Surface-enhanced Raman scattering (SERS) has demonstrated single-molecule sensitivity and is becoming intensively investigated due to its significant potential in chemical and biomedical ...applications. SERS sensing is highly dependent on the substrate, where excitation of the localized surface plasmons (LSPs) enhances the Raman scattering signals of proximate analyte molecules. This paper reviews research progress of SERS substrates based on both plasmonic materials and nano-photonic structures. We first discuss basic plasmonic materials, such as metallic nanoparticles and nano-rods prepared by conventional bottom-up chemical synthesis processes. Then, we review rationally-designed plasmonic nano-structures created by top-down approaches or fine-controlled synthesis with high-density hot-spots to provide large SERS enhancement factors (EFs). Finally, we discuss the research progress of hybrid SERS substrates through the integration of plasmonic nano-structures with other nano-photonic devices, such as photonic crystals, bio-enabled nanomaterials, guided-wave systems, micro-fluidics and graphene.
In this study, we utilize a kernel theory of knowledge adoption model and propose a novel text analytic framework to classify the usefulness of solutions in online knowledge communities. The study ...combines multiple disciplines (behavioral, empirical, design science, and technical) to tackle an important and relevant business problem: how to effectively manage an online knowledge repository and identify useful solutions. Our framework can be implemented in online knowledge communities to improve users’ experience of searching for useful knowledge. The proposed framework has the potential to guide the development of customer-facing chatbots, which understand human-language questions and return helpful answers immediately.
Online communities and social collaborative platforms have become an increasingly popular avenue for knowledge sharing and exchange. In these communities, users often engage in informal conversations responding to questions and answers, and over time, they produce a huge amount of highly unstructured and implicit knowledge. How to effectively manage the knowledge repository and identify useful solutions thus becomes a major challenge. In this study, we propose a novel text analytic framework to extract important features from online forums and apply them to classify the usefulness of a solution. Guided by the design science research paradigm, we utilize a kernel theory of the knowledge adoption model, which captures a rich set of argument quality and source credibility features as the predictors of information usefulness. We test our framework on two large-scale knowledge communities: the Apple Support Community and Oracle Community. Our extensive analysis and performance evaluation illustrate that the proposed framework is both effective and efficient in predicting the usefulness of solutions embedded in the knowledge repository. We highlight the theoretical implications of the study as well as the practical applications of the framework to other domains.
Online consumer reviews can help customers reduce uncertainty and risks faced in online shopping. However, the studies examining the determinants of perceived review helpfulness produce mixed ...findings. We review extant research about the determinant factors of perceived online review helpfulness. All review related determinants (i.e., review depth, review readability, linear review rating, quadratic review rating, review age) and two reviewer related determinants (i.e., reviewer information disclosure and reviewer expertise) are found to have inconsistent conclusions on how they affect perceived review helpfulness. We conduct a meta-analysis to examine those determinant factors in order to reconcile the contradictory findings about their influence on perceived review helpfulness. The meta-analysis results affirm that review depth, review age, reviewer information disclosure, and reviewer expertise have positive influences on review helpfulness. Review readability and review rating are found to have no significant influence on review helpfulness. Moreover, we find that helpfulness measurement, online review platform, and product type are the three factors that cause mixed findings in extant research.
•We review extant research about the determinant factors of perceived online review helpfulness.•We conducted a meta-analysis to reconcile the contradictory findings on the influence of determinants on review helpfulness.•Helpfulness measurement, online review source, and product type are found to be responsible for most of the mixed findings.•Our findings help both sellers and consumers better identify helpful online reviews and improve the efficiency of decision-making.
Activating mutations in KRAS are among the most frequent events in diverse human carcinomas and are particularly prominent in human pancreatic ductal adenocarcinoma (PDAC). An inducible ...KrasG12D-driven mouse model of PDAC has established a critical role for sustained KrasG12D expression in tumor maintenance, providing a model to determine the potential for and the underlying mechanisms of KrasG12D–independent PDAC recurrence. Here, we show that some tumors undergo spontaneous relapse and are devoid of KrasG12D expression and downstream canonical MAPK signaling and instead acquire amplification and overexpression of the transcriptional coactivator Yap1. Functional studies established the role of Yap1 and the transcriptional factor Tead2 in driving KrasG12D-independent tumor maintenance. The Yap1/Tead2 complex acts cooperatively with E2F transcription factors to activate a cell cycle and DNA replication program. Our studies, along with corroborating evidence from human PDAC models, portend a novel mechanism of escape from oncogenic Kras addiction in PDAC.
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•Spontaneous tumor recurs following oncogenic Kras extinction-induced tumor regression•Yap1 amplification drives Kras-independent tumor relapse in Tead2-dependent manner•Yap1/Tead2 cooperate with E2F in promoting a cell-cycle gene expression program•Most Kras-independent tumors resemble the quasimesenchymal subtype of human PDAC
In a mouse model of pancreatic cancer, amplification of Yap1 allows tumor cells to escape addiction to oncogenic Kras
Penile squamous cell carcinoma (PSCC) accounts for over 95% of penile malignancies and causes significant mortality and morbidity in developing countries. Molecular mechanisms and therapies of PSCC ...are understudied, owing to scarcity of laboratory models. Herein, we describe a genetically engineered mouse model of PSCC, by co-deletion of Smad4 and Apc in the androgen-responsive epithelium of the penis. Mouse PSCC fosters an immunosuppressive microenvironment with myeloid-derived suppressor cells (MDSCs) as a dominant population. Preclinical trials in the model demonstrate synergistic efficacy of immune checkpoint blockade with the MDSC-diminishing drugs cabozantinib or celecoxib. A critical clinical problem of PSCC is chemoresistance to cisplatin, which is induced by Pten deficiency on the backdrop of Smad4/Apc co-deletion. Drug screen studies informed by targeted proteomics identify a few potential therapeutic strategies for PSCC. Our studies have established what we believe to be essential resources for studying PSCC biology and developing therapeutic strategies.
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•A microfluidic analytical device based on photonic crystal biosilica micro-channel array.•Ultra-high sensitivity for illicit drug sensing down to 1–10 ppb in human ...plasma.•Cost-effective platform for point-of-care applications.
The escalating research interests in porous media microfluidics, such as microfluidic paper-based analytical devices, have fostered a new spectrum of biomedical devices for point-of-care (POC) diagnosis and biosensing. In this paper, we report microfluidic diatomite analytical devices (μDADs), which consist of highly porous photonic crystal biosilica channels, as an innovative lab-on-a-chip platform to detect illicit drugs. The μDADs in this work are fabricated by spin-coating and tape-stripping diatomaceous earth on regular glass slides with cross section of 400 × 30 μm2. As the most unique feature, our μDADs can simultaneously perform on-chip chromatography to separate small molecules from complex biofluidic samples and acquire the surface-enhanced Raman scattering spectra of the target chemicals with high specificity. Owing to the ultra-small dimension of the diatomite microfluidic channels and the photonic crystal effect from the fossilized diatom frustules, we demonstrate unprecedented sensitivity down to part-per-billion (ppb) level when detecting pyrene (1ppb) from mixed sample with Raman dye and cocaine (10 ppb) from human plasma. This pioneering work proves the exclusive advantage of μDADs as emerging microfluidic devices for chemical and biomedical sensing, especially for POC drug screening.
Owing to a lack of response to the anti-PD1 therapy for most cancer patients, we develop a network approach to infer genes, pathways, and potential therapeutic combinations that are associated with ...tumor response to anti-PD1. Here, our prediction identifies genes and pathways known to be associated with anti-PD1, and is further validated by 6 CRISPR gene sets associated with tumor resistance to cytotoxic T cells and targets of the 36 compounds that have been tested in clinical trials for combination treatments with anti-PD1. Integration of our top prediction and TCGA data identifies hundreds of genes whose expression and genetic alterations that could affect response to anti-PD1 in each TCGA cancer type, and the comparison of these genes across cancer types reveals that the tumor immunoregulation associated with response to anti-PD1 would be tissue-specific. In addition, the integration identifies the gene signature to calculate the MHC I association immunoscore (MIAS) that shows a good correlation with patient response to anti-PD1 for 411 melanoma samples complied from 6 cohorts. Furthermore, mapping drug target data to the top genes in our association prediction identifies inhibitors that could potentially enhance tumor response to anti-PD1, such as inhibitors of the encoded proteins of CDK4, GSK3B, and PTK2.
Recently discovered extraordinary optical nonlinearities in epsilon-near-zero (ENZ) materials open a new realm of ultra-energy-efficient, all-optical switching devices for future optical ...communication and computation. In this paper, we propose a sub-micron, sub-pico-second, femto-joule level all-optical switch (AOS) using hybrid plasmonic-silicon waveguides driven by high mobility transparent conductive oxides (HMTCOs) such as cadmium oxide. Our analysis indicates that the ENZ-induced nonlinear optical effect is greatly enhanced by the high free carrier mobility in the telecom wavelength region. We propose an electrically tunable AOS device which is precisely biased at the ENZ condition, or the high-loss "OFF" state. Then the AOS device can be switched to the "ON" state with an unprecedented modulation strength of 15.9 dB/μm and a rapid switching time of 230 fs at the cost of an ultralow switching energy of 13.5 fJ. By defining a comprehensive metric using the product of device size, switching energy and switching time, the proposed ENZ-enabled device shows superior performance than any existing on-chip AOS device. We envision that such HMTCO-driven AOS device can be integrated with silicon photonic integrated circuits to realize on-chip optical signal processing and computation with ultra-low energy and ultra-high bandwidth.
A pressing need of vehicle quality management professionals is decision support for the vehicle defect discovery and classification process. In this paper, we employ text mining on a popular social ...medium used by vehicle enthusiasts: online discussion forums. We find that sentiment analysis, a conventional technique for consumer complaint detection, is insufficient for finding, categorizing, and prioritizing vehicle defects discussed in online forums, and we describe and evaluate a new process and decision support system for automotive defect identification and prioritization. Our findings provide managerial insights into how social media analytics can improve automotive quality management.
► Online auto enthusiast forums contain many postings relating to vehicle defects. ► Therefore, social media analytics for vehicle quality management should be explored. ► We find that sentiment analysis is not effective for identifying vehicle defects. ► We propose a novel Vehicle Defect Discovery System (VDDS) using text mining. ► Results show robust defect classification across multiple vehicle brands.
The biological functions and mechanisms of oncogenic KRASG12D (KRAS∗) in resistance to immune checkpoint blockade (ICB) therapy are not fully understood. We demonstrate that KRAS∗ represses the ...expression of interferon regulatory factor 2 (IRF2), which in turn directly represses CXCL3 expression. KRAS∗-mediated repression of IRF2 results in high expression of CXCL3, which binds to CXCR2 on myeloid-derived suppressor cells and promotes their migration to the tumor microenvironment. Anti-PD-1 resistance of KRAS∗-expressing tumors can be overcome by enforced IRF2 expression or by inhibition of CXCR2. Colorectal cancer (CRC) showing higher IRF2 expression exhibited increased responsiveness to anti-PD-1 therapy. The KRAS∗-IRF2-CXCL3-CXCR2 axis provides a framework for patient selection and combination therapies to enhance the effectiveness of ICB therapy in CRC.
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•Oncogenic KRAS promotes an immune-suppressive profile in CRC•IRF2 is a key downstream target of oncogenic KRAS-mediating immune suppression•IRF2 suppresses MDSC migration and infiltration by targeting the CXCL3-CXCR2 axis•Enforced IRF2 expression or CXCR2 inhibition overcomes anti-PD1 resistance in CRC
Liao et al. show that oncogenic KRAS represses IRF2 expression leading to high expression of CXCL3, which binds CXCR2 on MDSCs to promote their migration into the tumor microenvironment. Enforced IRF2 expression or CXCR2 blockade overcomes resistance of tumors expressing oncogenic KRAS to anti-PD-1 therapy.
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