The functional engagement between an enhancer and its target promoter ensures precise gene transcription
. Understanding the basis of promoter choice by enhancers has important implications for ...health and disease. Here we report that functional loss of a preferred promoter can release its partner enhancer to loop to and activate an alternative promoter (or alternative promoters) in the neighbourhood. We refer to this target-switching process as 'enhancer release and retargeting'. Genetic deletion, motif perturbation or mutation, and dCas9-mediated CTCF tethering reveal that promoter choice by an enhancer can be determined by the binding of CTCF at promoters, in a cohesin-dependent manner-consistent with a model of 'enhancer scanning' inside the contact domain. Promoter-associated CTCF shows a lower affinity than that at chromatin domain boundaries and often lacks a preferred motif orientation or a partnering CTCF at the cognate enhancer, suggesting properties distinct from boundary CTCF. Analyses of cancer mutations, data from the GTEx project and risk loci from genome-wide association studies, together with a focused CRISPR interference screen, reveal that enhancer release and retargeting represents an overlooked mechanism that underlies the activation of disease-susceptibility genes, as exemplified by a risk locus for Parkinson's disease (NUCKS1-RAB7L1) and three loci associated with cancer (CLPTM1L-TERT, ZCCHC7-PAX5 and PVT1-MYC).
As part of the research on cement composites using cellulose nanocrystal (CNC) aqueous solution instead of general water, this study produced high-toughness cement composites reinforced with flax and ...steel fibers to improve the tensile deformation capacity, assessing the isothermal conduction calorimetry analysis, drying shrinkage, and strength characteristics. The mixing amount of CNCs was 0.4, 0.8, and 1.2 vol.% by volume of cement, and an aqueous solution was prepared using the ultrasonication dispersion method. When comparing the results of the experiment according to the CNC mixing ratio, CNCs at 0.8 vol.% led to an improvement in the shrinkage rate and mechanical performance compared with the plain specimen.
We present a novel approach for generating targeted deletions of genomic segments in human and other eukaryotic cells using engineered zinc finger nucleases (ZFNs). We found that ZFNs designed to ...target two different sites in a human chromosome could introduce two concurrent DNA double-strand breaks (DSBs) in the chromosome and give rise to targeted deletions of the genomic segment between the two sites. Using this method in human cells, we were able to delete predetermined genomic DNA segments in the range of several-hundred base pairs (bp) to 15 mega-bp at frequencies of 10(-3) to 10(-1). These high frequencies allowed us to isolate clonal populations of cells, in which the target chromosomal segments were deleted, by limiting dilution. Sequence analysis revealed that many of the deletion junctions contained small insertions or deletions and microhomologies, indicative of DNA repair via nonhomologous end-joining. Unlike other genome engineering tools such as recombinases and meganucleases, ZFNs do not require preinsertion of target sites into the genome and allow precise manipulation of endogenous genomic scripts in animal and plant cells. Thus, ZFN-induced genomic deletions should be broadly useful as a novel method in biomedical research, biotechnology, and gene therapy.
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•Exposed areas of graphene multilayers can accelerate serious damage of the coated metal.•Steel surfaces can be protected by reduced graphene oxide (RGO) coatings.•Addition of Iron ...oxide nanoparticles can improve adhesion strength and oxidation resistance of RGO coatings.
Despite its potential for use in coating applications, graphene can promote corrosion at exposed graphene-metal interfaces because it presents cathodic properties when exposed to most metals. Moreover, such exposed areas can accelerate localized corrosion, which may lead to serious damage of the coated metal. This study describes a method for preparing reduced graphene oxide (RGO) coatings with iron oxide nanoparticles (Fex−1Ox), which exhibit improved adhesion strength and oxidation resistance on steel substrates. A suspension that contained a mixture of graphene oxide (GO) and graphene oxide with Fex−1Ox (GO/Fex−1Ox) was formulated and applied to a large area on a steel substrate using electrophoretic deposition. Mechanical and electrochemical characterizations of the RGO and RGO/Fex−1Ox coatings were conducted after thermal reduction at 810 °C in a 10 % Ar/H2 atmosphere. A 138 % improvement in adhesion tensile strength was measured using a mechanical test derived from the standard pull-out test. Moreover, the enhanced oxidation resistances of RGO and RGO/Fex−1Ox coatings were confirmed after thermal reduction using electrochemical impedance spectroscopy and the potentiodynamic polarization method. From calculation of corrosion rate, RGO/Fex−1Ox coatings were corroded by 4 and 13 times slower than RGO coatings and bare steel, respectively. These results suggest that graphene coatings with iron oxide nanoparticles could serve as effective adhesion-promoting intermediary layers that retard steel corrosion in certain applications.
Dynamic variations in coastal water turbidity are key to understanding the sedimentary processes on the west coast of the Korean Peninsula, which has vast tidal flats and a sedimentary environment ...affected by semi-diurnal tides. The aim of this study is to investigate temporal variations in total suspended matter (TSM) distribution along a coastal region using Geostationary Ocean Color Imager (GOCI), the world's first geostationary ocean color observation satellite. TSM concentrations and water-leaving reflectance measured on the coastal water surface in southern Gyeonggi Bay were used to develop an empirical TSM algorithm. TSM maps were generated from the GOCI images at hourly intervals to examine temporal variations in TSM concentrations. Validation of the maps (via comparisons with in situ measurements) showed that the empirical TSM algorithm had been effectively employed. A comparison with the MODIS-derived TSM concentration also supported the reliability of the maps. GOCI-derived TSM at 1-h intervals successfully represented hourly variations in TSM according to the tidal status. In conclusion, the temporal dynamics of sediment movement with the tidal cycle can be effectively estimated on the west coast of the Korean Peninsula using GOCI.
•GOCI enables an hourly monitoring of variations in coastal water properties.•An empirical TSM algorithm for turbid water was effectively developed and employed.•Comparison between GOCI- and MODIS-derived TSM supported the reliability of the maps.•Temporal dynamics of sediment movement with the tidal cycle can be estimated.
Abstract
Novel crosslinking bio polyurethane based polymeric solid–solid phase change materials (SSPCM) were synthesized using castor oil (CO) based hyperbranched polyols as crosslinkers. CO-based ...hyperbranched polyols were synthesized by grafting 1-mercaptoethanol or α–thioglycerol via a thiol-ene click reaction method (coded as COM and COT, respectively). Subsequently, the three SSPCMs were synthesized by a two-step prepolymer method. Polyethylene glycol was used as the phase change material in the SSPCMs, while the CO-based hyperbranched polyols and two types of diisocyanate (hexamethylene diisocyanate (HDI) and 4,4'-diphenylmethane diisocyanate) served as the molecular frameworks. Fourier transform infrared spectroscopy indicated the successful synthesis of the SSPCMs. The solid–solid transition of the prepared SSPCMs was confirmed by X-ray diffraction analysis and polarized optical microscopy. The thermal transition properties of the SSPCMs were analyzed by differential scanning microscopy. The isocyanate and crosslinker types had a significant influence on the phase transition properties. The SSPCM samples prepared using HDI and COT exhibited the highest phase transition enthalpy of 126.5 J/g. The thermal cycling test and thermogravimetric analysis revealed that SSPCMs exhibit outstanding thermal durability. Thus, the novel SSPCMs based on hyperbranched polyols have great potential for application as thermal energy storage materials.
The proposed single-ended transmitter for memory interfaces is an impedance-matched transmitter that utilizes a single ring-oscillator-based time-domain ZQ calibration. This ZQ calibration technique ...eliminates the offsets by using a gain-controlled ring oscillator with late-case forcing, resulting in low maximum/average error rates. The transmitter incorporates a phase equalization method to compensate for pre-cursor inter-symbol interference (ISI) without affecting the impedance matching achieved by ZQ calibration. This phase equalization is implemented by minimizing hardware to overcome the design complexity of conventional phase equalization and reduce power consumption. The prototype chip is fabricated in the 65-nm CMOS process. The transmitter and the ZQ calibration scheme occupy an area of 0.074 and 0.041 mm<inline-formula> <tex-math notation="LaTeX">^{2}</tex-math> </inline-formula>, respectively. The proposed ZQ calibration achieves a maximum error rate of 1.5% and an average error rate of 0.7%. In addition, the transmitter achieves an energy efficiency of 1.145 pJ/bit and an FoM of 0.11 pJ/bit/(dB/pin) at 12 Gb/s.
To enhance the crack propagation and initiation properties and heat deflection temperature of poly(lactic acid) (PLA), PLA/poly(1,4-cyclohexanedimethylene isosorbide terephthalate) (PEICT) blend ...systems were prepared and glass fibers (GF) were incorporated as reinforcements. Due to high shear force during extrusion and injection molding the length of GF was reduced and was oriented towards the flow direction. Although the reinforcing effect of the GF deviated from the theoretical values calculated by the Halpin-Tsai equation, both tensile and flexural properties were greatly enhanced with increasing GF content. Dynamic mechanical and thermal testing showed improved storage modulus throughout the entire temperature range showing outstanding reinforcing ability. By incorporating GF into the PLA/PEICT blend, the crack propagation and initiation properties were enhanced compared to pristine PLA. Such an increase in crack propagation properties was the result of enhanced modulus with the added GF. Moreover, because of the increased modulus, the heat deflection temperatures of the GF reinforced blends were drastically increased showing a value of 91.4 °C at 20 wt% GF loading. The high performance reached by the biomass-based composites developed in this research shows great possibility of replacing these conventional petroleum-based polymer systems.
The PLA/PEICT/GF composite newly presented in this study demonstrated high impact strength and thermal properties.
We recently established a long‐term SARS‐CoV‐2 infection model using lung‐cancer xenograft mice and identified mutations that arose in the SARS‐CoV‐2 genome during long‐term propagation. Here, we ...applied our model to the SARS‐CoV‐2 Delta variant, which has increased transmissibility and immune escape compared with ancestral SARS‐CoV‐2. We observed limited mutations in SARS‐CoV‐2 Delta during long‐term propagation, including two predominant mutations: R682W in the spike protein and L330W in the nucleocapsid protein. We analyzed two representative isolates, Delta‐10 and Delta‐12, with both predominant mutations and some additional mutations. Delta‐10 and Delta‐12 showed lower replication capacity compared with SARS‐CoV‐2 Delta in cultured cells; however, Delta‐12 was more lethal in K18‐hACE2 mice compared with SARS‐CoV‐2 Delta and Delta‐10. Mice infected with Delta‐12 had higher viral titers, more severe histopathology in the lungs, higher chemokine expression, increased astrocyte and microglia activation, and extensive neutrophil infiltration in the brain. Brain tissue hemorrhage and mild vacuolation were also observed, suggesting that the high lethality of Delta‐12 was associated with lung and brain pathology. Our long‐term infection model can provide mutant viruses derived from SARS‐CoV‐2 Delta and knowledge about the possible contributions of emergent mutations to the properties of new variants.
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