confinement, the GaN barrier layer was substituted with an AlInGaN quaternary barrier layer which was lattice-matched to GaN in the GaN-InGaN multiple quantum wells (MQWs). Photoluminescence (PL) and high-resolution X-ray diffraction measurements showed that the AlInGaN barrier layer has a higher bandgap energy than the originally used GaN barrier layer. The PL intensity of the five periods of AlInGaN-InGaN MQWs was increased by three times compared to that of InGaN-GaN MQWs. The electroluminescence (EL) emission peak of AlInGaN-InGaN MQWs ultraviolet light-emitting diode (UV LED) was blue-shifted, compared to a GaN-InGaN MQWs UV LED and the integrated EL intensity of the AlInGaN-InGaN MQWs UV LED increased linearly up to 100 mA. These results indicated that the AlInGaN-InGaN MQWs UV LED has a stronger carrier confinement than a GaN-InGaN MQWs UV LED due to the larger barrier height of the AlInGaN barrier layer compared to a GaN barrier layer.     

High-performance 94-GHz single balanced mixer using 70-nm MHEMTs and surface micromachined technology

We reported 94-GHz, low conversion loss, and high isolation single balanced active gate mixer based on 70-nm gate length InGaAs/InAlAs metamorphic high-electron mobility transistors (MHEMTs). This mixer showed that the conversion loss and isolation characteristics were 2.5/spl sim/3.5 dB and under -29 dB in the range of 92.95/spl sim/94.5 GHz, respectively. The low conversion loss of the mixer is mainly attributed to the high-performance of the MHEMTs exhibiting a maximum drain current density of 607 mA/mm, an extrinsic transconductance of 1015 mS/mm, a current gain cutoff frequency (f/sub t/) of 330 GHz, and a maximum oscillation frequency (f/sub max/) of 425 GHz. High isolation characteristics are due to hybrid ring coupler which adopted dielectric-supported air-gapped microstrip line structure using surface micromachined technology. To our knowledge, these results are the best performance demonstrated from 94 GHz single balanced mixer utilizing GaAs-based HEMTs in terms of conversion loss as well as isolation characteristics.     

High-Resolution Infrared-Vacuum Ultraviolet Photoion and Pulsed Field Ionization-Photoelectron Methods for Spectroscopic Studies of Neutrals and Cations

We show that by scanning the frequency of a single mode infrared (IR) optical parametric oscillator (IR-OPO) laser to excite the molecular species of interest and fixing the frequency of a vacuum ultraviolet (VUV) laser to photoionize the IR excited species, high-resolution IR spectra of polyatomic neutrals can be obtained with high sensitivity. The fact that this IR-VUV-photoion (IR-VUV-PI) method is based on VUV photoionization probe, and thus, allows the identification of the neutral IR absorber, makes it applicable for IR spectroscopy measurements of isotopemers, radicals, and clusters, which usually exist as impure samples. The highly resolved IR-VUV-PI measurements achieved using the single mode IR-OPO laser have made possible the selection of single rovibrational states of CH3X (X=Br and I), C2H4, and C3H4 for VUV-pulsed field ionization-photoelectron (VUV-PFI-PE) measurements, resulting in rovibrationally resolved photoelectron spectra for these polyatomic molecules. These experiments show that the signal-to-noise ratios of the IR-VUV-PI and IR-VUV-PFI-PE spectra obtained by employing the high-resolution IR-OPO laser are significantly higher than those observed in previous IR-VUV-PI and IR-VUV-PFI-PE studies using a low-resolution IR-OPO laser. Further improvement in sensitivity of IR-VUV-PI and IR-VUV-PFI-PE measurements by using the collinear arrangement of IR-VUV lasers and molecular beam is discussed.     

Decoding ‘Maximum Entropy’ Deconvolution

For over five decades, the mathematical procedure termed “maximum entropy” (M-E) has been used to deconvolve structure in spectra, optical and otherwise, although quantitative measures of performance remain unknown. Here, we examine this procedure analytically for the lowest two orders for a Lorentzian feature, obtaining expressions for the amount of sharpening and identifying how spurious structures appear. Illustrative examples are provided. These results enhance the utility of this widely used deconvolution approach to spectral analysis.     

Establishment of a humanized animal model of systemic sclerosis in which T helper-17 cells from patients with systemic sclerosis infiltrate and cause fibrosis in the lungs and skin

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by inflammation, microangiopathy, and progressive fibrosis in the skin and internal organs. To evaluate the pathophysiologic mechanisms and efficacies of potential therapeutics for SSc, a preclinical model recapitulating the disease phenotypes is needed. Here, we introduce a novel animal model for SSc using immunodeficient mice injected with peripheral blood mononuclear cells (PBMCs) from SSc patients. Human PBMCs acquired from SSc patients and healthy controls were transferred into NOD.Cg-Prkdc^scidIl2rg^tm1Wjl (NSG) mice with concurrent bleomycin injection. Blood, skin, and lung tissues were acquired and analyzed after PBMC engraftment. In addition, we investigated whether the humanized murine model could be used to assess the efficacy of potential therapeutics for SSc. Human PBMCs from SSc patients and healthy controls were engrafted into the blood, skin, and lung tissues of NSG mice. Histological analysis of affected tissues from mice treated with SSc PBMCs (SSc hu-mice) demonstrated substantial inflammation, fibrosis and vasculopathy with human immune cell infiltration and increased expression of IL-17, TGF-β, CCL2, CCL3, and CXCL9. The proportions of circulating and tissue-infiltrating T helper 17 (Th17) cells were elevated in SSc hu-mice. These cells showed increased expression of CXCR3 and phosphorylated STAT3. SSc hu-mice treated with rebamipide and other potential Th17-cell-modulating drugs presented significantly reduced tissue fibrosis. Mice injected with patient-derived PBMCs show promise as an animal model of SSc.Subject terms: Autoimmunity, Autoimmune diseases     

BMS794833 inhibits macrophage efferocytosis by directly binding to MERTK and inhibiting its activity

Myeloid epithelial reproductive proto-oncogene tyrosine kinase (MERTK) plays an essential role in modulating cancer immune tolerance by regulating macrophage efferocytosis. Studies are underway to develop small-molecule chemicals that inhibit MERTK as cancer immunotherapeutic agents, but these efforts are in their early stages. This study identified BMS794833, whose primary targets are MET and VEGFR2, as a potent MERTK inhibitor and developed a real-time efferocytosis monitoring system. The X-ray cocrystal structure revealed that BMS794833 was in contact with the ATP-binding pocket and the allosteric back pocket, rendering MERTK inactive. Homogeneous time-resolved fluorescence kinetic and Western blotting analyses showed that BMS794833 competitively inhibited MERTK activity in vitro and inhibited the autophosphorylation of MERTK in macrophages. We developed a system to monitor MERTK-dependent efferocytosis in real time, and using this system, we confirmed that BMS794833 significantly inhibited the efferocytosis of differentiated macrophages. Finally, BMS794833 significantly inhibited efferocytosis in vivo in a mouse model. These data show that BMS794833 is a type II MERTK inhibitor that regulates macrophage efferocytosis. In addition, the real-time efferocytosis monitoring technology developed in this study has great potential for future applications.Subject terms: Biochemistry, Cell biology     

NRBF2-mediated autophagy contributes to metabolite replenishment and radioresistance in glioblastoma

Overcoming therapeutic resistance in glioblastoma (GBM) is an essential strategy for improving cancer therapy. However, cancer cells possess various evasion mechanisms, such as metabolic reprogramming, which promote cell survival and limit therapy. The diverse metabolic fuel sources that are produced by autophagy provide tumors with metabolic plasticity and are known to induce drug or radioresistance in GBM. This study determined that autophagy, a common representative cell homeostasis mechanism, was upregulated upon treatment of GBM cells with ionizing radiation (IR). Nuclear receptor binding factor 2 (NRBF2)—a positive regulator of the autophagy initiation step—was found to be upregulated in a GBM orthotopic xenograft mouse model. Furthermore, ATP production and the oxygen consumption rate (OCR) increased upon activation of NRBF2-mediated autophagy. It was also discovered that changes in metabolic state were induced by alterations in metabolite levels caused by autophagy, thereby causing radioresistance. In addition, we found that lidoflazine—a vasodilator agent discovered through drug repositioning—significantly suppressed IR-induced migration, invasion, and proliferation by inhibiting NRBF2, resulting in a reduction in autophagic flux in both in vitro models and in vivo orthotopic xenograft mouse models. In summary, we propose that the upregulation of NRBF2 levels reprograms the metabolic state of GBM cells by activating autophagy, thus establishing NRBF2 as a potential therapeutic target for regulating radioresistance of GBM during radiotherapy.Subject terms: Cancer metabolism, Prognostic markers     

KLHL3 deficiency in mice ameliorates obesity,insulin resistance,and nonalcoholic fatty liver disease by regulating energy expenditure

Obesity is a growing global epidemic that can cause serious adverse health consequences, including insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD). Obesity development can be attributed to energy imbalance and metabolic inflexibility. Here, we demonstrated that lack of Kelch-like protein 3 (KLHL3) mitigated the development of obesity, IR, and NAFLD by increasing energy expenditure. KLHL3 mutations in humans cause Gordon’s hypertension syndrome; however, the role of KLHL3 in obesity was previously unknown. We examined differences in obesity-related parameters between control and Klhl3^−/− mice. A significant decrease in body weight concomitant with fat mass loss and improved IR and NAFLD were observed in Klhl3^−/− mice fed a high-fat (HF) diet and aged. KLHL3 deficiency inhibited obesity, IR, and NAFLD by increasing energy expenditure with augmentation of O₂ consumption and CO₂ production. Delivering dominant-negative (DN) Klhl3 using adeno-associated virus into mice, thereby dominantly expressing DN-KLHL3 in the liver, ameliorated diet-induced obesity, IR, and NAFLD. Finally, adenoviral overexpression of DN-KLHL3, but not wild-type KLHL3, in hepatocytes revealed an energetic phenotype with an increase in the oxygen consumption rate. The present findings demonstrate a novel function of KLHL3 mutation in extrarenal tissues, such as the liver, and may provide a therapeutic target against obesity and obesity-related diseases.Subject terms: Obesity, Homeostasis     

Cleistocalyx nervosum var. paniala Berry Promotes Antioxidant Response and Suppresses Glutamate-Induced Cell Death via SIRT1/Nrf2 Survival Pathway in Hippocampal HT22 Neuronal Cells

Excessive glutamate neurotransmitters result in oxidative neurotoxicity, similar to neurodegeneration. An indigenous berry of Thailand, Cleistocalyx nervosum var. paniala (CNP), has been recognized for its robust antioxidants. We investigated the effects and mechanisms of CNP fruit extracts on antioxidant-related survival pathways against glutamate-induced neurotoxicity. The extract showed strong antioxidant capability and had high total phenolic and flavonoid contents, particularly resveratrol. Next, the protective effects of the CNP extract or resveratrol on the glutamate-induced neurotoxicity were examined in HT22 hippocampal cells. Our investigation showed that the pretreatment of cells with the CNP extract or resveratrol attenuated glutamate-induced neuronal death via suppression of apoptosis cascade by inhibiting the levels of cleaved- and pro-caspase-3 proteins. The CNP extract and resveratrol suppressed the intracellular ROS by increasing the mRNA expression level of antioxidant enzymes (SODs, GPx1, and CAT). We found that this extract and resveratrol significantly increased SIRT1 expression as a survival-related protein. Moreover, they also promoted the activity of the Nrf2 protein translocation into the nucleus and could bind to the promoter containing the antioxidant response element, inducing the expression of the downstream GPx1-antioxidant protein. Our data illustrate that the CNP extract and resveratrol inhibit apoptotic neuronal death via glutamate-induced oxidative neurotoxicity in HT22 cells through the activation of the SIRT1/Nrf2 survival mechanism.