Hepatitis B antibody levels after different doses of hepatitis B vaccination: a retrospective study based on hospitalized children.

Many studies have investigated the positivity rate of hepatitis B surface antibody (HBsAb) after hepatitis B vaccine (HepB) immunization. However, the antibody level, assessed monthly or at more frequent intervals after each of the three doses, particularly within the first year after birth, has not been previously reported. To elucidate the level of antibody formation at various times after vaccination, the current study used the available detection data of HBsAb in hospitalized children to analyze the HBsAb level after immunization combined with their vaccination history. Both the positivity rate and geometric mean concentration (GMC) increased sequentially with immunization doses, reaching their peaks earlier after the third dose than after the first two doses, and the rate of HBsAb positivity was able to reach 100% between 11 and 90 days after completing the three doses of HepB. Within one year after receiving the three doses, the antibody positivity rate and GMC were maintained above 90% and 100 mIU/mL, respectively, and subsequently steadily declined, reaching the lowest value in the 9th and 10th years. The current findings reveal, in more detail, the level of antibody formation at different times following each dose of HepB in hospitalized children, particularly in the age group up to one year after vaccination. For the subjects of this study, we prefer to believe that the proportion of HBsAb non-response should be less than 5% after full immunization with HepB, provided that the appropriate time for blood collection is chosen.

Variable self-powered light detection CMOS chip with real-time adaptive tracking digital output based on a novel on-chip sensor.

This paper provides a solution for a self-powered light direction detection with digitized output. Light direction sensors, energy harvesting photodiodes, real-time adaptive tracking digital output unit and other necessary circuits are integrated on a single chip based on a standard 0.18 µm CMOS process. Light direction sensors proposed have an accuracy of 1.8 degree over a 120 degree range. In order to improve the accuracy, a compensation circuit is presented for photodiodes' forward currents. The actual measurement precision of output is approximately 7 ENOB. Besides that, an adaptive under voltage protection circuit is designed for variable supply power which may undulate with temperature and process.

Active tracking system for visible light communication using a GaN-based micro-LED and NRZ-OOK.

Visible light communication (VLC) holds the promise of a high-speed wireless network for indoor applications and competes with 5G radio frequency (RF) system. Although the breakthrough of gallium nitride (GaN) based micro-light-emitting-diodes (micro-LEDs) increases the -3dB modulation bandwidth exceptionally from tens of MHz to hundreds of MHz, the light collected onto a fast photo receiver drops dramatically, which determines the signal to noise ratio (SNR) of VLC. To fully implement the practical high data-rate VLC link enabled by a GaN-based micro-LED, it requires focusing optics and a tracking system. In this paper, we demonstrate an active on-chip tracking system for VLC using a GaN-based micro-LED and none-return-to-zero on-off keying (NRZ-OOK). Using this novel technique, the field of view (FOV) was enlarged to 120° and data rates up to 600 Mbps at a bit error rate (BER) of 2.1×10-4 were achieved without manual focusing. This paper demonstrates the establishment of a VLC physical link that shows enhanced communication quality by orders of magnitude, making it optimized for practical communication applications.

Optical properties of highly polarized InGaN light-emitting diodes modified by plasmonic metallic grating.

We implement finite-difference time-domain (FDTD) method to simulate the optical properties of highly polarized InGaN light emitting diodes (LEDs) coupled with metallic grating structure. The Purcell factor (Fp), light extraction efficiency (LEE), internal quantum efficiency (IQE), external quantum efficiency (EQE), and modulation frequency are calculated for different polarized emissions. Our results show that light polarization has a strong impact on Fp and LEE of LEDs due to their coupling effects with the surface plasmons (SPs) generated by metallic grating. Fp as high as 34 and modulation frequency up to 5.4 GHz are obtained for a simulated LED structure. Furthermore, LEE, IQE and EQE can also be enhanced by tuning the coupling between polarized emission and SPs. These results can serve as guidelines for the design and fabrication of high efficiency and high speed LEDs for the applications of solid-state lighting and visible-light communication.

CMOS self-powered monolithic light-direction sensor with digitalized output.

We present a novel self-powered chip to detect the direction of incident light. This chip directly provides digitized output without the need of any off-chip power supply or optical or mechanical components. The chip was implemented in a standard 0.5 µm CMOS process. A microscale metal baffle was created by stacking all metal layers, contacts, and vias available in the process to produce on-chip shadowing. N-well/p+ photodiode arrays are located on both sides of the baffle to sense light. The photocurrent generated by a photodiode depends on the size of the photodiode and the shadowing. The shadowed area depends on the incident angle of the light. A current mirror circuit is used to compare the currents generated by the photodiodes on the opposite sides of the baffle and, consequently, provide a digital signal to indicate the incident light angle. Compared with the ideal linear digital light-angle detector with the same resolution, the presented sensor achieved the maximum error of only 2 deg over 110 deg test range.

Enhanced 5-fluorouracil cytotoxicity in high COX-2 expressing hepatocellular carcinoma cells by wogonin via the PI3K/Akt pathway.

Combination therapies may increase the antitumor effects and reduce the adverse effects for the treatment of hepatocellular carcinoma. In this study, we determined the effects of 5-fluorouracil alone or in combination with wogonin in vitro and in vivo, and we investigated the possible mechanisms. The combination of these 2 drugs led to a decrease in survival and a significant synergistic inhibitory effect on high COX-2 expression in SMMC-7721 hepatocellular carcinoma (HCC) cells. Furthermore, the results show that this combination inhibits COX-2 expression and increases sensitivity to chemotherapeutic agents partly through regulating the PI3K/Akt signaling pathway. Moreover, the combination treatment caused a significant growth inhibition of human tumor xenografts in vivo. In conclusion, wogonin may increase the cytotoxicity of some antineoplastic agents and it can be used in combination with these agents as a novel therapeutic regimen for HCC treatment.

Multi-channel current electro-optic isolated measurement and discharge current characteristics in a parallel plate transmission line driver.

In this paper, a 96 kJ compact synchronous discharge driver is designed. The issue of the current measurement of the six parallel gas spark switches is resolved by a multi-channel isolated current measuring system, and the driver's circuit simulation model is constructed. Then, the discharge current characteristics of each branch and load are investigated, and the results show that when the operating voltage is at least 50 kV, the parallel switches are conducted synchronously. The designed multi-channel isolated current measuring system meets the use requirements at a maximum operating voltage of 80 kV, the peak current measured by a single channel is 500 kA at this time, which corresponds to the load current of 3 MA, and the current rise time (0%-100% rise time) is about 1.15 µs. However, the asynchronous conduction of these switches will increase the branch circuit's peak current by a maximum of 25%, and the maximum value of the inverse peak current ratio of the branch will increase to 1.16, which will threaten the safe operation of the components. At this time, there is a redistribution of charge between the already conducting branches, so the impact of the load current is less than that of the basic branch current. When the conduction dispersion of the switchers is less than 452 ns, the peak current of the load reduction is less than 3%, and the current waveform meets the application requirements. The research is essential for understanding the operating status of the driver and assessing the through-current capability of the device's components, such as gas switches and capacitors.

VI-14, a novel flavonoid derivative, inhibits migration and invasion of human breast cancer cells.

It has been well characterized that flavonoids possess pronounced anticancer potentials including anti-angiogenesis, anti-metastasis, and pro-apoptosis. Herein, we report, for the first time, that VI-14, a novel flavonoid derivative, possesses anti-cancer properties. The purpose of this study is to investigate the anti-migration and anti-invasion activities of VI-14 in breast cancer cells. Our data indicate that VI-14 inhibits adhesion, migration and invasion of MDA-MB-231 and MDA-MB-435 human breast cancer cells. MDA-MB-231 cells treated with VI-14 display reduced activities and expressions of ECM degradation-associated proteins including matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) at both the protein and mRNA levels. Meanwhile, VI-14 treatment induces an up-regulated expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and 2 (TIMP-2) in MDA-MB-231 cells. Western blotting results show that phosphorylation levels of critical components of the MAPK signaling pathway, including ERK, JNK and P38, are dramatically decreased in VI-14-treated MDA-MB-231 cells. Furthermore, treatment of VI-14 significantly decreases the nuclear levels and the binding ability of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). Taken together, our data suggest that VI-14 treatment suppresses migration and motility of breast cancer cells, and VI-14 may be a potential compound for cancer therapy.

SAR studies on the central phenyl ring of substituted biphenyl oxazolidinone-potent CETP inhibitors.

SAR studies of the substitution effect on the central phenyl ring of the biphenyl scaffold were carried out using anacetrapib (9a) as the benchmark. The results revealed that the new analogs with substitutions to replace trifluoromethyl (9a) had a significant impact on CETP inhibition in vitro. In fact, analogs with some small groups were as potent or more potent than the CF(3) derivative for CETP inhibition. Five of these new analogs raised HDL-C significantly (>20mg/dL). None of them however was better than anacetrapib in vivo. The synthesis and biological evaluation of these CETP inhibitors are described.

Development of a repetitive plasma source for simulation of mitigated edge localized mode transient heat load.

A repetitive plasma source for simulation of mitigated edge localized mode transient heat load is developed. The repetitive plasma source consists of a repetitive pulsed power supply and a pulsed plasma accelerator. The pulsed plasma accelerator is composed of a coaxial cathode, an anode, and an insulator. The inner electrode is the cathode with a diameter of 5 mm, and the outer electrode is the anode with a diameter of 15 mm. An angular magnetic field is generated by the discharge current and acts with the radial current to generate Lorentz force, which drives the plasma ejecting to the outlet. The repetitive pulsed power supply can be divided into three parts, the primary charge circuit, the resonant charge circuit, and the discharge circuit. The time interval between resonant charge and discharge is 4 ms. The repetitive discharge components include ten modules running in parallel. There are four working modes for discharge components, depending on the number of simultaneously discharged modules. For Mode A, the maximum repetitive frequency is 50 Hz, and the transient heat load is 0.06 MJ/m2 when the discharge current is 10.5 kA. For Mode D, the maximum repetitive frequency is 5 Hz, and the transient heat load is 0.45 MJ/m2 when the discharge current is 66 kA. This is of great significance for the study of the interaction between plasma and plasma-facing materials in tokamak.

Oxidation and ordering of fine structure of corn starch under an ultrahigh magnetic field.

In this study, corn starch (40 % moisture content) was placed in an ultra-high magnetic field(UMF)(5-20 T) to investigate the ordering and stabilization process under the magnetic field. With the increase of the intensity of UMF, C-OH and O-C-O were oxidized to O = C-OH and cross-linked to form ester bonds. When the UMF intensity was 15 T, the effect was the most significant with the ordered short-range structures formed; since the O = C-OR enhanced carbon skeleton structure, the crystallinity increased comparatively and amylose content reached the minimum value (15.32 ± 0.04 %). Additionally, UMF has a compressive effect on the void structure of A-type starch, and the average particle size decreased. RVA and DSC demonstrated that the UMF-treated starch had better thermal stability and shear resistance. This study suggested that UMF could serve as a prospective technique for starch product processing.

Dielectric Surface Flashover under Long-Term Repetitive Microsecond Pulses in Compressed Gas Environment.

As a key component of a high-power microwave (HPM) system, a multi-gap gas switch (MGS) has recently developed insulation failure due to surface flashover. Although design criteria for surface insulation have been put forward, it is still not clear how the insulation in this case deteriorated under long-term repetitive microsecond pulses (RMPs). In this paper, flashover experiments under RMPs were carried out on various dielectric surfaces between parallel-plane electrodes in SF6 and air atmospheres, respectively. Based on tests of the surface insulation lifetime (SIL), an empirical formula for SIL prediction is proposed with variations of insulator work coefficient λ, which is a more suitable parameter to characterize SIL under RMPs. Due of the accumulation effect, the relationship between E/p and ptdelay varies with the pulse repetitive frequency (PRF) and SIL recovery capability decreases with an increase in PRF and surface deterioration is exacerbated during successive flashovers. It is concluded that the flashover path plays a crucial role in surface insulation performance under RMPs due to the photoemission induced by ultraviolet (UV) radiation, signifying the necessity of reducing surface paths in future designs as well as the improvement of surface insulation.

Invention of MK-8262, a Cholesteryl Ester Transfer Protein (CETP) Inhibitor Backup to Anacetrapib with Best-in-Class Properties.

Cholesteryl ester transfer protein (CETP) represents one of the key regulators of the homeostasis of lipid particles, including high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles. Epidemiological evidence correlates increased HDL and decreased LDL to coronary heart disease (CHD) risk reduction. This relationship is consistent with a clinical outcomes trial of a CETP inhibitor (anacetrapib) combined with standard of care (statin), which led to a 9% additional risk reduction compared to standard of care alone. We discuss here the discovery of MK-8262, a CETP inhibitor with the potential for being the best-in-class molecule. Novel in vitro and in vivo paradigms were integrated to drug discovery to guide optimization informed by a critical understanding of key clinical adverse effect profiles. We present preclinical and clinical evidence of MK-8262 safety and efficacy by means of HDL increase and LDL reduction as biomarkers for reduced CHD risk.

Design of a novel class of biphenyl CETP inhibitors.

A new class of CETP inhibitors was designed and prepared. These compounds are potent both in vitro and in vivo. The most active compound (12d) has shown an ability to raise HDL significantly in transgenic mouse PD model.

From Screening to Targeted Degradation: Strategies for the Discovery and Optimization of Small Molecule Ligands for PCSK9.

Proprotein convertase substilisin-like/kexin type 9 (PCSK9) is a serine protease involved in a protein-protein interaction with the low-density lipoprotein (LDL) receptor that has both human genetic and clinical validation. Blocking this protein-protein interaction prevents LDL receptor degradation and thereby decreases LDL cholesterol levels. Our pursuit of small-molecule direct binders for this difficult to drug PPI target utilized affinity selection/mass spectrometry, which identified one confirmed hit compound. An X-ray crystal structure revealed that this compound was binding in an unprecedented allosteric pocket located between the catalytic and C-terminal domain. Optimization of this initial hit, using two distinct strategies, led to compounds with high binding affinity to PCSK9. Direct target engagement was demonstrated in the cell lysate with a cellular thermal shift assay. Finally, ligand-induced protein degradation was shown with a proteasome recruiting tag attached to the high-affinity allosteric ligand for PCSK9.

Regulation of GDF-8 signaling by the p38 MAPK.

Growth differentiation factor-8 (GDF-8), a member of the TGF-beta superfamily, is a negative regulator of skeletal muscle growth, which functions through activation of the Smad proteins. We found that GDF-8 can activate the p38 mitogen-activated protein kinase (MAPK) through the TGF-beta-activated kinase 1 (TAK1), and this appeared to be independent of Smad signaling. GDF-8-induced transcriptional activation was inhibited by expression of dominant negative MKK6 or treatment with the p38 inhibitor SB203580, while overexpression of wild-type forms of either MKK6 or p38 augmented GDF-8-induced transcriptional activity. In addition, ATF-2, a known transcription factor target of p38, was found to be phosphorylated on GDF-8 stimulation and was detected in a complex with Smad3/Smad4 upon GDF-8 treatment. Furthermore, we found that the p38 MAPK played an important role in GDF-8-induced inhibition of proliferation and upregulation of the cyclin kinase inhibitor p21. Together, these results highlight a functional link between the p38 MAPK and GDF-8-activated Smad pathways, and identify a critical role for the p38 MAPK in GDF-8's function as a negative regulator of muscle growth.

Modeling aided design of potent glycogen phosphorylase inhibitors.

Molecular modeling has been used to assist in the development of a novel series of potent glycogen phosphorylase inhibitors based on a phenyl diacid lead, compound 1. In the absence of suitable competitive binding assays, compound 1 was predicted to bind at the AMP allosteric site based on superposition onto known inhibitors which bind at different sites in the enzyme and analyses of the surrounding protein environment associated with these distinct sites. Possible docking modes of compound 1 at the AMP allosteric site were further explored using the crystal structure of rabbit muscle glycogen phosphorylase complexed with a Bayer diacid compound W1807 (PDB entry 3AMV). Compound 1 was predicted to interact with positively charged arginines at the AMP allosteric site in the docking model. Characterization of the binding pocket by a grid-based surface calculation of the docking model revealed a large unfilled hydrophobic region near the central phenyl ring, suggesting that compounds with larger hydrophobic groups in this region would improve binding. A series of naphthyl diacid compounds were designed and synthesized to access this hydrophobic cleft, and showed significantly improved potency.

A self-powered 2-dimensional motion detection chip.

We demonstrate a self-powered chip to detect motion which enables constant, non-invasive monitoring. The chip was implemented in a standard 0.18 µm CMOS process. A P-N junction photodiode array was fabricated in the chip to detect when light is blocked by the movement of a hand or finger. The interface circuit detects the change between the shadowing and the exposure to determine the specific movement. This entire chip operates without any off-chip power supply and provides digitized outputs including 1 bit direction output and an 8 bits output indicative of the velocity in two dimensions.