Soft Methodology for Cost-and-error Sensitive Classification

Many real-world data mining applications need varying cost for different types of classification errors and thus call for cost-sensitive classification algorithms. Existing algorithms for cost-sensitive classification are successful in terms of minimizing the cost, but can result in a high error rate as the trade-off. The high error rate holds back the practical use of those algorithms. In this paper, we propose a novel cost-sensitive classification methodology that takes both the cost and the error rate into account. The methodology, called soft cost-sensitive classification, is established from a multicriteria optimization problem of the cost and the error rate, and can be viewed as regularizing cost-sensitive classification with the error rate. The simple methodology allows immediate improvements of existing cost-sensitive classification algorithms. Experiments on the benchmark and the real-world data sets show that our proposed methodology indeed achieves lower test error rates and similar (sometimes lower) test costs than existing cost-sensitive classification algorithms. We also demonstrate that the methodology can be extended for considering the weighted error rate instead of the original error rate. This extension is useful for tackling unbalanced classification problems.Comment: A shorter version appeared in KDD '1

Enzymatic Cross-Linking of Dynamic Thiol-Norbornene Click Hydrogels

Enzyme-mediated in situ forming hydrogels are attractive for many biomedical applications because gelation afforded by enzymatic reactions can be readily controlled not only by tuning macromer compositions, but also by adjusting enzyme kinetics. For example, horseradish peroxidase (HRP) has been used extensively for in situ cross-linking of macromers containing hydroxyl-phenol groups. The use of HRP to initiate thiol-allylether polymerization has also been reported, yet no prior study has demonstrated enzymatic initiation of thiol-norbornene gelation. In this study, we discovered that HRP can generate the thiyl radicals needed for initiating thiol-norbornene hydrogelation, which has only been demonstrated previously using photopolymerization. Enzymatic thiol-norbornene gelation not only overcomes light attenuation issue commonly observed in photopolymerized hydrogels, but also preserves modularity of the cross-linking. In particular, we prepared modular hydrogels from two sets of norbornene-modified macromers, 8-arm poly(ethylene glycol)-norbornene (PEG8NB) and gelatin-norbornene (GelNB). Bis-cysteine-containing peptides or PEG-tetra-thiol (PEG4SH) was used as a cross-linker for forming enzymatically and orthogonally polymerized hydrogel. For HRP-initiated PEG-peptide hydrogel cross-linking, gelation efficiency was significantly improved via adding tyrosine residues on the peptide cross-linkers. Interestingly, these additional tyrosine residues did not form permanent dityrosine cross-links following HRP-induced gelation. As a result, they remained available for tyrosinase-mediated secondary cross-linking, which dynamically increased hydrogel stiffness. In addition to material characterizations, we also found that both PEG- and gelatin-based hydrogels exhibited excellent cytocompatibility for dynamic 3D cell culture. The enzymatic thiol-norbornene gelation scheme presented here offers a new cross-linking mechanism for preparing modularly and dynamically cross-linked hydrogels

Improving gelation efficiency and cytocompatibility of visible light polymerized thiol-norbornene hydrogels via addition of soluble tyrosine

Hydrogels immobilized with biomimetic peptides have been used widely for tissue engineering and drug delivery applications. Photopolymerization has been among the most commonly used techniques to fabricate peptide-immobilized hydrogels as it offers rapid and robust peptide immobilization within a crosslinked hydrogel network. Both chain-growth and step-growth photopolymerizations can be used to immobilize peptides within covalently crosslinked hydrogels. A previously developed visible light mediated step-growth thiol-norbornene gelation scheme has demonstrated efficient crosslinking of hydrogels composed of an inert poly(ethylene glycol)-norbornene (PEGNB) macromer and a small molecular weight bis-thiol linker, such as dithiothreitol (DTT). Compared with conventional visible light mediated chain-polymerizations where multiple initiator components are required, step-growth photopolymerized thiol-norbornene hydrogels are more cytocompatible for the in situ encapsulation of radical sensitive cells (e.g., pancreatic β-cells). This contribution explored visible light based crosslinking of various bis-cysteine containing peptides with macromer 8-arm PEGNB to form biomimetic hydrogels suitable for in situ cell encapsulation. It was found that the addition of soluble tyrosine during polymerization not only significantly accelerated gelation, but also improved the crosslinking efficiency of PEG-peptide hydrogels as evidenced by a decreased gel point and enhanced gel modulus. In addition, soluble tyrosine drastically enhanced the cytocompatibility of the resulting PEG-peptide hydrogels, as demonstrated by in situ encapsulation and culture of pancreatic MIN6 β-cells. This visible light based thiol-norbornene crosslinking mechanism provides an attractive gelation method for preparing cytocompatible PEG-peptide hydrogels for tissue engineering applications

Biomimetic and enzyme-responsive dynamic hydrogels for studying cell-matrix interactions in pancreatic ductal adenocarcinoma

The tumor microenvironment (TME) governs all aspects of cancer progression and in vitro 3D cell culture platforms are increasingly developed to emulate the interactions between components of the stromal tissues and cancer cells. However, conventional cell culture platforms are inadequate in recapitulating the TME, which has complex compositions and dynamically changing matrix mechanics. In this study, we developed a dynamic gelatin-hyaluronic acid hybrid hydrogel system through integrating modular thiol-norbornene photopolymerization and enzyme-triggered on-demand matrix stiffening. In particular, gelatin was dually modified with norbornene and 4-hydroxyphenylacetic acid to render this bioactive protein photo-crosslinkable (through thiol-norbornene gelation) and responsive to tyrosinase-triggered on-demand stiffening (through HPA dimerization). In addition to the modified gelatin that provides basic cell adhesive motifs and protease cleavable sequences, hyaluronic acid (HA), an essential tumor matrix, was modularly and covalently incorporated into the cell-laden gel network. We systematically characterized macromer modification, gel crosslinking, as well as enzyme-triggered stiffening and degradation. We also evaluated the influence of matrix composition and dynamic stiffening on pancreatic ductal adenocarcinoma (PDAC) cell fate in 3D. We found that either HA-containing matrix or a dynamically stiffened microenvironment inhibited PDAC cell growth. Interestingly, these two factors synergistically induced cell phenotypic changes that resembled cell migration and/or invasion in 3D. Additional mRNA expression array analyses revealed changes unique to the presence of HA, to a stiffened microenvironment, or to the combination of both. Finally, we presented immunostaining and mRNA expression data to demonstrate that these irregular PDAC cell phenotypes were a result of matrix-induced epithelial-mesenchymal transition (EMT)

Inhibitory Effects of Resveratrol on PDGF-BB-Induced Retinal Pigment Epithelial Cell Migration via PDGFRβ, PI3K/Akt and MAPK Pathways

Purpose: In diseases such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, and age-related macular degeneration, retinal pigment epithelial (RPE) cells proliferate and migrate. Moreover, platelet-derived growth factor (PDGF) has been shown to enhance proliferation and migration of RPE cells in PVR. Even resveratrol can suppress the migration and adhesion of many cell types, its effects on RPE cell migration and adhesion remain unknown. In this study, we investigated the inhibitory effects of resveratrol on RPE cell migration induced by PDGF-BB, an isoform of PDGF, and adhesion to fibronectin, a major ECM component of PVR tissue. Methods: The migration of RPE cells was assessed by an electric cell-substrate impedance sensing migration assay and a Transwell migration assay. A cell viability assay was used to determine the viability of resveratrol treated-cells. The cell adhesion to fibronectin was examined by an adhesion assay. The interactions of resveratrol with PDGF-BB were analyzed by a dot binding assay. The PDGF-BB-induced signaling pathways were determined by western blotting and scratch wound healing assay. Results: Resveratrol inhibited PDGF-BB-induced RPE cell migration in a dose-dependent manner, but showed no effects on ARPE19 cell adhesion to fibronectin. The cell viability assay showed no cytotoxicity of resveratrol on RPE cells and the dot binding assay revealed no direct interactions of resveratrol with PDGF-BB. Inhibitory effects of resveratrol on PDGF-BB-induced platelet-derived growth factor receptor β (PDGFRβ) and tyrosine phosphorylation and the underlying pathways of PI3K/Akt, ERK and p38 activation were found; however, resveratrol and PDGF-BB showed no effects on PDGFRα and JNK activation. Scratch wound healing assay demonstrated resveratrol and the specific inhibitors of PDGFR, PI3K, MEK or p38 suppressed PDGF-BB-induced cell migration. Conclusions: These results indicate that resveratrol is an effective inhibitor of PDGF-BB-induced RPE cell migration via PDGFRβ, PI3K/Akt and MAPK pathways, but has no effects on the RPE cell adhesion to fibronectin

z ~ 4 Hα Emitters in the Great Observatories Origins Deep Survey: Tracing the Dominant Mode for Growth of Galaxies

We present evidence for strong Hα emission in galaxies with spectroscopic redshifts in the range of 3.8 10^(11) M_☉) galaxies at z ~ 3. This "strong Hα phase" of star formation plays a dominant role in galaxy growth at z ~ 4, and they are likely progenitors of massive red galaxies at lower redshifts

Remaining As A Leader or Not? Technology Spillover Answers

Much has been discussed about the advantages and disadvantages of being a first mover. However, discussion regarding the incentives encouraging a firm to remain as leader is absent in most studies. This paper aims to fill this gap and provide theoretical and empirical evidences vis-à-vis the incentives of remaining as a leader, by comparing profits between leader and follower when taking technology spillover and technological efficiency into consideration. The findings show that in regard to effective technological efficiency: (i) under the condition of a weak (strong) technology spillover, retaining the position of leader firm is (not) a dominant strategy because of higher (lower) profits than a follower; (ii) the half-shared technology spillover leads to an equal profit between firms, and implies a critical time of action for the leader firm to break the evenly-matched status by reconsidering first mover advantages; (iii) an empirical study on a data set of 352 high-tech and non-high-tech SMEs in manufacturing industry from 1999 until 2006 lends strong support to these results and may also provide useful clues for technology managers or practitioners to make better policies to benefit their market competitiveness