Multi-omics integration reveals molecular networks and regulators of psoriasis.

BackgroundPsoriasis is a complex multi-factorial disease, involving both genetic susceptibilities and environmental triggers. Genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) have been carried out to identify genetic and epigenetic variants that are associated with psoriasis. However, these loci cannot fully explain the disease pathogenesis.MethodsTo achieve a comprehensive mechanistic understanding of psoriasis, we conducted a systems biology study, integrating multi-omics datasets including GWAS, EWAS, tissue-specific transcriptome, expression quantitative trait loci (eQTLs), gene networks, and biological pathways to identify the key genes, processes, and networks that are genetically and epigenetically associated with psoriasis risk.ResultsThis integrative genomics study identified both well-characterized (e.g., the IL17 pathway in both GWAS and EWAS) and novel biological processes (e.g., the branched chain amino acid catabolism process in GWAS and the platelet and coagulation pathway in EWAS) involved in psoriasis. Finally, by utilizing tissue-specific gene regulatory networks, we unraveled the interactions among the psoriasis-associated genes and pathways in a tissue-specific manner and detected potential key regulatory genes in the psoriasis networks.ConclusionsThe integration and convergence of multi-omics signals provide deeper and comprehensive insights into the biological mechanisms associated with psoriasis susceptibility

Robust Inference for the Stepped Wedge Design

Based on a permutation argument, we derive a closed form expression for an estimate of the treatment effect, along with its standard error, in a stepped wedge design. We show that these estimates are robust to misspecification of both the mean and covariance structure of the underlying data-generating mechanism, thereby providing a robust approach to inference for the treatment effect in stepped wedge designs. We use simulations to evaluate the type I error and power of the proposed estimate and to compare the performance of the proposed estimate to the optimal estimate when the correct model specification is known. The limitations, possible extensions, and open problems regarding the method are discussed

Electron dynamics in topological insulator based semiconductor-metal interfaces (topological p-n interface based on Bi2Se3 class)

Single-Dirac-cone topological insulators (TI) are the first experimentally discovered class of three dimensional topologically ordered electronic systems, and feature robust, massless spin-helical conducting surface states that appear at any interface between a topological insulator and normal matter that lacks the topological insulator ordering. This topologically defined surface environment has been theoretically identified as a promising platform for observing a wide range of new physical phenomena, and possesses ideal properties for advanced electronics such as spin-polarized conductivity and suppressed scattering. A key missing step in enabling these applications is to understand how topologically ordered electrons respond to the interfaces and surface structures that constitute a device. Here we explore this question by using the surface deposition of cathode (Cu/In/Fe) and anode materials (NO$_2$) and control of bulk doping in Bi$_2$Se$_3$ from P-type to N-type charge transport regimes to generate a range of topological insulator interface scenarios that are fundamental to device development. The interplay of conventional semiconductor junction physics and three dimensional topological electronic order is observed to generate novel junction behaviors that go beyond the doped-insulator paradigm of conventional semiconductor devices and greatly alter the known spin-orbit interface phenomenon of Rashba splitting. Our measurements for the first time reveal new classes of diode-like configurations that can create a gap in the interface electron density near a topological Dirac point and systematically modify the topological surface state Dirac velocity, allowing far reaching control of spin-textured helical Dirac electrons inside the interface and creating advantages for TI superconductors as a Majorana fermion platform over spin-orbit semiconductors.Comment: 14 pages, 4 Figure

Identification of the chemical components of ethanol extract of Chenopodium ambrosioides and evaluation of their in vitro antioxidant and anti tumor activities

Purpose: To determine the characteristic chemical components of the ethanol extract of Chenopodium ambrosioides and evaluate their antioxidant and anti-tumor effects in vitro. Methods: The plant powder (5 g) was extracted with 1 L of 80 % ethanol at room temperature for 45 min, and then placed at 60 oC at varying microwave power and duration to obtain optimal extraction conditions. Characteristic chemical components were detected using ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS/MS). Kaempferitrin was isolated from the 80 % ethanol extract using a D101 macroporous resin column, and its content was assessed by high performance liquid chromatography (HPLC). The antioxidant effect of kaempferitrin was evaluated by its ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radicals, while its anti-proliferation activity in human liver cancer cells SMMC-7721 was determined using cell counting kit-8 (CCK-8) reagent. Results: Three characteristic components of ethanol extract of C. ambrosioides were obtained, namely, kaempferitrin, kaempferol-3-O-apigenin-7-O-rhamnoside and kaempferol-3-O-acetylapigenin-7-O-rhamnoside. Kaempferitrin was shown to possess strong DPPH radical and moderate ABTS radical scavenging activities. Kaempferitrin significantly inhibited the proliferation of SMMC-7721 cells at doses of 4 and 8 μg/mL, with half-maximal concentration (IC50) of 0.38 μM (p < 0.05). Conclusion: Kaempferitrin extracted from C. ambrosioides has antioxidant and anti-tumor activities. The results reported here indicate that C. ambrosioides may have potential use in herbal medicine practice

A high-Q metasurface signal isolator for 1.5T surface coil magnetic resonance imaging on the go

The combination of surface coils and metamaterials remarkably enhance magnetic resonance imaging (MRI) performance for significant local staging flexibility. However, due to the coupling in between, impeded signal-to-noise ratio (SNR) and low-contrast resolution, further hamper the future growth in clinical MRI. In this paper, we propose a high-Q metasurface decoupling isolator fueled by topological LC loops for 1.5T surface coil MRI system, increasing the magnetic field up to fivefold at 63.8 MHz. We have employed a polarization conversion mechanism to effectively eliminate the coupling between the MRI metamaterial and the radio frequency (RF) surface transmitter-receiver coils. Furthermore, a high-Q metasurface isolator was achieved by taking advantage of bound states in the continuum (BIC) for extremely high-field MRI and spectroscopy. An equivalent physical model of the miniaturized metasurface design was put forward through LC circuit analysis. This study opens up a promising route for the easy-to-use and portable surface coil MRI scanners

High sensitivity micro-fiber Mach-Zehnder interferometric temperature sensors with a high index ring layer

The influence of the high index ring layer (HIRL) in a tapered fiber Mach-Zehnder interferometer (MZI) on the interference observed, and thus on its potential applications in temperature sensing, has been investigated. The MZI was comprised of a tapered Ring Core Fiber (RCF), spliced between two single mode fibers (SMF). Since part of core mode from the SMF was converted into cladding modes in the RCF, due to the mismatch in the cores between the RCF and SMF, the residual power enters and then propagates along the center of the RCF (silica). The difference in phase between the radiation travelling along these different paths is separated by the HIRL to generate an interference effect. Compared with fiber interferometers based on core and cladding mode interference, the thin fiber HIRL is capable of separating the high order cladding modes and the silica core mode, under grazing incident conditions. Therefore, the optical path difference (OPD) and the sensitivity are both substantially improved over what is seen in conventional devices, showing their potential for interferometric temperature sensor applications. The optimum temperature sensitivity obtained was 186.6 pm/°C, which is ∼ 11.7 times higher than has been reported previously