A multi-exponential function (ME) is proposed to depict the highly nonlinear soil water retention curve and hydraulic conductivity function. Then, semi-analytical solution of pore-water pressure in ...an unsaturated infinite slope at steady state is derived using ME to depict soil hydraulic properties. The solution is verified with experimental and numerical results. It is found that ME can better describe the highly nonlinear hydraulic properties of soil than the single exponential function (SE), which is commonly-used previously. At steady state, the adoption of SE results in overestimating negative pore-water pressure (PWP; i.e., matric suction) by about 25 kPa and slope’s factor of safety (FOS) by 100% under rainfall, but underestimating negative PWP by about 50 kPa under evaporation. The difference between PWP and FOS calculated by using SE and ME becomes more significant for soil with bimodal hydraulic conductivity function than that with unimodal one. This difference reduces at a larger slope angle and deeper depth. Moreover, this difference generally increases at a lower SME/SSE, where SME and SSE represent the suction at which the unsaturated hydraulic conductivity expressed by ME and SE equals the applied rainfall intensity or evaporation rate, respectively. When SME/SSE is greater than 0.1, the difference basically diminishes.
A dedicated platform for multi-disciplinary research with highly charged ions has been constructed, and an all-permanent magnet ECR ion source was built and installed in the beamline. Five ...experimental terminals are established for interdisciplinary Research. The high voltage supplied to the platform has reached 320 kV. The commissioning of the platform is successful, different ion beams have been provided for experimental studies, and the current status will be reported.
Somatic hypermutation (SHM), initiated by activation-induced cytidine deaminase (AID), generates mutations in the antibody-coding sequence to allow affinity maturation. Why these mutations ...intrinsically focus on the three nonconsecutive complementarity-determining regions (CDRs) remains enigmatic. Here, we found that predisposition mutagenesis depends on the single-strand (ss) DNA substrate flexibility determined by the mesoscale sequence surrounding AID deaminase motifs. Mesoscale DNA sequences containing flexible pyrimidine-pyrimidine bases bind effectively to the positively charged surface patches of AID, resulting in preferential deamination activities. The CDR hypermutability is mimicable in in vitro deaminase assays and is evolutionarily conserved among species using SHM as a major diversification strategy. We demonstrated that mesoscale sequence alterations tune the in vivo mutability and promote mutations in an otherwise cold region in mice. Our results show a non-coding role of antibody-coding sequence in directing hypermutation, paving the way for the synthetic design of humanized animal models for optimal antibody discovery and explaining the AID mutagenesis pattern in lymphoma.
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•AID activity on single-strand DNA per se shapes the CDR-preferential SHM profile•Non-coding function of DNA at the mesoscale level directs AID deamination in vivo•Flexibility of single-strand DNA substrate contributes to AID substrate preference•DNA alteration can make a cold FR hot
Somatic hypermutation in antibody-coding sequences preferentially occurs within specific regions; this study uncovers that the intrinsic single-stranded DNA flexibility within the regions confers the specificity.
•Transient evaporation method was proposed to measure the WRC of structured soils.•Non-invasive TDR probes were developed to allow the measurement of soil water content without penetration.•Compliant ...sampling volume of the TDR and the tensiometer is important to obtain accurate WRC using transient method.
Transient evaporation method is promising for rapid measurement of soil water retention curve (WRC). Existing apparatuses of transient evaporation method are not ideal for measuring the WRC of structured soils because of the sample disturbance induced by invasive water content probes used. In this study, non-invasive TDR probes with different waveguide layouts (i.e., different number of conductors and waveguide length) were developed to measure the WRC of loess during transient evaporation, while the soil suction is recorded through a tensiometer. Results show that the WRCs of undisturbed and remolded loess measured by a three-conductor non-invasive TDR probe are in good agreement with the results of pressure plate tests. The differences in the air entry value (AEV) and desorption rate between the WRCs measured by the transient evaporation method and the pressure plate measurement are less than 10 %. On the other hand, the WRCs measured by a two-conductor non-invasive TDR probe underestimate the water content for a given suction. The AEV of undisturbed and remolded loess determined by the transient evaporation method is 66.7 % and 112.9 % smaller than the results of pressure plate measurements, respectively. The underestimation of the two-conductor non-invasive TDR probe in measuring the WRC of loess can be attributed to the fact that the vertical sampling range of two-conductor non-invasive TDR probe is two times greater than that of the tensiometer. The results in this study show the effectiveness of using the non-invasive TDR probe along with a tensiometer for measuring the WRC. More importantly, great caution should be taken on compliant sampling volume of the non-invasive TDR probe and tensiometer to obtain accurate WRC measurements.
Southern China has a humid climate and often receives rainfalls that are of high intensity and (or) long duration. This paper investigates the performance of an inclined three-layer cover with ...capillary barrier effect (CCBE) comprising silt, sand, and gravel, for usage under humid climatic conditions. Physical modeling tests were carried out to observe the response of the three-layer CCBE system to a continuous heavy rainfall of about 70 mm/h. The layered cover model, housed in a 2 m long and 1 m wide instrumented box, is made up of 0.2 m thick silt, 0.1 m thick sand, and 0.1 m thick gravel, and the inclination of the model is 1V:3H. The movement of wetting front, changes in soil suction, and the primary components of water balance were measured during the operation of the physical models. The experimental data was used to calibrate the hydraulic parameters of the numerical model using the unsaturated flow software, SVFlux. Numerical modeling was subsequently carried out on a 60 m long inclined CCBE system to investigate the effective length of lateral diversion under prolonged rainfall. The main findings of the experimental and numerical studies are as follows: (i) the physical model tests showed that the response of the three-layer CCBE system to a heavy rainfall of 70 mm/h was different from the previous observations on experiments where the rainfall was less than 1.6 mm/h; (ii) correlation between the physical modeling and the numerical modeling indicated anisotropic behavior with respect to the hydraulic conductivity in the unsaturated sand layer; (iii) the long inclined, three-layer CCBE system (i.e., 0.6 m thick silt, 0.2 m thick sand, and 0.2 m thick gravel) had an effective length of lateral diversion over 10 m for 30 days of prolonged rainfall (i.e., 1080 mm in total).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Deficiencies in neutrophil NADPH oxidase proteins have been demonstrated in humans with chronic granulomatous disease. However, no spontaneous mutation in murine NADPH oxidase has been reported. In ...this study we report that neutrophils from the diabetic mouse strains, C57BL/6J-m heterozygous lean (lepr(db/+)) and homozygous obese (lepr(db/db)) mice produced no superoxide on stimulation. An absence of intact p47(phox) but not other oxidase proteins was observed in both mouse strains through the use of immunoblotting. Molecular analysis by reverse transcriptase-polymerase chain reaction identified three abnormal p47phox mRNA transcripts. Sequencing of genomic DNA of p47(phox) revealed a point mutation at the -2 position of exon 8, which is consistent with aberrant splicing of the p47(phox) transcript. These results indicate that the C57BL/6J-m db/db and db/+ mice are the first spontaneously derived murine model of NADPH oxidase deficiency involving a p47(phox) mutation.
Breast cancer screening is a topic of hot debate, and currently no general consensus has been reached on starting and ending ages and screening intervals, in part because of a lack of precise ...estimations of the benefit-harm ratio. Simulation models are often applied to account for the expected benefits and harms of regular screening; however, the degree to which the model outcomes are reliable is not clear. In a recent systematic review, we therefore aimed to assess the quality of published simulation models for breast cancer screening of the general population. The models were scored according to a framework for qualitative assessment. We distinguished seven original models that utilized a common model type, modelling approach, and input parameters. The models predicted the benefit of regular screening in terms of mortality reduction; and overall, their estimates compared well to estimates of mortality reduction from randomized controlled trials. However, the models did not report on the expected harms associated with regular screening. We found that current simulation models for population breast cancer screening are prone to many pitfalls; their outcomes bear a high overall risk of bias, mainly because of a lack of systematic evaluation of evidence to calibrate the input parameters and a lack of external validation. Our recommendations concerning future modelling are therefore to use systematically evaluated data for the calibration of input parameters, to perform external validation of model outcomes, and to account for both the expected benefits and the expected harms so as to provide a clear balance and cost-effectiveness estimation and to adequately inform decision-makers.
The amount of leachate generation rate in MSW landfills is often underestimated during design phase in China. A water balance model of a valley landfill, whose size is 400 m long, 500 m wide and 50 m ...thick, is created to investigate the influences of initial moisture content of waste on source and production of leachate. The 50 m thick waste mass is assumed to be 5 layers. Each layer is 10 m thick with a filling period of 2 years. The leachate mainly comes from precipitation and from squeezed pore water of waste. It is found that higher initial moisture content of waste leads to higher amounts of squeezed leachate and total leachate generation rate, and also results in a high ratio of squeezed leachate to total leachate generation rate. For the cases that the initial moisture contents of waste are 27%, 40%, 50%, and 60%, the amounts of total leachate generation rate are 272, 583, 823 and 1 063 m3 x d(-1), respectively, and the amounts of squeezed leachate are--144, 168, 408, and 647 m3 x d(-1), respectively.
Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide ...association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (P
ranging from 2.79 × 10
to 4.79 × 10
). By incorporating the PRS into EBV-serology-based NPC screening, the test's positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
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