Margin-based classifiers have been popular in both machine learning and statistics for classification problems. Among numerous classifiers, some are hard classifiers while some are soft ones. Soft ...classifiers explicitly estimate the class conditional probabilities and then perform classification based on estimated probabilities. In contrast, hard classifiers directly target the classification decision boundary without producing the probability estimation. These two types of classifiers are based on different philosophies and each has its own merits. In this article, we propose a novel family of large-margin classifiers, namely large-margin unified machines (LUMs), which covers a broad range of margin-based classifiers including both hard and soft ones. By offering a natural bridge from soft to hard classification, the LUM provides a unified algorithm to fit various classifiers and hence a convenient platform to compare hard and soft classification. Both theoretical consistency and numerical performance of LUMs are explored. Our numerical study sheds some light on the choice between hard and soft classifiers in various classification problems.
Hepatocellular carcinoma (HCC) is one of the most prevalent and fatal digestive tumors. Treatment for this disease has been constraint by heterogeneity of this group of tumors, which has greatly ...limited the progress in personalized therapy. Although existing studies have revealed the genetic and epigenetic blueprints that drive HCCs, many of the molecular mechanisms that lead to HCCs remain elusive. Recent advances in techniques for studying functional genomics, such as genome sequencing and transcriptomic analyses, have led to the discovery of molecular mechanisms that participate in the initiation and evolution of HCC. Integrative multi‐omics analyses have identified several molecular subtypes of HCC associated with specific molecular characteristics and clinical outcomes. Deciphering similar molecular features among highly heterogeneous HCC patients is a prerequisite to implementation of personalized therapeutics. This review summarizes the current research progresses in precision therapy on the backbone of molecular subtypes of HCC.
Abstract
Reversing the thermal induced sintering phenomenon and forming high temperature stable fine dispersed metallic centers with unique structural and electronic properties is one of the ...ever-lasting targets of heterogeneous catalysis. Here we report that the dispersion of metallic Ni particles into under-coordinated two-dimensional Ni clusters over γ-Mo
2
N is a thermodynamically favorable process based on the AIMD simulation. A Ni-4nm/γ-Mo
2
N model catalyst is synthesized and used to further study the reverse sintering effect by the combination of multiple in-situ characterization methods, including in-situ quick XANES and EXAFS, ambient pressure XPS and environmental SE/STEM etc. The under-coordinated two-dimensional layered Ni clusters on molybdenum nitride support generated from the Ni-4nm/γ-Mo
2
N has been demonstrated to be a thermally stable catalyst in 50 h stability test in CO
2
hydrogenation, and exhibits a remarkable catalytic selectivity reverse compared with traditional Ni particles-based catalyst, leading to a chemo-specific CO
2
hydrogenation to CO.
Manure application and sewage irrigation release many intestinal pathogens into the soil. After being introduced into the soil matrix, pathogens are commonly found to attach to soil minerals. ...Although the survival of mineral-associated Escherichia coli O157:H7 has been studied, a comprehensive understanding of the attachment process and physiological properties after attachment is still lacking.
In this study, planktonic and attached Escherichia coli O157:H7 cells on quartz were investigated using RNA sequencing (RNA-seq) and the isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic method. Based on the transcriptomic and proteomic analyses and gene knockouts, functional two-component system pathways were required for efficient attachment; chemotaxis and the Rcs system were identified to play determinant roles in E. coli O157:H7 attachment on quartz. After attachment, the pyruvate catabolic pathway shifted from the tricarboxylic acid (TCA) cycle toward the fermentative route. The survival rate of attached E. coli O157:H7 increased more than 10-fold under penicillin and vancomycin stress and doubled under alkaline pH and ferric iron stress.
These results contribute to the understanding of the roles of chemotaxis and the Rcs system in the attachment process of pathogens and indicate that the attachment of pathogens to minerals significantly elevates their resistance to antibiotics and environmental stress, which may pose a potential threat to public health.
Estimation of longitudinal data covariance structure poses significant challenges because the data usually are collected at irregular time points. A viable semiparametric model for covariance ...matrixes has been proposed that allows one to estimate the variance function nonparametrically and to estimate the correlation function parametrically by aggregating information from irregular and sparse data points within each subject. But the asymptotic properties of the quasi-maximum likelihood estimator (QMLE) of parameters in the covariance model are largely unknown. We address this problem in the context of more general models for the conditional mean function, including parametric, nonparametric, or semiparametric. We also consider the possibility of rough mean regression function and introduce the difference-based method to reduce biases in the context of varying-coefficient partially linear mean regression models. This provides a more robust estimator of the covariance function under a wider range of situations. Under some technical conditions, consistency and asymptotic normality are obtained for the QMLE of the parameters in the correlation function. Simulation studies and a real data example are used to illustrate the proposed approach.
Bioaugmentation has been frequently proposed in wastewater and soil treatment to remove toxic aromatic compounds. The performance of bioaugmentation is affected by a number of biological and ...environmental factors, including the interaction between the target pollutant and the augmented bacterial cells. In this study, using Comamonas testosteroni and 3-chloroaniline (3-CA) as the model organism and target pollutant, we explored the influence of toxic aromatic pollutants on the biofilm lifestyle of bacteria capable of degrading aromatic compounds toward a better understanding of cell-pollutant interaction in bioaugmentation. Our results showed that the exposure to 3-CA greatly reduced the retention of C. testosteroni cells in packed-bed bioreactors (from 22% to 15% after three pore volumes), which could be attributed to the altered bacterial motility and cell surface hydrophobicity. To further understand the molecular mechanisms, we employed an integrated genomic and transcriptomic analysis to examine the influence of 3-CA on the expression of genes important to the biofilm lifestyle of C. testosteroni We found that exposure to 3-CA reduced the intracellular c-di-GMP level by downregulating the expression of genes encoding c-di-GMP synthases and induced massive cell dispersal from the biofilms. Our findings provide novel environmental implications on bioaugmentation, particularly in biofilm reactors, for the treatment of wastewater containing recalcitrant industrial pollutants.
Bioaugmentation is a bioremediation approach that often has been described in the literature but has almost never been successfully applied in practice. Many biological and environmental factors influence the overall performance of bioaugmentation. Among these, the interaction between the target pollutant and the augmented bacterial cells is one of the most important factors. In this study, we revealed the influence of toxic aromatic pollutants on the biofilm lifestyle of bacteria capable of degrading aromatic compounds toward a better understanding of cell-pollutant interaction in bioaugmentation. Our findings provide novel environmental implications on bioaugmentation for the treatment of wastewater containing recalcitrant industrial pollutants; in particular, the exposure to toxic pollutants may reduce the retention of augmented organisms in biofilm reactors by reducing the c-di-GMP level, and approaches to elevating or maintaining a high c-di-GMP level may be promising to establish and maintain sustainable bioaugmentation activity.
This study focuses on an investigation of the operating performance and pollutant emission characteristics of a micro gas turbine combined cycle using biomass gas, replacing natural gas. The models ...of both recuperative cycle micro gas turbines with a waste heat utilization system and a micro gas-steam turbine combined cycle system are established. When the gas turbine works at 100 kW and the same types of fuel are burnt, the recuperative cycle system consumes less fuel than the gas-steam combined cycle system. The electric efficiency of the recuperative cycle system can reach more than 29%, which is higher than 24% of the gas-steam combined system. The combined cycle thermal efficiency of the recuperative system is as high as 66%, with 36% waste heat utilization efficiency. The electrical efficiency of the recuperative cycle system in the biomass gas case decreases, while that of the gas-steam combined cycle system undergoes little change. When the gas turbine power output increases from 50 kW to 100 kW, the electrical efficiency and combined cycle thermal efficiency increases, but the thermal efficiency of waste heat utilization of recuperative cycle decreases, the NOX and SO2 emissions gradually rise. Under the same working conditions, the NOX emissions of the recuperative cycle system are greater than that of the steam-gas combined cycle system.
Traditionally, chronic wound infection is diagnosed by visual inspection under white light and microbiological sampling, which are subjective and suboptimal, respectively, thereby delaying diagnosis ...and treatment. To address this, we developed a novel handheld, fluorescence imaging device (PRODIGI) that enables non-contact, real-time, high-resolution visualization and differentiation of key pathogenic bacteria through their endogenous autofluorescence, as well as connective tissues in wounds.
This was a two-part Phase I, single center, non-randomized trial of chronic wound patients (male and female, ≥18 years; UHN REB #09-0015-A for part 1; UHN REB #12-5003 for part 2; clinicaltrials.gov Identifier: NCT01378728 for part 1 and NCT01651845 for part 2). Part 1 (28 patients; 54% diabetic foot ulcers, 46% non-diabetic wounds) established the feasibility of autofluorescence imaging to accurately guide wound sampling, validated against blinded, gold standard swab-based microbiology. Part 2 (12 patients; 83.3% diabetic foot ulcers, 16.7% non-diabetic wounds) established the feasibility of autofluorescence imaging to guide wound treatment and quantitatively assess treatment response. We showed that PRODIGI can be used to guide and improve microbiological sampling and debridement of wounds in situ, enabling diagnosis, treatment guidance and response assessment in patients with chronic wounds. PRODIGI is safe, easy to use and integrates into the clinical workflow. Clinically significant bacterial burden can be detected in seconds, quantitatively tracked over days-to-months and their biodistribution mapped within the wound bed, periphery, and other remote areas.
PRODIGI represents a technological advancement in wound sampling and treatment guidance for clinical wound care at the point-of-care.
ClinicalTrials.gov NCT01651845; ClinicalTrials.gov NCT01378728.
The development of metastases involves the dissociation of cells from the primary tumor to penetrate the basement membrane, invade and then exit the vasculature to seed, and colonize distant tissues. ...The last step, establishment of macroscopic tumors at distant sites, is the least well understood. Four isogenic mouse breast cancer cell lines (67NR, 168FARN, 4TO7, and 4T1) that differ in their ability to metastasize when implanted into the mammary fat pad are used to model the steps of metastasis. Only 4T1 forms macroscopic lung and liver metastases. Because some miRNAs are dysregulated in cancer and affect cellular transformation, tumor formation, and metastasis, we examined whether changes in miRNA expression might explain the differences in metastasis of these cells.
miRNA expression was analyzed by miRNA microarray and quantitative RT-PCR in isogenic mouse breast cancer cells with distinct metastatic capabilities. 4T1 cells that form macroscopic metastases had elevated expression of miR-200 family miRNAs compared to related cells that invade distant tissues, but are unable to colonize. Moreover, over-expressing miR-200 in 4TO7 cells enabled them to metastasize to lung and liver. These findings are surprising since the miR-200 family was previously shown to promote epithelial characteristics by inhibiting the transcriptional repressor Zeb2 and thereby enhancing E-cadherin expression. We confirmed these findings in these cells. The most metastatic 4T1 cells acquired epithelial properties (high expression of E-cadherin and cytokeratin-18) compared to the less metastatic cells.
Expression of miR-200, which promotes a mesenchymal to epithelial cell transition (MET) by inhibiting Zeb2 expression, unexpectedly enhances macroscopic metastases in mouse breast cancer cell lines. These results suggest that for some tumors, tumor colonization at metastatic sites might be enhanced by MET. Therefore the epithelial nature of a tumor does not predict metastatic outcome.
PDF
