bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contract design on digital platform for the risk-averse retailer with moral hazard
Authors: Li Zhenhong , Li Bo , Lan Yanfei 
Published: December 2017

Purpose
The advent of e-commerce has prompted the proliferation of digital platforms for virtual products. This reinforces the importance of the contract design problem between the virtual product supplier (he) and the digital platform retailer (she). The purpose of this paper is to investigate a principal-agent problem in a virtual product supply chain, in which the retailer’s sales-effort investment level to sell the virtual product is unobservable to the supplier, and the market demand is unknown to both parties.

Design/methodology/approach
In this study, the supplier designs two kinds of contracts (wholesale price contract and two-part tariff contract) to maximize his profit, while the retailer determines her sales-effort investment level and the virtual product’s retail price. The results of two different types of contracts are compared to explore in depth the effect of contract choices on the participants’ profits.

Findings
The authors show that the comparative results of the optimal wholesale prices, retail prices and sales-effort investment levels between these two kinds of contracts all rely on the retailer’s risk-averse degree. Specifically, both the supplier and the whole supply chain prefer the two-part tariff contract rather than the wholesale price contract, the retailer should do opposite when she is low risk-averse, whereas there is no distinction for the retailer’s utilities between these two kinds of contracts when she is more risk-averse.

Originality/value
The value of the research rests on the use of principal-agent theory in the contracts of virtual products considering the retailer’s sales-effort and risk-aversion degree. The research will serve as a guide for the virtual products’ supplier and the platform retailer in decision-making processes.
Experimental evaluation of Arabic OCR systems
Authors: Alghamdi Mansoor , Teahan William 
Published: December 2017

Purpose
The aim of this paper is to experimentally evaluate the effectiveness of the state-of-the-art printed Arabic text recognition systems to determine open areas for future improvements. In addition, this paper proposes a standard protocol with a set of metrics for measuring the effectiveness of Arabic optical character recognition (OCR) systems to assist researchers in comparing different Arabic OCR approaches.

Design/methodology/approach
This paper describes an experiment to automatically evaluate four well-known Arabic OCR systems using a set of performance metrics. The evaluation experiment is conducted on a publicly available printed Arabic dataset comprising 240 text images with a variety of resolution levels, font types, font styles and font sizes.

Findings
The experimental results show that the field of character recognition for printed Arabic still requires further research to reach an efficient text recognition method for Arabic script.

Originality/value
To the best of the authors’ knowledge, this is the first work that provides a comprehensive automated evaluation of Arabic OCR systems with respect to the characteristics of Arabic script and, in addition, proposes an evaluation methodology that can be used as a benchmark by researchers and therefore will contribute significantly to the enhancement of the field of Arabic script recognition.
The missing link in training to detect deception and its implications for justice
Authors: Ryan Saskia , Sherretts Nicole , Willmott Dominic , Mojtahedi Dara , Baughman Benjamin M. 
Published: December 2017

PurposeThe purpose of this paper is to investigate the effect of response bias and target gender on detecting deception.Design/methodology/approachParticipants were randomly assigned to one of three experimental conditions: a stereotype condition (bogus training group), a tell-signs condition (empirically tested cues), and a control condition. Participants were required to decide whether eight targets were lying or telling the truth, based upon the information they had been given. Accuracy was measured via a correct or incorrect response to the stimuli. The data were then analyzed using a 2×2×3 mixed analysis of variance (ANOVA) to determine whether any main or interactional effects were present.FindingsResults revealed training condition had no significant effect on accuracy, nor was there a within-subject effect of gender. However, there was a significant main effect of accuracy in detecting truth or lies, and a significant interaction between target gender and detecting truth or lies.Research limitations/implicationsFuture research should seek a larger sample of participants with a more extensive training aspect developed into the study, as the brief training offered here may not be fully reflective of the extent and intensity of training which could be offered to professionals.Originality/valueWithin the criminal justice system, the need for increased accuracy in detecting deception is of critical importance; not only to detect whether a guilty individual is being deceitful, but also whether someone is making a false confession, both to improve community safety by detaining the correct perpetrator for the crime but also to maintain public trust in the justice system. The present research provides a fresh insight into the importance of training effects in detecting deception.
Condensed Tannins Affect Bacterial and Fungal Microbiomes and Mycotoxin Production during Ensiling and upon Aerobic Exposure
Authors: Peng Kai , Jin Long , Niu Yan D. , Huang Qianqian , McAllister Tim A. , Yang Hee Eun , Denise Hubert , Xu Zhongjun , Acharya Surya , Wang Shunxi , Wang Yuxi 
Published: December 2017

ABSTRACT

Purple prairie clover (PPC;
Dalea purpurea
Vent.) containing 84.5 g/kg dry matter (DM) of condensed tannin (CT) was ensiled without (control) or with polyethylene glycol (PEG) for 76 days, followed by 14 days of aerobic exposure. Changes in fermentation characteristics were determined, and the composition of bacterial and fungal communities were assessed using metagenomic sequencing. The addition of polyethylene glycol (PEG) that deactivated CT at ensiling increased (
P
< 0.05 to ∼0.001) soluble N, nonprotein N, lactic acid, total volatile fatty acids, ammonia N, deoxynivalenol (DON), and ochratoxin A (OTA) but decreased (
P
< 0.001) pH and water-soluble carbohydrates. The concentrations of DON and OTA increased (
P
< 0.001) for both silages, with the extent of increase being greater for control than for PEG-treated silage during aerobic exposure. The PEG-treated silage exhibited higher (
P
< 0.01 to ∼0.001) copy numbers of total bacteria,
Lactobacillus
, yeasts, and fungi than the control. The addition of PEG decreased (
P
< 0.01) bacterial diversity during both ensiling and aerobic exposure, whereas it increased (
P
< 0.05) fungal diversity during aerobic exposure. The addition of PEG at ensiling increased (
P
< 0.05) the abundances of
Lactobacillus
and
Pediococcus
species but decreased (
P
< 0.01) the abundances of
Lactococcus
and
Leuconostoc
species. Filamentous fungi were found in the microbiome at ensiling and after aerobic exposure, whereas
Bacillus
spp. were the dominate bacteria after aerobic exposure. In conclusion, CT decreased protein degradation and improved the aerobic stability of silage. These desirable outcomes likely reflect the ability of PPC CT to inhibit those microorganisms involved in lowering silage quality and in the production of mycotoxins.

IMPORTANCE
The present study reports the effects of condensed tannins on the complex microbial communities involved in ensiling and aerobic exposure of purple prairie clover. This study documents the ability of condensed tannins to lower mycotoxin production and the associated microbiome. Taxonomic bacterial community profiles were dominated by
Lactobacillales
after fermentation, with a notable increase in
Bacillus
spp. as a result of aerobic exposure. It is interesting to observe that condensed tannins decreased bacterial diversity during both ensiling and aerobic exposure but increased fungal diversity during aerobic exposure only. The present study indicates that the effects of condensed tannins on microbial communities lead to reduced lactic acid and total volatile fatty acid production, proteolysis, and mycotoxin concentration in the terminal silage and improved aerobic stability. Condensed tannins could be used as an additive to control unfavorable microbial development and maybe enhanced feed safety.
CCR2
+
Inflammatory Monocytes Are Recruited to Yersinia pseudotuberculosis Pyogranulomas and Dictate Adaptive Responses at the Expense of Innate Immunity during Oral Infection
Authors: Zhang Yue , Khairallah Camille , Sheridan Brian S. , van der Velden Adrianus W. M. , Bliska James B. 
Published: December 2017

ABSTRACT

Murine Ly6C
hi
inflammatory monocytes (IMs) require CCR2 to leave the bone marrow and enter mesenteric lymph nodes (MLNs) and other organs in response to
Yersinia pseudotuberculosis
infection. We are investigating how IMs, which can differentiate into CD11c
+
dendritic cells (DCs), contribute to innate and adaptive immunity to
Y. pseudotuberculosis
. Previously, we obtained evidence that IMs are important for a dominant CD8
+
T cell response to the epitope YopE
69–77
and host survival using intravenous infections with attenuated
Y. pseudotuberculosis
. Here we challenged CCR2
+/+
or CCR2
−/−
mice orally with wild-type
Y. pseudotuberculosis
to investigate how IMs contribute to immune responses during intestinal infection. Unexpectedly, CCR2
−/−
mice did not have reduced survival but retained body weight better and their MLNs cleared
Y. pseudotuberculosis
faster and with reduced lymphadenopathy compared to controls. Enhanced bacterial clearance in CCR2
−/−
mice correlated with reduced numbers of IMs in spleens and increased numbers of neutrophils in livers.
In situ
imaging of MLNs and spleens from CCR2-GFP mice showed that green fluorescent protein-positive (GFP
+
) IMs accumulated at the periphery of neutrophil-rich
Yersinia-
containing pyogranulomas. GFP
+
IMs colocalized with CD11c
+
cells and YopE
69–77
-specific CD8
+
T cells in MLNs, suggesting that IM-derived DCs prime adaptive responses in
Yersinia
pyogranulomas. Consistently, CCR2
−/−
mice had reduced numbers of splenic DCs, YopE
69–77
-specific CD8
+
T cells, CD4
+
T cells, and B cells in organs and lower levels of serum antibodies to
Y. pseudotuberculosis
antigens. Our data suggest that IMs differentiate into DCs in MLN pyogranulomas and direct adaptive responses in T cells at the expense of innate immunity during oral
Y. pseudotuberculosis
infection.
Dual Ligand Insertion in gB and gD of Oncolytic Herpes Simplex Viruses for Retargeting to a Producer Vero Cell Line and to Cancer Cells
Authors: Petrovic Biljana , Leoni Valerio , Gatta Valentina , Zaghini Anna , Vannini Andrea , Campadelli-Fiume Gabriella 
Published: December 2017

ABSTRACT

Oncolytic viruses gain cancer specificity in several ways. Like the majority of viruses, they grow better in cancer cells that are defective in mounting the host response to viruses. Often, they are attenuated by deletion or mutation of virulence genes that counteract the host response or are naturally occurring oncolytic mutants. In contrast, retargeted viruses are not attenuated or deleted; their cancer specificity rests on a modified, specific tropism for cancer receptors. For herpes simplex virus (HSV)-based oncolytics, the detargeting-retargeting strategies employed so far were based on genetic modifications of gD. Recently, we showed that even gH or gB can serve as retargeting tools. To enable the growth of retargeted HSVs in cells that can be used for clinical-grade virus production, a double-retargeting strategy has been developed. Here we show that several sites in the N terminus of gB are suitable to harbor the 20-amino-acid (aa)-long GCN4 peptide, which readdresses HSV tropism to Vero cells expressing the artificial GCN4 receptor and thus enables virus cultivation in the producer noncancer Vero-GCN4R cell line. The gB modifications can be combined with a minimal detargeting modification in gD, consisting in the deletion of two residues, aa 30 and 38, and replacement of aa 38 with the scFv to human epidermal growth factor receptor 2 (HER2), for retargeting to the cancer receptor. The panel of recombinants was analyzed comparatively in terms of virus growth, cell-to-cell spread, cytotoxicity, and
in vivo
antitumor efficacy to define the best double-retargeting strategy.

IMPORTANCE
There is increasing interest in oncolytic viruses, following FDA and the European Medicines Agency (EMA) approval of HSV Oncovex
GM-CSF
, and, mainly, because they greatly boost the immune response to the tumor and can be combined with immunotherapeutic agents, particularly checkpoint inhibitors. A strategy to gain cancer specificity and avoid virus attenuation is to retarget the virus tropism to cancer-specific receptors of choice. Cultivation of fully retargeted viruses is challenging, since they require cells that express the cancer receptor. We devised a strategy for their cultivation in producer noncancer Vero cell derivatives. Here, we developed a double-retargeting strategy, based on insertion of one ligand in gB for retargeting to a Vero cell derivative and of anti-HER2 ligand in gD for cancer retargeting. These modifications were combined with a minimally destructive detargeting strategy. This study and its companion paper explain the clinical-grade cultivation of retargeted oncolytic HSVs and promote their translation to the clinic.
Corneal perforation from peripheral ulcerative keratopathy in patients with rheumatoid arthritis: epidemiological findings of the British Ophthalmological Surveillance Unit
Authors: Timlin Hannah Mary , Hall Hildegard Nikki , Foot Barny , Koay Peter 
Published: December 2017

Background/AimsThis study quantifies the threat to vision and the survival in patients presenting with peripheral ulcerative keratopathy (PUK) corneal perforation associated with rheumatoid arthritis (RA) in the UK.MethodsNew cases of corneal perforation from PUK in patients with RA were prospectively collected from the UK via the British Ophthalmological Surveillance Unit from July 2012 to June 2014. An initial questionnaire collected data on presentation and the first 2 weeks’ management, and a follow-up questionnaire collected 1-year data on ocular morbidity and mortality.Results30 eyes of 28 patients were identified over 2 years, estimating a UK incidence of 0.234/million/year. 20/27 (74%) were female, with a median age of 68 years (range 41–84). The most common initial management was cyanoacrylate glue with a bandage contact lens, oral steroids, topical and oral antibiotics, and lubricants. Long-term management included corneal grafting in 12/20 (60%) eyes of patients living at 1 year. The 1-year all-cause mortality was 6/25 (24%), which increased to 1/2 (50%) if both eyes had perforated. In the remaining patients alive at 1-year follow-up, there was a 13/20 (65%) poor visual outcome of less than or equal to counting fingers. 8/25 (40%) patients had bilateral PUK, with 2/25 (8%) having bilateral perforation. 5/19 (26%) patients alive at 1-year follow-up were eligible for sight impairment registration.ConclusionThis study highlights the serious ocular morbidity and high mortality associated with corneal perforation from PUK in patients with RA despite treatment. The mortality doubled if both eyes perforated, which should serve as a harbinger of impending serious medical problems.
Intelligent Modeling for Nuclear Power Plant Accident Management
Authors: Darling Michael C. , Luger George F. , Jones Thomas B. , Denman Matthew R. , Groth Katrina M. 
Published: December 2017

This paper explores the viability of using counterfactual reasoning for impact analyses when understanding and responding to “beyond-design-basis” nuclear power plant accidents. Currently, when a severe nuclear power plant accident occurs, plant operators rely on Severe Accident Management Guidelines. However, the current guidelines are limited in scope and depth: for certain types of accidents, plant operators would have to work to mitigate the damage with limited experience and guidance for the particular situation. We aim to fill the need for comprehensive accident support by using a dynamic Bayesian network to aid in the diagnosis of a nuclear reactor's state and to analyze the impact of possible response measures. The dynamic Bayesian network, DBN, offers an expressive representation of the components and relationships that make up a complex causal system. For this reason, and for its tractable reasoning, the DBN supports a functional model for the intricate operations of nuclear power plants. In this domain, it is also pertinent that a Bayesian network can be composed of both probabilistic and knowledge-based components. Though probabilities can be calculated from simulated models, the structure of the network, as well as the value of some parameters, must be assigned by human experts. Since dynamic Bayesian network-based systems are capable of running better-than-real-time situation analyses, they can support both current event and alternate scenario impact analyses.
H3B-6527 Is a Potent and Selective Inhibitor of FGFR4 in FGF19-Driven Hepatocellular Carcinoma
Authors: Joshi Jaya Julie , Coffey Heather , Corcoran Erik , Tsai Jennifer , Huang Chia-Ling , Ichikawa Kana , Prajapati Sudeep , Hao Ming-Hong , Bailey Suzanna , Wu Jeremy , Rimkunas Victoria , Karr Craig , Subramanian Vanitha , Kumar Pavan , MacKenzie Crystal , Hurley Raelene , Satoh Takashi , Yu Kun , Park Eunice , Rioux Nathalie , Kim Amy , Lai Weidong G. , Yu Lihua , Zhu Ping , Buonamici Silvia , Larsen Nicholas , Fekkes Peter , Wang John , Warmuth Markus , Reynolds Dominic J. , Smith Peter G. , Selvaraj Anand 
Published: December 2017

Abstract
Activation of the fibroblast growth factor receptor FGFR4 by FGF19 drives hepatocellular carcinoma (HCC), a disease with few, if any, effective treatment options. While a number of pan-FGFR inhibitors are being clinically evaluated, their application to FGF19-driven HCC may be limited by dose-limiting toxicities mediated by FGFR1–3 receptors. To evade the potential limitations of pan-FGFR inhibitors, we generated H3B-6527, a highly selective covalent FGFR4 inhibitor, through structure-guided drug design. Studies in a panel of 40 HCC cell lines and 30 HCC PDX models showed that FGF19 expression is a predictive biomarker for H3B-6527 response. Moreover, coadministration of the CDK4/6 inhibitor palbociclib in combination with H3B-6527 could effectively trigger tumor regression in a xenograft model of HCC. Overall, our results offer preclinical proof of concept for H3B-6527 as a candidate therapeutic agent for HCC cases that exhibit increased expression of FGF19. Cancer Res; 77(24); 6999–7013. ©2017 AACR.
HSP27-Mediated Extracellular and Intracellular Signaling Pathways Synergistically Confer Chemoresistance in Squamous Cell Carcinoma of Tongue
Authors: Zheng Guopei , Zhang Zhijie , Liu Hao , Xiong Yan , Luo Liyun , Jia Xiaoting , Peng Cong , Zhang Qiong , Li Nan , Gu Yixue , Lu Minying , Song Ying , Pan Hao , Liu Jinbao , Liu Wanqing , He Zhimin 
Published: December 2017

Abstract
Purpose: Squamous cell carcinoma of tongue (SCCT) is the most common type of oral cavity carcinoma. Chemoresistance in SCCT is common, and the underlying mechanism remains largely unknown. We aimed to identify key molecules and signaling pathways mediating chemoresistance in SCCT.
Experimental Design: Using a proteomic approach, we found that the HSP27 was a potential mediator for chemoresistance in SCCT cells. To further validate this role of HSP27, we performed various mechanistic studies using in vitro and in vivo models as well as serum and tissue samples from SCCT patients.
Results: The HSP27 protein level was significantly increased in the multidrug-resistant SCCT cells and cell culture medium. Both HSP27 knockdown and anti-HSP27 antibody treatment reversed chemoresistance. Inversely, both HSP27 overexpression and recombinant human HSP27 protein treatment enhanced chemoresistance. Moreover, chemotherapy significantly induced HSP27 protein expression in both SCCT cells and their culture medium, as well as in tumor tissues and serum of SCCT patients. HSP27 overexpression predicts a poor outcome for SCCT patients receiving chemotherapy. Mechanically, extracellular HSP27 binds to TLR5 and then activates NF-κB signaling to maintain SCCT cell survival. TLR5 knockdown or restored IκBα protein level disrupts extracellular HSP27-induced NF-κB transactivation and chemoresistance. Moreover, intracellular HSP27 binds to BAX and BIM to repress their translocation to mitochondrion and subsequent cytochrome C release upon chemotherapy, resulting in inhibition of the mitochondrial apoptotic pathway.
Conclusions: HSP27 plays a pivotal role in chemoresistance of SCCT cells via a synergistic extracellular and intracellular signaling. HSP27 may represent a potential biomarker and therapeutic target for precision SCCT treatment. Clin Cancer Res; 24(5); 1163–75. ©2017 AACR.
Mitochondrial Inhibition Augments the Efficacy of Imatinib by Resetting the Metabolic Phenotype of Gastrointestinal Stromal Tumor
Authors: Vitiello Gerardo A. , Medina Benjamin D. , Zeng Shan , Bowler Timothy G. , Zhang Jennifer Q. , Loo Jennifer K. , Param Nesteene J. , Liu Mengyuan , Moral Alec J. , Zhao Julia N. , Rossi Ferdinand , Antonescu Cristina R. , Balachandran Vinod P. , Cross Justin R. , DeMatteo Ronald P. 
Published: December 2017

Abstract
Purpose: Imatinib dramatically reduces gastrointestinal stromal tumor (GIST) 18F-FDG uptake, providing an early indicator of treatment response. Despite decreased glucose internalization, many GIST cells persist, suggesting that alternative metabolic pathways are used for survival. The role of mitochondria in imatinib-treated GIST is largely unknown.
Experimental Design: We quantified the metabolic activity of several human GIST cell lines. We treated human GIST xenografts and genetically engineered KitV558del/+ mice with the mitochondrial oxidative phosphorylation inhibitor VLX600 in combination with imatinib and analyzed tumor volume, weight, histology, molecular signaling, and cell cycle activity. In vitro assays on human GIST cell lines were also performed.
Results: Imatinib therapy decreased glucose uptake and downstream glycolytic activity in GIST-T1 and HG129 cells by approximately half and upregulated mitochondrial enzymes and improved mitochondrial respiratory capacity. Mitochondrial inhibition with VLX600 had a direct antitumor effect in vitro while appearing to promote glycolysis through increased AKT signaling and glucose transporter expression. When combined with imatinib, VLX600 prevented imatinib-induced cell cycle escape and reduced p27 expression, leading to increased apoptosis when compared to imatinib alone. In KitV558del/+ mice, VLX600 alone did not induce tumor cell death, but had a profound antitumor effect when combined with imatinib.
Conclusions: Our findings show that imatinib alters the metabolic phenotype of GIST, and this may contribute to imatinib resistance. Our work offers preclinical proof of concept of metabolic targeting as an effective strategy for the treatment of GIST. Clin Cancer Res; 24(4); 972–84. ©2017 AACR.