Background
The aim of this study was to investigate the prevalence of epidemiologic and physician‐diagnosed pollen‐induced AR (PiAR) in the grasslands of northern China and to study the impact of the ...intensity and time of pollen exposure on PiAR prevalence.
Methods
A multistage, clustered and proportionately stratified random sampling with a field interviewer‐administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count.
Results
A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05).
Conclusion
Pollen‐induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Programmable RNA editing enables reversible recoding of RNA information for research and disease treatment. Previously, we developed a programmable adenosine-to-inosine (A-to-I) RNA editing approach ...by fusing catalytically inactivate RNA-targeting CRISPR-Cas13 (dCas13) with the adenine deaminase domain of ADAR2. Here, we report a cytidine-to-uridine (C-to-U) RNA editor, referred to as RNA Editing for Specific C-to-U Exchange (RESCUE), by directly evolving ADAR2 into a cytidine deaminase. RESCUE doubles the number of mutations targetable by RNA editing and enables modulation of phosphosignaling-relevant residues. We apply RESCUE to drive β-catenin activation and cellular growth. Furthermore, RESCUE retains A-to-I editing activity, enabling multiplexed C-to-U and A-to-I editing through the use of tailored guide RNAs.
The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated genes (Cas) adaptive immune system defends microbes against foreign genetic elements via DNA or RNA-DNA ...interference. We characterize the class 2 type VI CRISPR-Cas effector C2c2 and demonstrate its RNA-guided ribonuclease function. C2c2 from the bacterium Leptotrichia shahii provides interference against RNA phage. In vitro biochemical analysis shows that C2c2 is guided by a single CRISPR RNA and can be programmed to cleave single-stranded RNA targets carrying complementary protospacers. In bacteria, C2c2 can be programmed to knock down specific mRNAs. Cleavage is mediated by catalytic residues in the two conserved Higher Eukaryotes and Prokaryotes Nucleotide-binding (HEPN) domains, mutations of which generate catalytically inactive RNA-binding proteins. These results broaden our understanding of CRISPR-Cas systems and suggest that C2c2 can be used to develop new RNA-targeting tools.
We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation ...technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.
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Al–12Si components were manufactured by Selective Laser Melting (SLM) using three different atmospheres: argon; nitrogen and helium. The atmosphere type did not affect the part's density or hardness ...and all components reached near full relative density (>97%). The mechanical properties of the components produced in Ar and N2 were superior to those in He, especially the ductility, which has been attributed to the formation of pore clusters in the microstructure. The mechanical properties in SLM-produced components are superior to those produced using conventional method.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Large-scale biophysical circuit models provide mechanistic insights into the micro-scale and macro-scale properties of brain organization that shape complex patterns of spontaneous brain activity. We ...developed a spatially heterogeneous large-scale dynamical circuit model that allowed for variation in local synaptic properties across the human cortex. Here we show that parameterizing local circuit properties with both anatomical and functional gradients generates more realistic static and dynamic resting-state functional connectivity (FC). Furthermore, empirical and simulated FC dynamics demonstrates remarkably similar sharp transitions in FC patterns, suggesting the existence of multiple attractors. Time-varying regional fMRI amplitude may track multi-stability in FC dynamics. Causal manipulation of the large-scale circuit model suggests that sensory-motor regions are a driver of FC dynamics. Finally, the spatial distribution of sensory-motor drivers matches the principal gradient of gene expression that encompasses certain interneuron classes, suggesting that heterogeneity in excitation-inhibition balance might shape multi-stability in FC dynamics.
RNA editing with CRISPR-Cas13 Cox, David B. T.; Gootenberg, Jonathan S.; Abudayyeh, Omar O. ...
Science (American Association for the Advancement of Science),
11/2017, Volume:
358, Issue:
6366
Journal Article
Peer reviewed
Open access
Nucleic acid editing holds promise for treating genetic disease, particularly at the RNA level, where disease-relevant sequences can be rescued to yield functional protein products. Type VI ...CRISPR-Cas systems contain the programmable single-effector RNA-guided ribonuclease Cas13. We profiled type VI systems in order to engineer a Cas13 ortholog capable of robust knockdown and demonstrated RNA editing by using catalytically inactive Cas13 (dCas13) to direct adenosine-to-inosine deaminase activity by ADAR2 (adenosine deaminase acting on RNA type 2) to transcripts in mammalian cells. This system, referred to as RNA Editing for Programmable A to I Replacement (REPAIR), which has no strict sequence constraints, can be used to edit full-length transcripts containing pathogenic mutations. We further engineered this system to create a high-specificity variant and minimized the system to facilitate viral delivery. REPAIR presents a promising RNA-editing platform with broad applicability for research, therapeutics, and biotechnology.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
Different from previous research works on cryogenic titanium alloys with a lamellar microstructure, this study focused on cryogenic tensile properties and the related deformation mechanism of a ...fine-grained near alpha titanium alloy of equiaxed microstructure. The fine-grained equiaxed Ti–3Al–3Mo–3Zr alloy exhibited a remarkably enhanced cryogenic tensile strength until 20 K, but cryogenic ductility decreased sharply as temperature drops. Ultimate tensile strength jumped from 740 MPa at 298 K to 1290 MPa at 77 K and to 1535 MPa at 20 K, while elongation-to-fracture dropped from 20.0% to 12.5% and to 4.0%, respectively. Sharp decline of cryogenic ductility was considered to be directly influenced by the high-angle misoriented equiaxed α-Ti grains. Because dislocation motion got much difficult and twinning could not operate extensively in the fine equiaxed microstructure at cryogenic temperatures. Besides, slip and twinning could not transfer across α-Ti grain boundaries or α/β phase interfaces, resulting in premature cracking. Different from deformation of traditional counterpart with a lamellar microstructure, prismatic and basal slips invariably dominated at 298, 77 and 20 K. Only in certain α-Ti grains whose parallel to loading direction, {10 1‾ 2} type tension twins operated at 77 and 20 K. The present fine-grained near α-Ti alloy with an equiaxed microstructure is suggested to be applied at temperature not lower than 77 K.
•Fine-grained near α-Ti alloy of equiaxed structure exhibits satisfying ductility until 77 K.•Low ductility at 20 K is due to the enhanced difficulty of slip and insufficient twinning.•Prismatic and pyramidal slips dominate tensile deformation at 77 and 20 K.•{10 1‾ 2} twins prefer to occur in oriented α-Ti grains and promote slip deformation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We report constraints on the dark photon effective kinetic mixing parameter (κ) with data taken from two p-type point-contact germanium detectors of the CDEX-10 experiment at the China Jinping ...Underground Laboratory. The 90% confidence level upper limits on κ of solar dark photon from 205.4 kg-day exposure are derived, probing new parameter space with masses (m_{V}) from 10 to 300 eV/c^{2} in direct detection experiments. Considering dark photon as the cosmological dark matter, limits at 90% confidence level with m_{V} from 0.1 to 4.0 keV/c^{2} are set from 449.6 kg-day data, with a minimum of κ=1.3×10^{-15} at m_{V}=200 eV/c^{2}.
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We present a detailed report on sterile neutrino oscillation and 235Uν¯e energy spectrum measurement results from the PROSPECT experiment at the highly enriched High Flux Isotope Reactor (HFIR) at ...Oak Ridge National Laboratory. In 96 calendar days of data taken at an average baseline distance of 7.9 m from the center of the 85 MW HFIR core, the PROSPECT detector has observed more than 50,000 interactions of νe produced in beta decays of 235U fission products. New limits on the oscillation of ν¯e to light sterile neutrinos have been set by comparing the detected energy spectra of ten reactor-detector baselines between 6.7 and 9.2 meters. Measured differences in energy spectra between baselines show no statistically significant indication of ν¯e to sterile neutrino oscillation and disfavor the reactor antineutrino anomaly best-fit point at the 2.5σ confidence level. The reported 235U ν¯e energy spectrum measurement shows excellent agreement with energy spectrum models generated via conversion of the measured 235U beta spectrum, with a χ2/d.o.f. of 31/31. PROSPECT is able to disfavor at 2.4σ confidence level the hypothesis that 235U ν¯e are solely responsible for spectrum discrepancies between model and data obtained at commercial reactor cores. A data-model deviation in PROSPECT similar to that observed by commercial core experiments is preferred with respect to no observed deviation, at a 2.2σ confidence level.
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