2.4 GHz Phase Locked Loop with DLL Based Spur Suppression Technique in 40nm CMOS

Phase locked loops (PLLs) are widely used as frequency synthesizers in modern communication systems because of the frequency accuracy and programmability of output frequency. Reference spur is an issue of concern in the PLL design as it merges the interference into the desired signal band. This study focuses on the design of PLLs with low reference spurs level. A PLL with 2.4 GHz output frequency is implemented in TSMC 40nm CMOS technology using a 1.1V supply. A delay locked loop (DLL) is inserted in the phase locked loop as a multiple phase generator, in order to move the fundamental spur to higher frequency. The influence of errors inside the DLL due to CMOS process on the performance of spur suppression is also analyzed in this work. Two independent calibration systems, continuous time calibration and switch capacitor integrator based calibration for DLL’s errors are presented, to reduce the delay errors. A spur reduction of 35 dB compared to a conventional structure is verified by the schematic simulation in Cadence

Identification of novel urine proteomic biomarkers for high stamina in high-altitude adaptation

Introduction: We aimed to identify urine biomarkers for screening individuals with adaptability to high-altitude hypoxia with high stamina levels. Although most non-high-altitude natives experience rapid decline in physical ability when ascending to high altitudes, some individuals with high-altitude adaptability continue to maintain high endurance levels.Methods: We divided the study population into two groups: the LC group (low change in endurance from low to high altitude) and HC group (high change in endurance from low to high altitude). We performed blood biochemistry testing for individuals at high altitudes and sea level. We used urine peptidome profiling to compare the HH (high-altitude with high stamina) and HL (high-altitude with low stamina) groups and the LC and HC groups to identify urine biomarkers.Results: Routine blood tests revealed that the concentration of white blood cells, lymphocytes and platelets were significantly higher in the HH group than in the HL group. Urine peptidome profiling showed that the proteins ITIH1, PDCD1LG2, NME1-NME2, and CSPG4 were significantly differentially expressed between the HH and HL groups, which was tested using ELISA. Urine proteomic analysis showed that LRG1, NID1, VASN, GPX3, ACP2, and PRSS8 were urine proteomic biomarkers of high stamina during high-altitude adaptation.Conclusion: This study provides a novel approach for identifying potential biomarkers for screening individuals who can adapt to high altitudes with high stamina

Ultra-short lifetime isomer studies from photonuclear reactions using laser-driven ultra-intense {\gamma}-ray

Isomers, ubiquitous populations of relatively long-lived nuclear excited states, play a crucial role in nuclear physics. However, isomers with half-life times of several seconds or less barely had experimental cross section data due to the lack of a suitable measuring method. We report a method of online {\gamma} spectroscopy for ultra-short-lived isomers from photonuclear reactions using laser-driven ultra-intense {\gamma}-rays. The fastest time resolution can reach sub-ps level with {\gamma}-ray intensities >10^{19}/s ({\geqslant} 8 MeV). The ^{115}In({\gamma}, n)^{114m2}In reaction (T_{1/2} = 43.1 ms) was first measured in the high-energy region which shed light on the nuclear structure studies of In element. Simulations showed it would be an efficient way to study ^{229m}Th (T_{1/2} = 7 {\mu}s), which is believed to be the next generation of nuclear clock. This work offered a unique way of gaining insight into ultra-short lifetimes and promised an effective way to fill the gap in relevant experimental data

Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: A randomised, double-blind, placebo-controlled trial

Objectives Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebocontrolled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy. Methods A randomised, double-blind and placebocontrolled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets. Results At week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells. Conclusions Low-dose IL-2 might be effective and tolerated in treatment of SThe work was supported by the National Natural Science Foundation of China (31530020,31570880,81471601,81601417 and 81701598), Peking-Tsinghua Center for Life Sciences to ZG LI, Beijing Sci-Tech Committee Z171100000417007,Clinical Medicine Plus X-Young Scholars Project of Peking University (PKU2019LCXQ013) supported by the Fundamental Research Funds for the Central Universities, Beijing Nova Program Z171100001117025, National Key Research and Development Program of China (2017YFC0909003 to DY), BellberryViertel Senior Medical Research Fellowship to DY and Beijing SL PHARM

Fasting induces a high level of 3-nitrotyrosine in the brain of rats

Although the relationship between hyperglycemia (using diabetic animal model) and plasma nitrotyrosine level has been studied, the effect of hypoglycemia on nitrotyrosine level in the brain has not been addressed. Here, we evaluated nitration of protein, the colocalization of nitration with alpha-synuclein, activity of inducible nitric oxide synthase, and nitric oxide content using fasting and diabetic animal models. The results showed that signals of alpha-synuclein were widely distributed in most parts of the pallium, midbrain, hippocampus and cerebellum, as indicated by immunohistochemistry. Most signals of the 3-nitrotyrosine were colocalized with those of alpha-synuclein in the midbrain of fasting rats. The level of proteins containing 3-nitrotyrosine was significantly increased in the brain of fasting rats in Western blotting, especially in the midbrain, compared with control rats. In addition, the 3-nitrotyrosine signals increased in hippocampus of diabetic rats. Immunoprecipitation showed that alpha-synuclein was nitrated in the fasting rats. The iNOS activity and nitric oxide levels were significantly increased in both fasting and diabetic animals. The enhanced 3-nitrotyrosine level in the brain of fasting rats suggests that nitration of protein including alpha-synuclein in the midbrain is more affected by hypoglycemia in fasting than hyperglycemia in diabetic rats. (C) 2010 Elsevier Ireland Ltd. All rights reserved

Two-dimensional Simulation of Motion of Red Blood Cells with Deterministic Lateral Displacement Devices

Deterministic lateral displacement (DLD) technology has great potential for the separation, enrichment, and sorting of red blood cells (RBCs). This paper presents a numerical simulation of the motion of RBCs using DLD devices with different pillar shapes and gap configurations. We studied the effect of the pillar shape, row shift, and pillar diameter on the performance of RBC separation. The numerical results show that the RBCs enter “displacement mode” under conditions of low row-shift (∆λ < 1.4 µm) and “zigzag mode” with large row shift (∆λ > 1.5 µm). RBCs can pass the pillar array when the size of the pillar (d > 6 µm) is larger than the cell size. We show that these conclusions can be helpful for the design of a reliable DLD microfluidic device for the separation of RBCs