This paper presents three millimeter-wave (mm-wave) continuous-mode power amplifiers (PAs) for fifth-generation (5G) MIMO applications, including a two-stage differential continuous-mode Class-F −1 ...PA in 130-nm SiGe process, a single-stage differential continuous-mode hybrid Class-F/F −1 PA in 45-nm SOI CMOS process, and a two-stage differential continuous-mode hybrid Class-F/F −1 PA in 45-nm SOI CMOS process. The first PA design covers 19-29.5 GHz, while the other two designs cover 23-41 GHz, all covering multiple 5G bands (24/28/37/39 GHz). All the presented PA designs are based on a proposed transformer-based continuous-mode harmonically tuned PA output network. This network provides proper harmonic impedance terminations for the fundamental, second-order, and third-order harmonic impedances, which supports continuous-mode Class-F −1 or hybrid Class-F/F −1 PA operations to achieve ultrawide bandwidth yet high efficiency. The first PA design achieves a wide <inline-formula> <tex-math notation="LaTeX">P_{\mathrm {sat}}~1 </tex-math></inline-formula>-dB bandwidth of 19-29.5 GHz (43.3%) and high peak power-added efficiency (PAE) (43.5%). The second design achieves an ultrawide <inline-formula> <tex-math notation="LaTeX">P_{\mathrm {sat}}~1 </tex-math></inline-formula>-dB bandwidth of 23.5-41 GHz (53.3%) and high peak PAE (46%). Moreover, it achieves 43.4% PAE and 18.6-dBm <inline-formula> <tex-math notation="LaTeX">P_{\mathrm {sat}} </tex-math></inline-formula> at 27 GHz, 40.2% PAE and 18.6-dBm <inline-formula> <tex-math notation="LaTeX">P_{\mathrm {sat}} </tex-math></inline-formula> at 37 GHz, and 41.2% PAE and 18.5-dBm <inline-formula> <tex-math notation="LaTeX">P_{\mathrm {sat}} </tex-math></inline-formula> at 39 GHz, respectively. The third PA design also achieves an ultrawide <inline-formula> <tex-math notation="LaTeX">P_{\mathrm {sat}}~1 </tex-math></inline-formula>-dB bandwidth of 23.5-41 GHz (53.3%) and high peak PAE (43.2%). It achieves 43% PAE and 18.9-dBm <inline-formula> <tex-math notation="LaTeX">P_{\mathrm {sat}} </tex-math></inline-formula> at 27 GHz, 37% PAE and 19-dBm <inline-formula> <tex-math notation="LaTeX">P_{\mathrm {sat}} </tex-math></inline-formula> at 37 GHz, and 36% PAE and 18.9-dBm <inline-formula> <tex-math notation="LaTeX">P_{\mathrm {sat}} </tex-math></inline-formula> at 39 GHz, respectively. Extensive 64-/256-QAM modulation tests demonstrate the high PA linearity. Our proposed PA designs outperform the reported mm-wave silicon-based 5G PAs in terms of high efficiency over an ultrawide bandwidth.
RNA interference (RNAi), a newly developed method in which RNA molecules inhibit gene expression, has recently received considerable research attention. In the development of RNAi-based therapies, ...nanoparticles, which have distinctive size effects along with facile modification strategies and are capable of mediating effective RNAi with targeting potential, are attracting extensive interest.
This review presents an overview of the mechanisms of RNAi molecules in gene therapy and the different nanoparticles used to deliver RNAi molecules; briefly describes the current uses of RNAi in cancer therapy along with the nano-based delivery of RNA molecules in previous studies; and highlights some other carriers that have been applied in clinical settings. Finally, we discuss the nano-based delivery of RNAi therapeutics in preclinical development, including the current status and limitations of anti-cancer treatment.
With the growing number of RNAi therapeutics entering the clinical phase, various nanocarriers are expected to play important roles in the delivery of RNAi molecules for cancer therapeutics.
This article presents a millimeter-wave (mm-wave) transmitter (TX) front-end employing a new inverse outphasing architecture with current-mode power amplifiers (PAs). This study on the conventional ...outphasing operation reveals its strong dependence on its voltage-mode driving source assumption and thus exhibits major limitations at mm-wave, since efficient and linear mm-wave PAs often behave as current sources. To address this challenge, we propose a current-mode inverse outphasing architecture that employs current-mode driving sources and is inherently compatible with mm-wave linear PAs. Moreover, the conventional series outphasing combiner is replaced by a much simpler and low-loss parallel power combining scheme. Closed-form mathematical expressions are derived for both the outphasing and inverse outphasing operations, including the active load modulation, Chireix compensations, and outphasing efficiency, which fundamentally explains the limitations of the conventional approach and the advantages of the inverse outphasing architecture. Further theoretical analysis discovers a circuit duality relationship between outphasing and inverse outphasing architectures, which offers unique circuit intuitions. As a proof-of-concept, we implement a 28-GHz TX front-end using cascode PAs, based on the inverse outphasing architecture. In the measurement, the TX achieves 22.7-dBm saturated output power with 42.6% PA drain efficiency. The TX exhibits effective PA efficiency enhancement at 6-dB power back-off (PBO), validating the high-efficiency inverse outphasing active load modulation. Modulation tests with high-order quadrature amplitude modulation (QAM) signals demonstrate that the TX supports >10-Gb/s high-fidelity complex signals and achieves the state-of-the-art modulation performance.
•Berberine could improve 3×Tg AD mice’s cognitive function.•Berberine could attenuate the hyperphosphorylation of tau.•Berberine could promote autophagic clearance of tau.
Berberine is a natural ...isoquinoline alkaloid isolated from the Rhizoma coptidis. Recent advances in research throw more lights of its beneficial role towards Alzheimer’s disease (AD), including promoting β-amyloid (Aβ) clearance, as well as inhibiting Aβ production in the triple-transgenic mouse model of Alzheimer’s disease (3×Tg AD). However, it remains unclarified if berberine has an effect on tau pathology. According to our study, berberine did not only significantly improve 3×Tg AD mice’s spatial learning capacity and memory retentions, but also attenuated the hyperphosphorylation of tau. via modulating the activity of Akt/glycogen synthase kinase-3β and protein phosphatase 2A. Moreover, berberine reduced the level of tau through an autophagy-based route. It promoted autophagic clearance of tau by enhancing the activity of autophagy via the class III PI3K/beclin-1 pathway. Thus, our results suggest that berberine could mitigate cognitive decline by simultaneously targeting the hyperphosphorylation of tau and the autophagic clearance of tau in AD mice. These findings strongly support berberine as a potential drug candidate for AD.
This study was conducted to test the hypothesis that biochar application can increase rice yield through improving nitrogen (N) uptake and utilization by rice plants under N application conditions. A ...pot experiment was done with a hybrid rice cultivar grown on a Fe-leachi-Stagnic Anthrosols with and without biochar application. The N fertilizer used was ¹⁵N-labeled urea. Results showed that biochar application resulted in 23–27 % increase in fertilizer N uptake by rice plants and consequently 8–10 % increase in grain yield. The higher fertilizer N uptake under biochar application was associated with a reduced fertilizer N loss. Fertilizer N loss rate was reduced by 9–10 % by applying biochar. We suggest that further studies are needed to assess the short-term and long-term effects of different biochars on N uptake and utilization by rice under field conditions.
The scaling of the plasmoid instability maximum linear growth rate with respect to the Lundquist number S in a Sweet-Parker current sheet, , indicates that at high S, the current sheet will break ...apart before it approaches the Sweet-Parker width. Therefore, a proper description for the onset of the plasmoid instability must incorporate the evolving process of the current sheet. We carry out a series of two-dimensional simulations and develop diagnostics to separate fluctuations from an evolving background. It is found that the fluctuation amplitude starts to grow only when the linear growth rate is sufficiently high to overcome advection loss and the stretching effect due to the outflow. The linear growth rate continues to rise until the sizes of plasmoids become comparable to the inner layer width of the tearing mode. At this point, the current sheet is disrupted and the instability enters the early nonlinear regime. The growth rate suddenly decreases, but the reconnection rate starts to rise rapidly, indicating that current sheet disruption triggers the onset of fast reconnection. We identify important timescales of the instability development, as well as scalings for the linear growth rate, current sheet width, and dominant wavenumber at disruption. These scalings depend not only on the Lundquist number, but also on the noise amplitude. A phenomenological model that reproduces scalings from simulation results is proposed. The model incorporates the effect of reconnection outflow, which is crucial for yielding a critical Lundquist number Sc below which disruption does not occur. The critical Lundquist number Sc is not a constant value, but has a weak dependence on the noise amplitude.
Myeloid derived suppressor cells (MDSC) are important regulators of immune responses. We evaluated the mechanistic role of MDSC depletion on antigen presenting cell (APC), NK, T cell activities and ...therapeutic vaccination responses in murine models of lung cancer.
Individual antibody mediated depletion of MDSC (anti-Gr1 or anti-Ly6G) enhanced the antitumor activity against lung cancer. In comparison to controls, MDSC depletion enhanced the APC activity and increased the frequency and activity of the NK and T cell effectors in the tumor. Compared to controls, the anti-Gr1 or anti-Ly6G treatment led to increased: (i) CD8 T cells, (ii) NK cells, (iii) CD8 T or NK intracytoplasmic expression of IFNγ, perforin and granzyme (iv) CD3 T cells expressing the activation marker CD107a and CXCR3, (v) reduced CD8 T cell IL-10 production in the tumors (vi) reduced tumor angiogenic (VEGF, CXCL2, CXCL5, and Angiopoietin1&2) but enhanced anti-angiogenic (CXCL9 and CXCL10) expression and (vii) reduced tumor staining of endothelial marker Meca 32. Immunocytochemistry of tumor sections showed reduced Gr1 expressing cells with increased CD3 T cell infiltrates in the anti-Gr1 or anti-Ly6G groups. MDSC depletion led to a marked inhibition in tumor growth, enhanced tumor cell apoptosis and reduced migration of the tumors from the primary site to the lung compared to controls. Therapeutic vaccination responses were enhanced in vivo following MDSC depletion with 50% of treated mice completely eradicating established tumors. Treated mice that rejected their primary tumors acquired immunological memory against a secondary tumor challenge. The remaining 50% of mice in this group had 20 fold reductions in tumor burden compared to controls.
Our data demonstrate that targeting MDSC can improve antitumor immune responses suggesting a broad applicability of combined immune based approaches against cancer. This multifaceted approach may prove useful against tumors where MDSC play a role in tumor immune evasion.
We sought to investigate epidemiologic features of Kawasaki disease (KD) in Shanghai from 2013 through 2017 and identify risk factors for coronary artery lesions (CAL).
As in our previous three ...surveys, a set of questionnaires and diagnostic guidelines for KD were sent to 50 hospitals providing pediatric medical care in Shanghai. Medical records of KD patients diagnosed from January 2013 through December 2017 were retrospectively analyzed. Multivariate logistic regression analysis was performed to identify risk factors for CAL.
A total of 4,452 cases were enrolled. Male-to-female ratio was 1.7:1. The incidence of KD was 68.8 to 107.3 per 100,000 children aged <5 years from 2013 to 2017. Age at onset ranged from 15 days to 14.0 years (median: 1.8 years). KD occurred more frequently in spring and summer. Of 4,325 patients (97.0%) receiving intravenous immunoglobulin (IVIG), 362 (8.4%) were resistant to initial IVIG. CAL occurred in 406 (9.1%) patients, including 118 (2.7%) with medium aneurysms and 31 (0.7%) with giant aneurysms. Recurrent cases were 60 (1.3%). No death was found in this survey. Higher platelet levels, lower albumin levels, male sex, incomplete KD, IVIG resistance, and receiving initial IVIG ≤4 days or >10 days, were independently associated with CAL.
The incidence of KD in Shanghai had substantially increased while the proportion of CAL had substantially decreased as compared with our previous surveys. Higher platelet levels, lower albumin levels, male sex, incomplete KD, IVIG resistance, and receiving initial IVIG ≤4 days or >10 days, were risk factors for CAL.
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