Search

DNA mismatch repair (MMR) maintains genome stability primarily by correcting replication errors. MMR deficiency can lead to cancer development and bolsters cancer cell resistance to chemotherapy. However, recent studies have shown that checkpoint blockade therapy is effective in MMR-deficient cancers, thus the ability to identify cancer etiology would greatly benefit cancer treatment. MutS homolog 2 (MSH2) is an obligate subunit of mismatch recognition proteins MutSa (MSH2-MSH6) and MutSß (MSH2-MSH3). Precise regulation of MSH2 is critical, as either over- or underexpression of MSH2 results in an increased mutation frequency. The mechanism by which cells maintain MSH2 proteostasis is unknown. Using functional ubiquitination and deubiquitination assays, we show that the ovarian tumor (OTU) family deubiquitinase ubiquitin aldehyde binding 1 (OTUB1) inhibits MSH2 ubiquitination by blocking the E2 ligase ubiquitin transfer activity. Depleting OTUB1 in cells promotes the ubiquitination and subsequent degradation of MSH2, leading to greater mutation frequency and cellular resistance to genotoxic agents, including the common chemotherapy agents N-methyl-N'-nitro-N-nitrosoguanidine and cisplatin. Taken together, our data identify OTUB1 as an important regulator of MSH2 stability and provide evidence that OTUB1 is a potential biomarker for cancer etiology and therapy. [ABSTRACT FROM AUTHOR]

Somatic mutations on glycine 34 of histone H3 (H3G34) cause pediatric cancers, but the underlying oncogenic mechanism remains unknown. We demonstrate that substituting H3G34 with arginine, valine, or aspartate (H3G34R/V/D), which converts the non-side chain glycine to a large side chain-containing residue, blocks H3 lysine 36 (H3K36) dimethylation and trimethylation by histone methyltransferases, including SETD2, an H3K36-specific trimethyltransferase. Our structural analysis reveals that the H3 "G33-G34" motif is recognized by a narrow substrate channel, and that H3G34/R/V/D mutations impair the catalytic activity of SETD2 due to steric clashes that impede optimal SETD2-H3K36 interaction. H3G34R/V/D mutations also block H3K36me3 from interacting with mismatch repair (MMR) protein MutSα, preventing the recruitment of the MMR machinery to chromatin. Cells harboring H3G34R/V/D mutations display a mutator phenotype similar to that observed in MMR-defective cells. Therefore, H3G34R/V/D mutations promote genome instability and tumorigenesis by inhibiting MMR activity. [ABSTRACT FROM AUTHOR]

Histone H3 trimethylation at lysine 36 (H3K36me3) is an important histone mark involved in both transcription elongation and DNA mismatch repair (MMR). It is known that H3K36me3 recruits the mismatch-recognition protein MutSα to replicating chromatin via its physical interaction with MutSα's PWWP domain, but the exact role of H3K36me3 in transcription is undefined. Using ChIP combined with whole-genome DNA sequencing analysis, we demonstrate here that H3K36me3, together with MutSα, is involved in protecting against mutation, preferentially in actively transcribed genomic regions. We found that H3K36me3 and MutSα are much more co-enriched in exons and actively transcribed regions than in introns and nontranscribed regions. The H3K36me3-MutSα co-enrichment correlated with a much lower mutation frequency in exons and actively transcribed regions than in introns and nontranscribed regions. Correspondingly, depleting H3K36me3 or disrupting the H3K36me3-MutSα interaction elevated the spontaneous mutation frequency in actively transcribed genes, but it had little influence on the mutation frequency in nontranscribed or transcriptionally inactive regions. Similarly, H2O2-induced mutations, which mainly cause base oxidations, preferentially occurred in actively transcribed genes in MMR-deficient cells. The data presented here suggest that H3K36me3-mediated MMR preferentially safeguards actively transcribed genes not only during replication by efficiently correcting mispairs in early replicating chromatin but also during transcription by directly or indirectly removing DNA lesions associated with a persistently open chromatin structure. [ABSTRACT FROM AUTHOR]

Hilbert-Huang transform (HHT) is a popular method to analyze nonlinear and non-stationary data. It has been widely used in geophysical prospecting. This paper analyzes the mode mixing problems of empirical mode decomposition (EMD) and introduces the noncontact measurement and detection of instantaneous seismic attributes using complementary ensemble empirical mode decomposition (CEEMD). Numerical simulation testing indicates that the CEEMD can effectively solve the mode mixing problems of EMD and can provide stronger anti-noise ability. The decomposed results of the synthetic seismic record show that CEEMD has a better ability to decompose seismic signals. Then, CEEMD is applied to extract instantaneous seismic attributes of 3D seismic data in a real-world coal mine in Inner Mongolia, China. The detection results demonstrate that instantaneous seismic attributes extracted by CEEMD are helpful to effectively identify the undulations of the top interfaces of limestone. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) refers to abnormal glucose tolerance, which is a common complication that occurs in some women for the first time during the gestation period. However, the relationship between onset of GDM and factors including advanced age and a family history of diabetes remains to be determined. The study aimed to examine the clinical significance of the detection of glycated albumin (GA) in pregnant women with GDM. A total of 893 cases of pregnant women with GDM were included, with 661 healthy pregnant women serving as the normal controls. A conditional logistic regression model was used to analyze the univariate and multivariate data to estimate the odds ratio (OR) and 95% confidence interval (95% CI). As the gestational weeks increased, the fasting blood glucose (FGP) concentration and GA-L value of the pregnant women in the normal control group gradually decreased whereas those of pregnant women with GDM greatly increased. The univariate analysis revealed that the impact factors on the occurrence of early-onset neonatal sepsis included, mother's age >35 years, complication of pregnancy hypertension, family history of hypertension, family history of diabetes, cesarean delivery, height, BMI, GA-L, and FGP. The multivariate logistic regression analysis revealed that the complication of pregnancy hypertension (OR=3.302; 95% CI, 1.705-6.394), family history of hypertension (OR=2.970; 95% CI, 1.520-5.801), GA-L (OR=1.556; 95% CI, 0.940-2.012) and FGP (OR=5.431; 95% CI, 4.097-7.198) were the main factors for pregnant women with GDM. In conclusion, pregnant women with GDM may be affected by various factors. Additionally, GA may be applied to reflect the recent blood glucose control on pregnant women with GDM. [ABSTRACT FROM AUTHOR]

Using air as the oxidant instead of the traditionally employed persulfates, the smaller and more uniform Pd nanoparticles (around 2 nm) supported on polyaniline (Pd@PANI) can be easily fabricated by the oxidation-polymerization of aniline with PdCl2. This material is an efficient and environmentally friendly catalyst for Heck reactions due to its recyclability, low loading, and ligand-free and mild reaction conditions. It was even tolerant to sulfur-containing substrates. This work reports the Pd@PANI-catalyzed Heck reactions with very wide substrate scopes, and discloses the catalytic mechanisms based on experimental findings and results of catalyst analysis and characterization. [ABSTRACT FROM AUTHOR]

Most scholars have recognized gated community as a new kind of negative and unacceptable defensive residential pattern in the context of globalization and neoliberal ideologies. However, widely different from the West, China's gated communities are mainly promoted by China's endogenous culture and social restructuring, which has also aggravated urban problems in recent years, such as spatial privatization, social segregation, residential discrimination, and traffic inaccessibility. According to some surveys and local experiences in China, the government reform of opening gated communities has actually failed since 2005. The objectives of this research therefore are to explain the paradox between maintaining culture and opposing policies, and the disputes between government, developers, residents, and experts relating to gated communities in China. By analyzing its evolution, characteristics, mechanism, and trend, the research finds that gating is represented as distinct symbols for various groups carrying different targets and values, and the solution to eliminate its negative influences is not to find an alternative residential pattern, but to make and implement new estate policies and design specifications. [ABSTRACT FROM AUTHOR]

The acoustic wave equation is an important basis for seismic wave propagation, imaging, and migration. This equation has led to the development of finite difference methods, but these methods are prone to numerical instability and grid dispersion problems, with the issue of dispersion being the most vital. Optimization methods can improve the accuracy across a large range of wavenumbers or frequencies. In this paper, we present a novel evolutionary optimization scheme for the acoustic wave equation. Our approach involves combining the fruit fly optimization algorithm (FOA) and sampling approximation (SA) to obtain the optimal difference operator for a wide range of wavenumbers. The difference coefficients are optimized to be extracted by the FOA, and the function of fitness, which is used to introduce an iterative process to determine the best smells, is evaluated by acoustic wave simulations. Based on the space-domain dispersion relation, we prove that the accuracy with which the absolute error is minimized is the same as that of the relative error. Within a given range of wavenumbers, we propose a fitness function by minimizing the absolute errors of the space-domain dispersion relation, and the dispersion analysis reveals that this scheme is superior to the Taylor-expansion scheme. We conduct two experiments by applying homogeneous and complex models, respectively. Further, the modeling results indicate that the fruit fly optimization approach in conjunction with sampling approximation preserve a higher accuracy for a small operator length and reduce the numerical artifacts. [ABSTRACT FROM AUTHOR]

In the present study, clonal amplifications of T-cell receptor β variable (TCR BV) linked to human cytomegalovirus (HCMV) infection were detected in recipients of allogeneic hematopoietic stem cell transplants (HSCT), and certain relationships between them were identified. Furthermore, the relationship between TCR BV sequences and HCMV infections was investigated. The results indicated that the 3 recipients of HSCT had monoclonal expansion of specific TCR BV clones following HSCT. Among these recipients, 2 suffered from pp65 and immediate early (IE) antigenemia. These patients demonstrated preferential expansion of TCR BV9 (QVRGGTDTQ) and TCR BV11 (VATDFQ). The remaining recipient did not express TCR BV9 and TCR BV11, nor did this individual have pp65 and IE antigenemia. These results suggest that expression of TCR BV9 and TCR BV11 may be associated with HCMV antigenemia, and may be involved in the immune response. The amino acid sequences ‘QVRGGTDTQ’ and ‘VATDFQ’ may be involved in HCMV reactivation in patients who have undergone HSCT. Assessment of the TCR BV families may provide valuable insight into HCMV pathogenesis and may aid in the diagnosis and therapy for HSCT recipients infected with HCMV. [ABSTRACT FROM AUTHOR]

Calcium dodecyl sulfate (CDS) was used for the first time both as an anionic surfactant and as the source of mineral ions in the precipitation process of calcium carbonate (CaCO3). The simple reaction of the enriched Ca2ions at the so-called organic-inorganic interfaces with the slowly bubbled CO2gas resulted in the metastable vaterite polymorph with various structures. The single-crystalline vaterite of the hexagonal platelets, the lens-shaped structures with hexagonal symmetry, the olive-shaped superstructures and these with a concave at each top of olives, and another metastable polymorph of aragonite were obtained, respectively, depending upon the concentration ratio between CDS and n-pentanol. The synergistic effect of CDS and n-pentanol is believed to play a crucial role in driving the oriented aggregation of metastable nanoparticles. Simultaneously, the novel phase transformation of vaterite to aragonite was observed, implying the possible formation mechanism of aragonite at room temperature and in the absence of magnesium ions. [ABSTRACT FROM AUTHOR]

The function of a metro station area is vital for city planners to consider when establishing a context-aware Transit-Oriented Development policy around the station area. However, the functions of metro station areas are hard to infer using the static land use distribution and other traditional survey datasets. In this paper, we propose a method to infer the functions occurring around the metro station catchment areas according to the patterns of staying activities derived from smart card data. We first define the staying activities by the spatial and temporal constraints of the two consecutive alighting and boarding records from the individual travel profile. Then we cluster and label the whole staying activities by considering the features of duration, frequency, and start time. By analyzing the percentage of different types of aggregated activities happening around each metro station, we cluster and explore the functions of the metro station area. Taking Wuhan as a case study, we analyze the results of Wuhan metro systems and discuss the similarities and differences between the functions and the land use distribution around the station area. The results show that although there exist some agreements, there is also a gap between the human activities and the land uses around the station area. These findings could give us deeper insight into how people act around the stations by metro systems, which will ultimately benefit the urban planning and policy development. [ABSTRACT FROM AUTHOR]

A molecular solution of an amphiphilic block copolymer may act as an oil phase by dispersing into an aqueous micellar system of small-molecular surfactant, forming oil-in-water (O/W) emulsion droplets. In this paper, an as-synthesized triblock copolymer poly(l-lactide)-polyoxyethylene-poly(l-lactide) (PLLA-PEO-PLLA) was dissolved in tetrahydrofuran (THF) and then added to an aqueous micellar solution of nonaethylene glycol monododecyl ether (AEO-9), forming initially coalescent O/W emulsion droplets in the size range of 35 nm-1.3 µm. Along with gradual volatilization of THF and simultaneous concentration of PLLA-PEO-PLLA molecules, the amphiphilic copolymer backbones themselves experience solution-based self-assembly, forming inverted core-corona aggregates within an oil-phase domain. Anisotropic coalescence of adjacent O/W emulsion droplets occurs, accompanied by further volatilization of THF. The hydrophilic block crystallization of core-forming PEOs and the hydrophobic chain stretch of corona-forming PLLAs together induce the intermediate formation of rod-like architectures with an average diameter of 300-800 nm, and this leads to a large-scale deposition of the triblock copolymer fibers with an average diameter of ~2.0 µm. Consequently, this strategy could be of general interest in the self-assembly formation of amphiphilic block copolymer fibers and could also provide access to aqueous solution crystallization of hydrophilic segments of these copolymers. [ABSTRACT FROM AUTHOR]

T-cell responses directed against human cytomegalovirus (HCMV) glycoprotein B (gB) contribute to protective immunity against HCMV infection in both animal models and humans. However, the gB-specific human CD8+ T cell responses remain poorly understood. gB antigen-specific CD8+ T cells were stained with seven major histocompatibility complex (MHC)-peptide pentamers in 16 human leukocyte antigen (HLA)-A*1101-positive, HCMV-seropositive patients following hematopoietic stem cell transplantation (HSCT). Of these seven pentamers, the most frequent CD8+ T-cell responses were directed against the gB332-340 peptide. These gB332-340-specific CD8+ T cells were strongly associated with the presence of plasma HCMV immunoglobulin M in all HSCT recipients and exhibited a probable causal relationship with the level of pp65 antigenemia. Together, these data suggest a role for gB332-340-specific CD8+ T cells in HCMV reactivation after HSCT. Furthermore, the pentamer assay may be valuable in detecting antigen-specific CD8+ T cells. [ABSTRACT FROM AUTHOR]

The fast mixing of aqueous solutions of calcium chloride and sodium carbonate could immediately result in amorphous calcium carbonate (ACC). Under vigorous stirring, the formed ACC in the precipitation system will dissolve first and, then, transform within minutes to produce crystalline forms of vaterite and calcite. After that, the solution-mediated mechanism dominates the transformation of the thermodynamically unstable vaterite into the thermodynamically stable calcite. Although ACC is the least stable form of the six anhydrous phases of calcium carbonate (CaCO3), it could be, however, produced and stabilized by a variety of organisms. To better understand the formation−transformation mechanism of ACC and vaterite into calcite, ex-situ methods (i.e., scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction spectroscopy) were used to characterize the formation−transformation process of ACC and vaterite in aqueous systems without organic additives, showing that ACC sampled at different conditions has different properties (i.e., lifetime, morphology, and spectrum characterization). It is also very interesting to capture the obviously polycrystalline particles of CaCO3 during the transformation process from vaterite to calcite, which suggests the formation mechanism for the calcite superstructure with multidimensional morphology. [ABSTRACT FROM AUTHOR]

In this paper a neural network for solving partial differential equations is described. The activation functions of the hidden nodes are the radial basis functions (RBF) whose parameters are learnt by a two-stage gradient descent strategy. A new growing RBF-node insertion strategy with different RBF is used in order to improve the net performances. The learning strategy is able to save computational time and memory space because of the selective growing of nodes whose activation functions consist of different RBFs. An analysis of the learning capabilities and a comparison of the net performances with other approaches have been performed. It is shown that the resulting network improves the approximation results. [Copyright &y& Elsevier]

Background: An important problem in selective attention is determining the ways the primary visual cortex contributes to the encoding of bottom-up saliency and the types of neural computation that are effective to model this process. To address this problem, we constructed a two-layered network that satisfies the neurobiological constraints of the primary visual cortex to detect salient objects. We carried out experiments on both synthetic images and natural images to explore the influences of different factors, such as network structure, the size of each layer, the type of suppression and the combination strategy, on saliency detection performance.Results: The experimental results statistically demonstrated that the type and scale of filters contribute greatly to the encoding of bottom-up saliency. These two factors correspond to the mechanisms of invariant encoding and overcomplete representation in the primary visual cortex.Conclusions: (1) Instead of constructing Gabor functions or Gaussian pyramids filters for feature extraction as traditional attention models do, we learn overcomplete basis sets from natural images to extract features for saliency detection. Experiments show that given the proper layer size and a robust combination strategy, the learned overcomplete basis set outperforms a complete set and Gabor pyramids in visual saliency detection. This finding can potentially be applied in task-dependent and supervised object detection. (2) A hierarchical coding model that can represent invariant features, is designed for the pre-attentive stage of bottom-up attention. This coding model improves robustness to noises and distractions and improves the ability of detecting salient structures, such as collinear and co-circular structures, and several composite stimuli. This result indicates that invariant representation contributes to saliency detection (popping out) in bottom-up attention. The aforementioned perspectives will significantly contribute to the in-depth understanding of the information processing mechanism in the primary visual system. [ABSTRACT FROM AUTHOR]