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Aim： To explore the potent inhibitor from one of the Traditional Chinese medicine （TCM）, Epimedium sagittatum. Methods： We predicted the potent compound, ESO3b, de novo evolution from the four Epimedium sagittatum components were verified by molecular docking, pharmacophore analysis, and analysis of quantitative structure-activity relationship （QSAR） model, which was constructed by multiple linear regression. Results： ESO3b was chosen to undergo drug modification via de novo evolution. By analyzing the pharmacophore features, we found that the hydrophobic core in the binding site and the hydrogen bond generated at Asn663 played key roles in designing PDE5 inhibitors. ESO3b generated 49 diversities （Evo01-49）. Evo48 had high activity in prediction. Although the value of prediction was overestimated, Evo48 was suggested as the potent lead. Conclusion： In this study, we showed that the hydrophobic core in the binding site and hydrogen bond production on Asn663 played key roles to design PDE5 inhibitors. From several require validation analysis, Evo48 was suggested to be a potent inhibitor.

We describe the Fourier Transform Spectrometer (FTS) used for in-field testing of the POLARBEAR receiver, an experiment located in the Atacama Desert of Chile which measures the cosmic microwave background (CMB) polarization. The POLARBEAR-FTS (PB-FTS) is a Martin-Puplett interferometer designed to couple to the Huan Tran Telescope (HTT) on which the POLARBEAR receiver is installed. The PB-FTS measured the spectral response of the POLARBEAR receiver with signal-to-noise ratio (SNR) \\(>20\\) for \\(\\)69% of the focal plane detectors due to three features: a high throughput of 15.1 steradian cm\\(^2\\), optimized optical coupling to the POLARBEAR optics using a custom designed output parabolic mirror, and a continuously modulated output polarizer. The PB-FTS parabolic mirror is designed to mimic the shape of the 2.5 m-diameter HTT primary reflector which allows for optimum optical coupling to the POLARBEAR receiver, reducing aberrations and systematics. One polarizing grid is placed at the output of the PB-FTS, and modulated via continuous rotation. This modulation allows for decomposition of the signal into different harmonics that can be used to probe potentially pernicious sources of systematic error in a polarization-sensitive instrument. The high throughput and continuous output polarizer modulation features are unique compared to other FTS calibrators used in the CMB field. In-field characterization of the POLARBEAR receiver was accomplished using the PB-FTS in April 2014. We discuss the design, construction, and operation of the PB-FTS and present the spectral characterization of the POLARBEAR receiver. We introduce future applications for the PB-FTS in the next-generation CMB experiment, the Simons Array.

New experiments that target the B-mode polarization signals in the Cosmic Microwave Background require more sensitivity, more detectors, and thus larger-aperture millimeter-wavelength telescopes, than previous experiments. These larger apertures require ever larger vacuum windows to house cryogenic optics. Scaling up conventional vacuum windows, such as those made of High Density Polyethylene (HDPE), require a corresponding increase in the thickness of the window material to handle the extra force from the atmospheric pressure. Thicker windows cause more transmission loss at ambient temperatures, increasing optical loading and decreasing sensitivity. We have developed the use of woven High Modulus Polyethylene (HMPE), a material 100 times stronger than HDPE, to manufacture stronger, thinner windows using a pressurized hot lamination process. We discuss the development of a specialty autoclave for generating thin laminate vacuum windows and the optical and mechanical characterization of full scale science grade windows, with the goal of developing a new window suitable for BICEP Array cryostats and for future CMB applications.

We present a measurement of the gravitational lensing deflection power spectrum reconstructed with two seasons cosmic microwave background polarization data from the POLARBEAR experiment. Observations were taken at 150 GHz from 2012 to 2014 which survey three patches of sky totaling 30 square degrees. We test the consistency of the lensing spectrum with a Cold Dark Matter (CDM) cosmology and reject the no-lensing hypothesis at a confidence of 10.9 sigma including statistical and systematic uncertainties. We observe a value of A_L = 1.33 +/- 0.32 (statistical) +/- 0.02 (systematic) +/- 0.07 (foreground) using all polarization lensing estimators, which corresponds to a 24% accurate measurement of the lensing amplitude. Compared to the analysis of the first year data, we have improved the breadth of both the suite of null tests and the error terms included in the estimation of systematic contamination.

The polarization of the atmosphere has been a long-standing concern for ground-based experiments targeting cosmic microwave background (CMB) polarization. Ice crystals in upper tropospheric clouds scatter thermal radiation from the ground and produce a horizontally-polarized signal. We report the detailed analysis of the cloud signal using a ground-based CMB experiment, POLARBEAR, located at the Atacama desert in Chile and observing at 150 GHz. We observe horizontally-polarized temporal increases of low-frequency fluctuations (\"polarized bursts,\" hereafter) of \\(\\)0.1 K when clouds appear in a webcam monitoring the telescope and the sky. The hypothesis of no correlation between polarized bursts and clouds is rejected with \\(>\\)24\\(\\) statistical significance using three years of data. We consider many other possibilities including instrumental and environmental effects, and find no other reasons other than clouds that can explain the data better. We also discuss the impact of the cloud polarization on future ground-based CMB polarization experiments.

The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands: 27, 39, 93, 145, 225 and 280 GHz. The initial configuration of SO will have three small-aperture 0.5-m telescopes (SATs) and one large-aperture 6-m telescope (LAT), with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The SATs will target the largest angular scales observable from Chile, mapping ~10% of the sky to a white noise level of 2 \\(\\)K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, \\(r\\), at a target level of \\((r)=0.003\\). The LAT will map ~40% of the sky at arcminute angular resolution to an expected white noise level of 6 \\(\\)K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the LSST sky region and partially with DESI. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.

The POLARBEAR-2/Simons Array Cosmic Microwave Background (CMB) polarization experiment is an upgrade and expansion of the existing POLARBEAR-1 (PB-1) experiment, located in the Atacama desert in Chile. Along with the CMB temperature and \\(E\\)-mode polarization anisotropies, PB-1 and the Simons Array study the CMB \\(B\\)-mode polarization anisotropies produced at large angular scales by inflationary gravitational waves, and at small angular scales by gravitational lensing. These measurements provide constraints on various cosmological and particle physics parameters, such as the tensor-to-scalar ratio \\(r\\), and the sum of the neutrino masses. The Simons Array consists of three 3.5 m diameter telescopes with upgraded POLARBEAR-2 (PB-2) cryogenic receivers, named PB-2a, -2b, and -2c. PB-2a and -2b will observe the CMB over multiple bands centered at 95 GHz and 150 GHz, while PB-2c will observe at 220 GHz and 270 GHz, which will enable enhanced foreground separation and de-lensing. Each Simons Array receiver consists of two cryostats which share the same vacuum space: an optics tube containing the cold reimaging lenses and Lyot stop, infrared-blocking filters, and cryogenic half-wave plate; and a backend which contains the focal plane detector array, cold readout components, and millikelvin refrigerator. Each PB-2 focal plane array is comprised of 7,588 dual-polarization, multi-chroic, lenslet- and antenna-coupled, Transition Edge Sensor (TES) bolometers which are cooled to 250 mK and read out using Superconducting Quantum Interference Devices (SQUIDs) through a digital frequency division multiplexing scheme with a multiplexing factor of 40. In this work we describe progress towards commissioning the PB-2b and -2c receivers including cryogenic design, characterization, and performance of both the PB-2b and -2c backend cryostats.

The Simons Observatory (SO) is a ground-based cosmic microwave background (CMB) experiment sited on Cerro Toco in the Atacama Desert in Chile that promises to provide breakthrough discoveries in fundamental physics, cosmology, and astrophysics. Supported by the Simons Foundation, the Heising-Simons Foundation, and with contributions from collaborating institutions, SO will see first light in 2021 and start a five year survey in 2022. SO has 287 collaborators from 12 countries and 53 institutions, including 85 students and 90 postdocs. The SO experiment in its currently funded form ('SO-Nominal') consists of three 0.4 m Small Aperture Telescopes (SATs) and one 6 m Large Aperture Telescope (LAT). Optimized for minimizing systematic errors in polarization measurements at large angular scales, the SATs will perform a deep, degree-scale survey of 10% of the sky to search for the signature of primordial gravitational waves. The LAT will survey 40% of the sky with arc-minute resolution. These observations will measure (or limit) the sum of neutrino masses, search for light relics, measure the early behavior of Dark Energy, and refine our understanding of the intergalactic medium, clusters and the role of feedback in galaxy formation. With up to ten times the sensitivity and five times the angular resolution of the Planck satellite, and roughly an order of magnitude increase in mapping speed over currently operating (\"Stage 3\") experiments, SO will measure the CMB temperature and polarization fluctuations to exquisite precision in six frequency bands from 27 to 280 GHz. SO will rapidly advance CMB science while informing the design of future observatories such as CMB-S4.

Oligodendrocytes myelinate axons in the central nervous system and develop from oligodndrocyte precursor cells (OPCs) that must first migrate extensively during brain and spinal cord development. We show that OPCs require the vasculature as a physical substrate for migration. We observed that OPCs of the embryonic mouse brain and spinal cord, as well as the human cortex, emerge from progenitor domains and associate with the abluminal endothelial surface of nearby blood vessels. Migrating OPCs crawl along and jump between vessels. OPC migration in vivo was disrupted in mice with defective vascular architecture but was normal in mice lacking pericytes. Thus, physical interactions with the vascular endothelium are required for OPC migration. We identify Wnt-Cxcr4 (chemokine receptor 4) signaling in regulation of OPC-endothelial interactions and propose that this signaling coordinates OPC migration with differentiation.

Simultaneous anti- and anti-inflammatory actions are highly beneficial in treating acne vulgaris. In this study, we present novel anti-acne nanovesicles based on liposomes loaded with proteinase K (PK), retinoic acid (RA), and soyaethyl morpholinium ethosulfate (SME) to achieve an effective and safe treatment. This study examined in vitro planktonic and biofilm elimination, as well as the keratinocyte proliferation suppression by liposomes. The multifunctional liposomes for treating in mice were also evaluated. We acquired multifunctional liposomes with a size of 71 nm and zeta potential of 31 mV. The antimicrobial activity of SME was enhanced after liposomal encapsulation according to the reduction of minimum bactericidal concentration (MBC) by 6-fold. The multifunctional liposomes exhibited a synergistically inhibitory effect on biofilm colonization compared with the liposomes containing PK or those containing SME individually. The adhesive bacterial colony in the microplate was lessened by 62% after multifunctional liposome intervention. All liposomal formulations tested here demonstrated no cytotoxicity against the normal keratinocytes but inhibited -stimulated cell hyperproliferation. The in vitro scratch assay indicated that the liposomal RA-but not free RA-restrained keratinocyte migration. The animal study showed that free RA combined with SME and multifunctional nanovesicles had a similar effect on diminishing colonies in the skin. On the other hand, liposomes exhibited superior performance in recovering the impaired skin barrier function than the free control. We also found that RA-loaded nanovesicles had greater skin tolerability than free RA. The cationic liposomes containing dual PK and RA represented a potential treatment to arrest bacterial infection and associated inflammation in acne.