The macroscopic mechanical behavior of granular materials is closely related to the fabric anisotropy and contact force anisotropy. In order to investigate the microevolution of fabric and force ...anisotropy of rock masses containing non-coplanar intermittent joints under direct shear loading, this paper establishes a numerical model using the particle flow code (PFC) based on the distinct element method (DEM) and investigates the effects of non-coplanar intermittent joints on the evolutions in the fabric and force anisotropy and the distributions of contact forces of rock specimens by setting up specimens with different ligament angles of joints. Meanwhile, the shear strength, deformation characteristics and failure mode, energy dissipation were analyzed to deepen the understanding of the macroscopic mechanical behavior of the specimens from the microscopic mechanism. Three anisotropic tensors
a
ij
c
,
a
ij
n
and
a
ij
t
are defined to characterize the anisotropic behavior of the granular materials which can show the evolution law of fabric and mechanical anisotropy of the system under direct shear load. The findings indicate that the degree of fabric anisotropy increases with increasing ligament, and the length of the load side significantly influences the initial mechanical anisotropy of the specimen. Concurrently, a rise in the ligament angle impedes the progression of anisotropy within the specimen, leading to a substantial reduction in the macroscopic mechanical strength of the rock.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Genome-wide association studies (GWAS), especially on rare diseases, may necessitate exchange of sensitive genomic data between multiple institutions. Since genomic data sharing is often infeasible ...due to privacy concerns, cryptographic methods, such as secure multiparty computation (SMC) protocols, have been developed with the aim of offering privacy-preserving collaborative GWAS. Unfortunately, the computational overhead of these methods remain prohibitive for human-genome-scale data. Here we introduce SkSES (https://github.com/ndokmai/sgx-genome-variants-search), a hardware-software hybrid approach for privacy-preserving collaborative GWAS, which improves the running time of the most advanced cryptographic protocols by two orders of magnitude. The SkSES approach is based on trusted execution environments (TEEs) offered by current-generation microprocessors-in particular, Intel's SGX. To overcome the severe memory limitation of the TEEs, SkSES employs novel 'sketching' algorithms that maintain essential statistical information on genomic variants in input VCF files. By additionally incorporating efficient data compression and population stratification reduction methods, SkSES identifies the top k genomic variants in a cohort quickly, accurately and in a privacy-preserving manner.
With mounting preclinical and clinical evidences on the prominent roles of the tumor microenvironment (TME) played during carcinogenesis, the TME has been recognized and used as an important ...onco‐therapeutic target during the past decade. Delineating our current knowledge on TME components and their functionalities can help us recognize novel onco‐therapeutic opportunities and establish treatment modalities towards desirable anti‐cancer outcome. By identifying and focusing on primary cellular components in the TME, that is, tumor‐infiltrating lymphocytes, tumor‐associated macrophages, cancer‐associated fibroblasts and mesenchymal stem cells, we decomposed their primary functionalities during carcinogenesis, categorized current therapeutic approaches utilizing traits of these components, and forecasted possible benefits that cold atmospheric plasma, a redox modulating tool with selectivity against cancer cells, may convey by targeting the TME. Our insights may open a novel therapeutic avenue for cancer control taking advantages of redox homeostasis and immunostasis.
CAP can possibly enhance tumor antigen secretion and enhance CD8+ TIL cytotoxicity, potentially repolarize TAMs from the M2 to the M1 state, modulate p53‐driven CAF hierarchy towards enhanced drug sensitivity, block MSCs differentiation to CAFs that is associated with reduced cancer stemness, and function as the cargo of MSCs or their derived exosomes for enhanced delivery to the tumor loci.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Top-down homogeneous multiplexed tandem mass (HomMTM) spectra are generated from modified proteoforms of the same protein with different post-translational modification patterns. They are frequently ...observed in the analysis of ultramodified proteins, some proteoforms of which have similar molecular weights and cannot be well separated by liquid chromatography in mass spectrometry analysis.
We formulate the top-down HomMTM spectral identification problem as the minimum error k-splittable flow problem on graphs and propose a graph-based algorithm for the identification and quantification of proteoforms using top-down HomMTM spectra.
Experiments on a top-down mass spectrometry data set of the histone H4 protein showed that the proposed method identified many proteoform pairs that better explain the query spectra than single proteoforms.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Using density functional theory (DFT) calculations, we researched the different anions adsorption on the graphene and found that anions can be stably adsorbed on the graphene surface due to the ...anion-π interaction. The adsorption energy decreased as the order of HPO
4
2–
> SO
4
2–
> F
–
> CH
3
COO
–
> ClO
3
–
> NO
3
–
> ClO
4
–
> SCN
–
> Cl
–
> Br
–
. The adsorption energy markedly increased as the valence of anion increased from negative monovalence (< -20 kcal/mol) to negative bivalence (> -40 kcal/mol). The energy decomposition analysis (EDA) showed that anion-π interaction is mainly induced by orbital effect. This work provides new insights for understanding Hofmeister effect at graphene interface from the molecular level and indicates that the anion-π interaction cannot be ignored at the interface, especially for the substrate with π-electron-rich carbon–based nanomaterials.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Retinoic acid(RA), an embryonic morphogen, regulates cell differentiation. Endocytosis regulates receptor signaling that governs such RA-directed cellular processes. Vacuolin-1 is a small molecule ...that disrupts endocytosis, motivating interest in its effect on RA-induced differentiation/arrest. In HL-60 myeloblastic-leukemia cells, RA causes differentiation evidenced by a progression of cell-surface and functional markers, CD38, CD11b, and finally reactive oxygen species(ROS) production and G1/0 cell cycle arrest in mature cells.
We found that Vacuolin-1 enhanced RA-induced CD11b, ROS and G1/0 arrest, albeit not CD38. Enhanced CD11b expression was associated with enhanced activation of Focal Adhesion Kinase(FAK). Adding vacuolin-1 enhanced RA-induced tyrosine phosphorylation of FAK, Src Family Kinases(SFKs), and the adaptor protein, SLP-76, expression of which is known to drive RA-induced differentiation. Depleting CD11b cripples late stages of progressive myeloid differentiation, namely G1/0 arrest and inducible ROS production, but not expression of CD38. Loss of NUMB, a protein that supports early endosome maturation, affected RA-induced ROS and G1/0 arrest, but not CD38 expression.
Hence there appears to be a novel CD11b/FAK/LYN/SLP-76 axis subject to endosome regulation which contributes to later stages of RA-induced differentiation. The effects of vacuolin-1 thus suggest a model where RA-induced differentiation consists of progressive stages driven by expression of sequentially-induced receptors.
The plant-specific transcription factor TEOSINTE BRANCHED, CYCLOIDEA, AND PROLIFERATING CELL FACTOR (TCP) gene family plays vital roles in various biological processes, including growth and ...development, hormone signaling, and stress responses. However, there is a limited amount of information regarding the TCP gene family in roses (Rosa sp.). In this study, we identified 18 TCP genes in the rose genome, which were further classified into two subgroups (Group A and Group B) via phylogenetic analysis. Comprehensive characterization of these TCP genes was performed, including gene structure, motif composition, chromosomal location, and expression profiles. Synteny analysis revealed that a few TCP genes are involved in segmental duplication events, indicating that these genes played an important role in the expansion of the TCP gene family in roses. This suggests that segmental duplication events have caused the evolution of the TCP gene family and may have generated new functions. Our study provides an insight into the evolutionary and functional characteristics of the TCP gene family in roses and lays a foundation for the future exploration of the regulatory mechanisms of TCP genes in plant growth and development.
Computational identification and quantification of distinct microbes from high throughput sequencing data is crucial for our understanding of human health. Existing methods either use accurate but ...computationally expensive alignment-based approaches or less accurate but computationally fast alignment-free approaches, which often fail to correctly assign reads to genomes. Here we introduce CAMMiQ, a combinatorial optimization framework to identify and quantify distinct genomes (specified by a database) in a metagenomic dataset. As a key methodological innovation, CAMMiQ uses substrings of variable length and those that appear in two genomes in the database, as opposed to the commonly used fixed-length, unique substrings. These substrings allow to accurately decouple mixtures of highly similar genomes resulting in higher accuracy than the leading alternatives, without requiring additional computational resources, as demonstrated on commonly used benchmarking datasets. Importantly, we show that CAMMiQ can distinguish closely related bacterial strains in simulated metagenomic and real single-cell metatranscriptomic data.
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