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1.
Bioresour Technol ; 332: 125047, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33839509

RESUMO

Methanotrophs can oxidize methane as the sole carbon and energy, and the resulting intermediate products can be simultaneously utilized by coexistent denitrifying bacteria to remove the nitrogen, which named Aerobic Methane Oxidation Coupled to Denitrification (AME-D). In this paper, an AME-D system was built in an improved denitrification bio-filter, to analyze the nitrogen removal efficiency and mechanism. The maximum TN removal rate reached 95.05%. As shown in Raman spectroscopy, in the effluent wave crests generated by the symmetric expansion and contraction of NO3- disappeared, and the distortion of olefin CH2 and C-OH stretching of alcohols appeared. Metagenomics revealed Methylotenera and Methylobacter were the dominated methanotrophs. There was a completed methane and nitrogen metabolism pathway with the synergism of nxrAB, narGHI, nasAB, pmo-amoABC and mmo genes. Dissimilatory reduction pathway was the primary nitrate removal pathway. Moreover, Bradyrhizobium could participate in methane and nitrogen metabolism simultaneously.


Assuntos
Desnitrificação , Metano , Reatores Biológicos , Redes e Vias Metabólicas , Metagenômica , Nitrogênio , Oxirredução
2.
Micromachines (Basel) ; 12(3)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33800963

RESUMO

Compared with a traditional optical system, the single-lens curved compound eye imaging system has superior optical performance, such as a large field of view (FOV), small size, and high portability. However, defocus and low resolution hinder the further development of single-lens curved compound eye imaging systems. In this study, the design of a nonuniform curved compound eye with multiple focal lengths was used to solve the defocus problem. A two-step gas-assisted process, which was combined with photolithography, soft photolithography, and ultraviolet curing, was proposed for fabricating the ommatidia with a large numerical aperture precisely. Ommatidia with high resolution were fabricated and arranged in five rings. Based on the imaging experimental results, it was demonstrated that the high-resolution and small-volume single-lens curved compound eye imaging system has significant advantages in large-field imaging and rapid recognition.

3.
Genome Res ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33832989

RESUMO

Steps of mRNA maturation are important gene regulatory events that occur in distinct cellular locations. However, transcriptomic analyses often lose information on the subcellular distribution of processed and unprocessed transcripts. We generated extensive RNA-seq datasets to track mRNA maturation across subcellular locations in mouse embryonic stem cells, neuronal progenitor cells, and postmitotic neurons. We find disparate patterns of RNA enrichment between the cytoplasmic, nucleoplasmic, and chromatin fractions, with some genes maintaining more polyadenylated RNA in chromatin than in the cytoplasm. We bioinformatically defined four regulatory groups for intron retention, including complete cotranscriptional splicing, complete intron retention in the cytoplasmic RNA, and two intron groups present in nuclear and chromatin transcripts but fully excised in cytoplasm. We find that introns switch their regulatory group between cell types, including neuronally excised introns repressed by polypyrimidine track binding protein 1 (PTBP1). Notably, transcripts for the neuronal gamma-aminobutyric acid type B receptor subunit 1 (GABBR1) are highly expressed in mESC but are absent from the cytoplasm. Instead, incompletely spliced Gabbr1 RNA remains sequestered on chromatin, where it is bound by PTBP1 similar to certain long noncoding RNAs. Upon neuronal differentiation, Gabbr1 RNA becomes fully processed and exported for translation. Thus, splicing repression and chromatin anchoring of RNA combine to allow posttranscriptional regulation of Gabbr1 over development. For this and other genes, polyadenylated RNA abundance does not indicate functional gene expression. Our datasets provide a rich resource for analyzing many other aspects of mRNA maturation in subcellular locations and across development.

4.
Sci Rep ; 11(1): 8064, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33850172

RESUMO

The myodural bridge (MDB) connects the suboccipital musculature to the spinal dura mater (SDM) as it passed through the posterior atlanto-occipital and the atlanto-axial interspaces. Although the actual function of the MDB is not understood at this time, it has recently been proposed that head movement may assist in powering the movement of cerebrospinal fluid (CSF) via muscular tension transmitted to the SDM via the MDB. But there is little information about it. The present study utilized dogs as the experimental model to explore the MDB's effects on the CSF pressure (CSFP) during stimulated contractions of the suboccipital muscles as well as during manipulated movements of the atlanto-occiptal and atlanto-axial joints. The morphology of MDB was investigated by gross anatomic dissection and by histological observation utilizing both light microscopy and scanning electron microscopy. Additionally biomechanical tensile strength tests were conducted. Functionally, the CSFP was analyzed during passive head movements and electrical stimulation of the suboccipital muscles, respectively. The MDB was observed passing through both the dorsal atlanto-occipital and the atlanto-axial interspaces of the canine and consisted of collagenous fibers. The tensile strength of the collagenous fibers passing through the dorsal atlanto-occipital and atlanto-axial interspaces were 0.16 ± 0.04 MPa and 0.82 ± 0.57 MPa, respectively. Passive head movement, including lateral flexion, rotation, as well as flexion-extension, all significantly increased CSFP. Furthermore, the CSFP was significantly raised from 12.41 ± 4.58 to 13.45 ± 5.16 mmHg when the obliques capitis inferior (OCI) muscles of the examined specimens were electrically stimulated. This stimulatory effect was completely eliminated by severing the myodural bridge attachments to the OCI muscle. Head movements appeared to be an important factor affecting CSF pressure, with the MDB of the suboccipital muscles playing a key role this process. The present study provides direct evidence to support the hypothesis that the MDB may be a previously unappreciated significant power source (pump) for CSF circulation.

5.
Nano Lett ; 21(6): 2642-2649, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33709720

RESUMO

Integrating machine learning with surface-enhanced Raman scattering (SERS) accelerates the development of practical sensing devices. Such integration, in combination with direct detection or indirect analyte capturing strategies, is key to achieving high predictive accuracies even in complex matrices. However, in-depth understanding of spectral variations arising from specific chemical interactions is essential to prevent model overfit. Herein, we design a machine-learning-driven "SERS taster" to simultaneously harness useful vibrational information from multiple receptors for enhanced multiplex profiling of five wine flavor molecules at parts-per-million levels. Our receptors employ numerous noncovalent interactions to capture chemical functionalities within flavor molecules. By strategically combining all receptor-flavor SERS spectra, we construct comprehensive "SERS superprofiles" for predictive analytics using chemometrics. We elucidate crucial molecular-level interactions in flavor identification and further demonstrate the differentiation of primary, secondary, and tertiary alcohol functionalities. Our SERS taster also achieves perfect accuracies in multiplex flavor quantification in an artificial wine matrix.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33735414

RESUMO

The effects of meteorological factors on health outcomes have gained popularity due to climate change, resulting in a general rise in temperature and abnormal climatic extremes. Instead of the conventional cross-sectional analysis that focuses on the association between a predictor and the single dependent variable, the distributed lag non-linear model (DLNM) has been widely adopted to examine the effect of multiple lag environmental factors health outcome. We propose several novel strategies to model mortality with the effects of distributed lag temperature measures and the delayed effect of mortality. Several attempts are derived by various statistical concepts, such as summation, autoregressive, principal component analysis, baseline adjustment, and modeling the offset in the DLNM. Five strategies are evaluated by simulation studies based on permutation techniques. The longitudinal climate and daily mortality data in Taipei, Taiwan, from 2012 to 2016 were implemented to generate the null distribution. According to simulation results, only one strategy, named MVDLNM, could yield valid type I errors, while the other four strategies demonstrated much more inflated type I errors. With a real-life application, the MVDLNM that incorporates both the current and lag mortalities revealed a more significant association than the conventional model that only fits the current mortality. The results suggest that, in public health or environmental research, not only the exposure may post a delayed effect but also the outcome of interest could provide the lag association signals. The joint modeling of the lag exposure and the delayed outcome enhances the power to discover such a complex association structure. The new approach MVDLNM models lag outcomes within 10 days and lag exposures up to 1 month and provide valid results.

7.
Food Chem ; 353: 129439, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33743430

RESUMO

Pu-erh tea is a post-fermentation tea with unique flavor and multiple health benefits. Due to the various microorganisms involved in the post-fermentation process, Pu-erh tea contains highly complex components, which have rich interactions with the gut microbiomes (GMs). Because the structure and homeostasis of GMs are closely related to human wellness and the various diseases progress, the beneficial effects of Pu-erh tea on GMs have a great potential for application in health care. However, there is no systematic summary of the bioactive components of Pu-erh tea, and their effects on the GMs. Here, we review the current studies on the effects of Pu-erh tea and its bioactive components on the structure of GMs as well as on health improvement, and further discuss the relevant quality indicators. This "components - function - indicators" clue will hopefully stimulate the standardization of Pu-erh tea fermentation process and the development of its functional products.

8.
Nanoscale ; 13(12): 5935-5936, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33734271
9.
Sci Total Environ ; 776: 145596, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33652310

RESUMO

Hydrothermal liquefaction (HTL) is a promising thermochemical technology for the treatment of hazardous wastes such as penicillin residue (PR). For the treatment of aqueous waste produced by PR in the HTL process, aqueous phase circulation is an attractive solution, both environmentally and economically. The present study shows that aqueous phase circulation can promote the transfer of organic matter from the aqueous phase to bio-oil. The content of organic acids and alcohols in the aqueous phase decreased significantly, and the bio-oil yield and energy recovery efficiency also increased. Under non-catalytic conditions, the bio-oil yield increased from 26.09 wt% to 33.72 wt%. The use of Na2CO3 as a catalyst further improved the bio-oil yield. After a single aqueous phase circulation, the bio-oil yield increased to 34.63 wt%, and the energy recovery efficiency increased to 66.94%. Under catalytic hydrothermal conditions, the content of organic acids in the bio-oil was reduced using aqueous phase circulations, which improved the quality of the bio-oil. At the same time, the Na2CO3 catalyst promoted the hydrolysis of PR to form small molecule organic matter, inhibited the formation of coke, and reduced the content of carbon, hydrogen and oxygen in the solid residue. An increase of cycle times led to excessive accumulation of Na2CO3, which had a negative impact on the yield of bio-oil. Nitrogen-containing compounds in the bio-oil increased to a certain extent, which renders it necessary to consider denitrification treatments in the future. The work provides a useful reference for further research on the preparation of high quality bio-oil by PR hydrothermal liquefaction.


Assuntos
Biocombustíveis , Penicilinas , Biomassa , Óleos Vegetais , Polifenóis , Temperatura , Água
10.
Trends Pharmacol Sci ; 42(4): 268-282, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33711255

RESUMO

Cancer transcriptomes frequently exhibit RNA dysregulation. As the resulting aberrant transcripts may be translated into cancer-specific proteins, there is growing interest in exploiting RNA dysregulation as a source of tumor antigens (TAs) and thus novel immunotherapy targets. Recent advances in high-throughput technologies and rapid accumulation of multiomic cancer profiling data in public repositories have provided opportunities to systematically characterize RNA dysregulation in cancer and identify antigen targets for immunotherapy. However, given the complexity of cancer transcriptomes and proteomes, important conceptual and technological challenges exist. Here, we highlight the expanding repertoire of TAs arising from RNA dysregulation and introduce multiomic and big data strategies for identifying optimal immunotherapy targets. We discuss extant barriers for translating these targets into effective therapies as well as the implications for future research.

11.
Genome Biol ; 22(1): 77, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33685485

RESUMO

BACKGROUND: A-to-I RNA editing diversifies the transcriptome and has multiple downstream functional effects. Genetic variation contributes to RNA editing variability between individuals and has the potential to impact phenotypic variability. RESULTS: We analyze matched genetic and transcriptomic data in 49 tissues across 437 individuals to identify RNA editing events that are associated with genetic variation. Using an RNA editing quantitative trait loci (edQTL) mapping approach, we identify 3117 unique RNA editing events associated with a cis genetic polymorphism. Fourteen percent of these edQTL events are also associated with genetic variation in their gene expression. A subset of these events are associated with genome-wide association study signals of complex traits or diseases. We determine that tissue-specific levels of ADAR and ADARB1 are able to explain a subset of tissue-specific edQTL events. We find that certain microRNAs are able to differentiate between the edited and unedited isoforms of their targets. Furthermore, microRNAs can generate an expression quantitative trait loci (eQTL) signal from an edQTL locus by microRNA-mediated transcript degradation in an editing-specific manner. By integrative analyses of edQTL, eQTL, and microRNA expression profiles, we computationally discover and experimentally validate edQTL-microRNA pairs for which the microRNA may generate an eQTL signal from an edQTL locus in a tissue-specific manner. CONCLUSIONS: Our work suggests a mechanism in which RNA editing variability can influence the phenotypes of complex traits and diseases by altering the stability and steady-state level of critical RNA molecules.

12.
Biomed Microdevices ; 23(2): 19, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33770288

RESUMO

The effects of six polycyclic aromatic hydrocarbons (PAHs) on the activity of V79 cells were studied by using a miniature electrochemical system based on graphene oxide quantum dots and multiwall carbon nanotubes modified anodized screen printed carbon electrode. The cytotoxicity sequence of PAHs on V79 cells was different with guanine/xanthine (G/X), adenine (A), hypoxanthine (HX), and the end product of purine nucleotide catabolism, uric acid (UA), as biomarkers. The IC50 values measured with UA as the biomarker were the lowest, indicating that UA in cells was more sensitive to PAHs. The cytotoxicity sequence with G/X as the biomarker was the same as that of the MTT assay: pyrene > phenanthrene > benzo[a]pyrene > fluoranthene > fluorene > naphthalene. The cytotoxicity sequences measured by different biomarkers varied, which related to different structures that may influence the expression of the cellular aryl hydrocarbon receptor, gap junctional intercellular communication, and p53 protein. PAHs with different structures played varied roles in cell development and differentiation. Additionally, the electrochemical method was more sensitive than the MTT assay. The miniature electrochemical system enabled the simultaneous detection of four signals in cells, providing more information for multi-parameter evaluation and toxic mechanism study of PAHs and other pollutants.

13.
Sci Rep ; 11(1): 6243, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737533

RESUMO

Maintaining genetic diversity in dog breeds is an important consideration for the management of inherited diseases. We evaluated genetic diversity in Border Collies using molecular and genealogical methods, and examined changes to genetic diversity when carriers for Trapped Neutrophil Syndrome (TNS) and Neuronal Ceroid Lipofuscinosis (NCL) are removed from the genotyped population. Genotype data for 255 Border Collies and a pedigree database of 83,996 Border Collies were used for analysis. Molecular estimates revealed a mean multi-locus heterozygosity (MLH) of 0.311 (SD 0.027), 20.79% of the genome consisted of runs of homozygosity (ROH ) > 1 Mb, effective population size (Ne) was 84.7, and mean inbreeding (F) was 0.052 (SD 0.083). For 227 genotyped Border Collies that had available pedigree information (GenoPed), molecular and pedigree estimates of diversity were compared. A reference population (dogs born between 2005 and 2015, inclusive; N = 13,523; RefPop) and their ancestors (N = 12,478) were used to evaluate the diversity of the population that are contributing to the current generation. The reference population had a Ne of 123.5, a mean F of 0.095 (SD 0.082), 2276 founders (f), 205.5 effective founders (fe), 28 effective ancestors (fa) and 10.65 (SD 2.82) founder genomes (Ng). Removing TNS and NCL carriers from the genotyped population had a small impact on diversity measures (ROH > 1 Mb, MLH, heterozygosity), however, there was a loss of > 10% minor allele frequency for 89 SNPs around the TNS mutation (maximum loss of 12.7%), and a loss of > 5% for 5 SNPs around the NCL mutation (maximum 5.18%). A common ancestor was identified for 38 TNS-affected dogs and 64 TNS carriers, and a different common ancestor was identified for 33 NCL-affected dogs and 28 carriers, with some overlap of prominent individuals between both pedigrees. Overall, Border Collies have a high level of genetic diversity compared to other breeds.

14.
Artif Cells Nanomed Biotechnol ; 49(1): 308-316, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33739906

RESUMO

Triamcinolone acetonide (TA) is widely indicated in the treatment of several ocular disorders, but the free drug suspension limits its clinical benefits and commercial compositions cause adverse ocular effects. In this study, TA was formulated in poly(d,l-lactide-co-glycolide) (PLGA)-chitosan (PLC) nanoparticles (NPs) for the treatment of ocular inflammatory diseases. TA-loaded PLC NPs exhibited excellent anti-inflammatory activity against human corneal epithelial (HCE) cells and significantly reduced the secretion of interleukin (IL)-6 in tumour necrosis factor (TNF)-α activated cells. In a rabbit model, TA-loaded PLC NPs did not show any typical clinical signs of eye inflammation and significantly alleviated inflammatory signs, compared with free TA suspension, at 24 h after a single dose. TA-loaded PLC NPs exhibited a greater aqueous humour transparency (%AHT), compared with that of normal saline (NS) or free TA suspension, indicating reduction in anterior chamber fogginess. Pharmacokinetic analysis of rabbit eyes revealed that TA-loaded PLC NPs peaked at 6 h. Substantial concentrations of TA were observed until 24 h, indicating the superiority of this PLC-based nanocarrier system. Overall, PLC-based NP formulations offer a new approach for the treatment of ocular inflammatory diseases.

15.
Nat Commun ; 12(1): 930, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568643

RESUMO

α-Pyridones and α-pyrones are ubiquitous structural motifs found in natural products and biologically active small molecules. Here, we report an Rh-catalyzed electrochemical vinylic C-H annulation of acrylamides with alkynes, affording cyclic products in good to excellent yield. Divergent syntheses of α-pyridones and cyclic imidates are accomplished by employing N-phenyl acrylamides and N-tosyl acrylamides as substrates, respectively. Additionally, excellent regioselectivities are achieved when using unsymmetrical alkynes. This electrochemical process is environmentally benign compared to traditional transition metal-catalyzed C-H annulations because it avoids the use of stoichiometric metal oxidants. DFT calculations elucidated the reaction mechanism and origins of substituent-controlled chemoselectivity. The sequential C-H activation and alkyne insertion under rhodium catalysis leads to the seven-membered ring vinyl-rhodium intermediate. This intermediate undergoes either the classic neutral concerted reductive elimination to produce α-pyridones, or the ionic stepwise pathway to produce cyclic imidates.

16.
Transbound Emerg Dis ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33559368

RESUMO

The variety and widespread of coronavirus in natural reservoir animals is likely to cause epidemics via interspecific transmission, which has attracted much attention due to frequent coronavirus epidemics in recent decades. Birds are natural reservoir of various viruses, but the existence of coronaviruses in wild birds in central China has been barely studied. Some bird coronaviruses belong to the genus of Deltacoronavirus. To explore the diversity of bird deltacoronaviruses in central China, we tested faecal samples from 415 wild birds in Hunan Province, China. By RT-PCR detection, we identified eight samples positive for deltacoronaviruses which were all from common magpies, and in four of them, we successfully amplified complete deltacoronavirus genomes distinct from currently known deltacoronavirus, indicating four novel deltacoronavirus stains (HNU1-1, HNU1-2, HNU2 and HNU3). Comparative analysis on the four genomic sequences showed that these novel magpie deltacoronaviruses shared three different S genes among which the S genes of HNU1-1 and HNU1-2 showed 93.8% amino acid (aa) identity to that of thrush coronavirus HKU12, HNU2 S showed 71.9% aa identity to that of White-eye coronavirus HKU16, and HNU3 S showed 72.4% aa identity to that of sparrow coronavirus HKU17. Recombination analysis showed that frequent recombination events of the S genes occurred among these deltacoronavirus strains. Two novel putative cleavage sites separating the non-structural proteins in the HNU coronaviruses were found. Bayesian phylogeographic analysis showed that the south coast of China might be a potential origin of bird deltacoronaviruses existing in inland China. In summary, these results suggest that common magpie in China carries diverse deltacoronaviruses with novel genomic features, indicating an important source of environmental coronaviruses closed to human communities, which may provide key information for prevention and control of future coronavirus epidemics.

17.
Sci Total Environ ; 767: 144977, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33636768

RESUMO

Antibiotic fermentation residue (AR) is composed of hazardous organic waste produced by the pharmaceutical industry. AR can be effectively converted into bio-oil by fast pyrolysis, but its high nitrogen content limits the prospect of bio-oil as a fuel resource. In order to further reduce the nitrogen content of AR bio-oil, we have examined the catalytic removal of N and O from penicillin fermentation residue (PR) bio-oil under fast pyrolysis conditions. We have used M/HZSM-5 (M = Fe, Co, Ni, Cu, Zn, Zr, Mo, Ag and Ce) metal catalysts, with a metal oxide content of 10%. Additionally, the effect of mixed and separated catalytic forms on catalytic upgrading were analyzed, and changes in the catalyst itself before and after pyrolysis under separated catalytic conditions were specifically investigated. Our results show that the metal elements in the fresh catalyst will exist in the form of oxides, ions and simple metals. In-situ reduction caused by pyrolysis gas in the catalytic pyrolysis process makes some ionic metals (e.g., Co2+, Cu2+ and Ag+) in the catalyst transform into oxides, and some metal oxides are reduced to simple metals or suboxides (including Fe, Ni, Cu and Mo). The N content in the mixed catalytic bio-oil decreased from 10.09 wt% to Zn/HZSM-5 (6.98 wt%), Co/HZSM-5 (7.1 wt%), Cu/HZSM-5 (7.18 wt%) and Ce/HZSM-5 (7.18 wt%). We also observed significant reduction in the O content (9.77 wt%) with Ag/HZSM-5 (3.75 wt%), Mo/HZSM-5 (6.86 wt%), Ce/HZSM-5 (8.39 wt%) and Fe/HZSM-5 (8.54 wt%) in the separated catalytic bio-oil. The Ni/HZSM-5 catalystcan reduce the organic acid content in bio-oil from 22.9% to 10.8%. The separated catalysis methodology also promoted an increase of hydrocarbons in the bio-oil: Zn/HZSM-5, Ag/HZSM-5, Mo/HZSM-5, Zr/HZSM-5 and Ce/HZSM-5 reached 11.6%, 11.5%, 11.1%, 10.1%, and 8.8%, respectively. Carbon deposition formed by aromatic carbon/graphite carbon, pyrrole and pyridine compounds leads to deactivation of the catalyst.


Assuntos
Biocombustíveis , Penicilinas , Biomassa , Catálise , Fermentação , Temperatura Alta , Óleos Vegetais , Polifenóis
19.
Org Lett ; 23(4): 1209-1215, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33538167

RESUMO

Electrochemically driven, Cp*Ir(III)-catalyzed regioselective annulative couplings of benzoic acids with alkynes have been established herein. The combination of iridium catalyst and electricity not only circumvents the need for stoichiometric amount of chemical oxidant, but also ensures broad reaction compatibility with a wide array of sterically and electronically diverse substrates. This electrochemical approach represents a sustainable strategy as an ideal alternative and supplement to the oxidative annulations methodology to be engaged in the synthesis of isocoumarin derivatives.

20.
Phys Rev Lett ; 126(4): 048002, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33576668

RESUMO

We perform combined x-ray tomography and shear force measurements on a cyclically sheared granular system with highly transient behaviors, and obtain the evolution of microscopic structures and macroscopic shear force during the shear cycle. We explain the macroscopic behaviors of the system based on microscopic processes, including particle level structural rearrangement and frictional contact variation. Specifically, we show how contact friction can induce large structural fluctuations and cause significant shear dilatancy effect for granular materials, and we also construct an empirical constitutive relationship for the macroscopic shear force.

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