bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exacerbation of Collagen Antibody–Induced Arthritis in Transgenic Mice Overexpressing Peroxiredoxin 6
Authors: Kim Dae Hwan , Lee Dong Hun , Jo Mi Ran , Son Dong Ju , Park Mi Hee , Hwang Chul Ju , Park Ju Ho , Yuk Dong Yeon , Yoon Do Young , Jung Young‐Suk , Kim Youngsoo , Jeong Jae Hwang , Han Sang Bae , Hong Jin Tae 
Published: July 2015

ObjectivePeroxiredoxin 6 plays important and complex roles in the process of inflammation, but its role in the development of rheumatoid arthritis (RA) remains unclear. We undertook this study to investigate the roles and mechanisms of peroxiredoxin 6 in the development of collagen antibody–induced arthritis (CAIA) and antigen‐induced arthritis (AIA) in peroxiredoxin 6–overexpressing transgenic mice, in peroxiredoxin 6–transfected RAW 264.7 cells, in macrophages isolated from peroxiredoxin 6–overexpressing transgenic mice, and in synoviocytes from arthritis patients.MethodsCAIA and AIA were induced using standard methods. Peroxiredoxin 6–transfected RAW 264.7 cells, macrophages isolated from peroxiredoxin 6–overexpressing transgenic mice, and synoviocytes from arthritis patients were used to study proinflammatory responses and mechanisms. Clinical scores and histopathologic changes were determined in peroxiredoxin 6–overexpressing transgenic mice and wild‐type (WT) mice with CAIA or AIA. Generation of nitric oxide (NO), expression of inducible NO synthase and cyclooxygenase 2, and activity of NF‐κB and activator protein 1 (AP‐1) were determined in cultured macrophages and synoviocytes as well as in joint tissue from mice by Western blotting, electrophoretic mobility shift assay, and immunohistochemical analysis.ResultsDevelopment of CAIA and AIA and proinflammatory responses were more exacerbated in peroxiredoxin 6–overexpressing transgenic mice than in WT mice. Overexpression of peroxiredoxin 6 increased lipopolysaccharide‐induced inflammatory responses in RAW 264.7 cells, in macrophages isolated from peroxiredoxin 6–overexpressing transgenic mice, and in synoviocytes from arthritis patients, and this was accompanied by up‐regulation of the JNK pathway. Moreover, a JNK inhibitor completely blocked RA development and proinflammatory responses.ConclusionOur findings suggest that overexpression of peroxiredoxin 6 might promote development of RA through NF‐κB and AP‐1 activity via the JNK pathway.
Viral vaccines and their manufacturing cell substrates: New trends and designs in modern vaccinology
Authors: Rodrigues Ana F. , Soares Hugo R. , Guerreiro Miguel R. , Alves Paula M. , Coroadinha Ana S. 
Published: July 2015

AbstractVaccination is one of the most effective interventions in global health. The worldwide vaccination programs significantly reduced the number of deaths caused by infectious agents. A successful example was the eradication of smallpox in 1979 after two centuries of vaccination campaigns. Since the first variolation administrations until today, the knowledge on immunology has increased substantially. This knowledge combined with the introduction of cell culture and DNA recombinant technologies revolutionized vaccine design. This review will focus on vaccines against human viral pathogens, recent developments on vaccine design and cell substrates used for their manufacture. While the production of attenuated and inactivated vaccines requires the use of the respective permissible cell substrates, the production of recombinant antigens, virus‐like particles, vectored vaccines and chimeric vaccines requires the use – and often the development – of specific cell lines. Indeed, the development of novel modern viral vaccine designs combined with, the stringent safety requirements for manufacture, and the better understanding on animal cell metabolism and physiology are increasing the awareness on the importance of cell line development and engineering areas. A new era of modern vaccinology is arriving, offering an extensive toolbox to materialize novel and creative ideas in vaccine design and its manufacture.
Current progress in high cell density yeast bioprocesses for bioethanol production
Authors: Westman Johan O. , Franzén Carl Johan 
Published: July 2015

AbstractHigh capital costs and low reaction rates are major challenges for establishment of fermentation‐based production systems in the bioeconomy. Using high cell density cultures is an efficient way to increase the volumetric productivity of fermentation processes, thereby enabling faster and more robust processes and use of smaller reactors. In this review, we summarize recent progress in the application of high cell density yeast bioprocesses for first and second generation bioethanol production. High biomass concentrations obtained by retention of yeast cells in the reactor enables easier cell reuse, simplified product recovery and higher dilution rates in continuous processes. High local cell density cultures, in the form of encapsulated or strongly flocculating yeast, furthermore obtain increased tolerance to convertible fermentation inhibitors and utilize glucose and other sugars simultaneously, thereby overcoming two additional hurdles for second generation bioethanol production. These effects are caused by local concentration gradients due to diffusion limitations and conversion of inhibitors and sugars by the cells, which lead to low local concentrations of inhibitors and glucose. Quorum sensing may also contribute to the increased stress tolerance. Recent developments indicate that high cell density methodology, with emphasis on high local cell density, offers significant advantages for sustainable second generation bioethanol production.
A global RNA‐seq‐driven analysis of CHO host and production cell lines reveals distinct differential expression patterns of genes contributing to recombinant antibody glycosylation
Authors: Könitzer Jennifer D. , Müller Markus M. , Leparc Germán , Pauers Martin , Bechmann Jan , Schulz Patrick , Schaub Jochen , Enenkel Barbara , Hildebrandt Tobias , Hampel Martin , Tolstrup Anne B. 
Published: July 2015

AbstractBoehringer Ingelheim uses two CHO‐DG44 lines for manufacturing biotherapeutics, BI‐HEX‐1 and BI‐HEX‐2, which produce distinct cell type‐specific antibody glycosylation patterns. A recently established CHO‐K1 descended host, BI‐HEX‐K1, generates antibodies with glycosylation profiles differing from CHO‐DG44. Manufacturing process development is significantly influenced by these unique profiles. To investigate the underlying glycosylation related gene expression, we leveraged our CHO host and production cell RNA‐seqtranscriptomics and product quality database together with the CHO‐K1 genome. We observed that each BI‐HEX host and antibody producing cell line has a unique gene expression fingerprint. CHO‐DG44 cells only transcribe Fut10, Gfpt2 and ST8Sia6 when expressing antibodies. BI‐HEX‐K1 cells express ST8Sia6 at host cell level. We detected a link between BI‐HEX‐1/BI‐HEX‐2 antibody galactosylation and mannosylation and the gene expression of the B4galt gene family and genes controlling mannose processing. Furthermore, we found major differences between the CHO‐DG44 and CHO‐K1 lineages in the expression of sialyl transferases and enzymes synthesizing sialic acid precursors, providing a rationale for the lack of immunogenic NeuGc/NGNA synthesis in CHO. Our study highlights the value of systems biotechnology to understand glycoprotein synthesis and product glycoprofiles. Such data improve future production clone selection and process development strategies for better steering of biotherapeutic product quality.
Association of BMI with overall survival in patients with mCRC who received chemotherapy versus EGFR and VEGF‐targeted therapies
Authors: Patel Gargi S. , Ullah Shahid , Beeke Carol , Hakendorf Paul , Padbury Robert , Price Timothy J. , Karapetis Christos S. 
Published: July 2015

AbstractAlthough a raised body mass index (BMI) is associated with increased risk of colorectal cancer (CRC) and recurrence after adjuvant treatment, data in the metastatic setting is limited. We compared overall survival (OS) across BMI groups for metastatic CRC, and specifically examined the effect of BMI within the group of patients treated with targeted therapies (TT). Retrospective data were obtained from the South Australian Registry for mCRC from February 2006 to October 2012. The BMI at first treatment was grouped as underweight <18.5 kg/m2, Normal = 18.5 to <25 kg/m2, Overweight = 25 to <30 kg/m2, Obese I = 30 to <35 kg/m2, Obese II ≥35 kg/m2. Of 1174 patients, 42 were underweight, 462 overweight, 175 Obese I, and 77 Obese II. The OS was shorter for patients who were underweight and overweight compared to normal (OS 13.7 and 22.3 vs. 24.1 months, respectively, hazard ratio [HR] 2.21 and 1.23). The adjusted median OS was longer for normal versus overweight or obese I patients receiving chemotherapy + targeted therapy (35.7 vs 25.1 or 22.8 months, HR 1.59 and 1.63, respectively) with no difference in OS for chemotherapy alone. On breakdown by type of targeted therapy, overweight and obese I patients had a poorer outcome with Bevacizumab. The BMI is predictive of a poorer outcome for underweight and overweight patients in the whole population. Of those receiving chemotherapy and targeted therapy, BMI is an independent predictor for OS for overweight and obese I patients, specifically for those treated with Bevacizumab. Patients who are overweight or obese (group I) may be a target group for lifestyle and nutrition advice to improve OS with TT.
Multi‐Species Multi‐Channel (MSMC): An Ab Initio‐based Parallel Thermodynamic and Kinetic Code for Complex Chemical Systems
Authors: Duong Minh V. , Nguyen Hieu T. , Truong Nghia , Le Thong N.‐M. , Huynh Lam K. 
Published: July 2015

ABSTRACTMulti‐Species Multi‐Channel (MSMC) is an ab initio parallel program to calculate thermodynamic quantities (e.g., , , , and , time‐dependent species profiles, and rate coefficients as functions of temperature and pressure for complex chemical reaction systems, which consist of multiple stable species and multiple reaction channels interconnecting them. Thermodynamic properties of the species involved are calculated using statistical mechanics with molecular information from electronic structure calculations. Temperature‐ and pressure‐dependent behaviors are rigorously characterized within the eigenpair master equation/Rice–Ramsperger–Kassel–Marcus (ME/RRKM) framework. Corrections, e.g., for hindered internal rotation and tunneling treatment, are included. With the implementation of an ultra‐high precision package and rigorous matrix setup, MSMC is able to correctly mimic real behaviors of different types of chemical systems. Different eigenpair‐based approaches to extract phenomenological/macroscopic rate coefficients are implemented for different applications. Moreover, a friendly and platform‐independent graphical‐user‐interface (GUI) is provided to facilitate the use of MSMC and the pre‐/postcalculation data visualization/analysis on the fly. The program can be freely downloaded at https://sites.google.com/site/msmccode/.
Anti‐inflammatory effect of hospital‐grade hochuekkito extract, a traditional Japanese herbal medicine, on methotrexate‐induced intestinal mucositis in mice
Authors: Sekiya Michiko , Kiyohara Hiroaki , Maruyama Hiroko , Tsukada Naoya , Yasuda Ayano , Nagai Takayuki , Yamada Haruki 
Published: July 2015

ABSTRACTAimHospital‐grade extract of hochuekkito, a traditional Japanese herbal (Kampo) formula, has been found to be clinically effective against mucositis induced by anticancer drugs, but the mechanism of action of this formula has not been clarified as yet. The aim of this study was to investigate the anti‐inflammatory effects of hochuekkito against chemotherapy‐induced mucositis in a mice model.MethodsMucositis in jejunum was induced by i.p. injection with methotrexate (MTX, 100 mg/kg) in BALB/c mice. Hospital‐grade hochuekkito extract (TJ‐41) was administered in oral doses (1 g/kg/day).ResultsThe tissue damage score of jejunum was improved in early stage mucositis (at day 3 after one‐off MTX injection). Expression of tumor necrosis factor (
TNF
)‐α and interleukin‐1β mRNA in jejunum of MTX‐treated mice was downregulated by TJ‐4 at day 2 and 3 after one‐off MTX injection. mRNA expression of regulatory adaptor molecules such as interleukin‐1 receptor‐associated kinase‐3 (
IRAK‐M
), single immunoglobulin and toll‐interleukin 1 receptor domain (
SIGIRR
), tumor necrosis factor‐α‐induced protein 3 (
A20
) and cylindromatosis (
Cyld) was significantly enhanced at day 1 of oral TJ‐41 treatment, but these changes were not observed on MTX treatment alone.Conclusions
TJ‐41 reduces intestinal mucositis induced by MTX. TJ‐41 induces specific expression of regulatory adaptor molecules, such as IRAK‐M, SIGIRR, A20 and Cyld, in the MyD88‐associated inflammatory signal cascade under conditions of inflammation, and this phenomenon is postulated to be associated with the anti‐inflammatory effect of the formula on intestinal mucositis.
Clinical use of amyloid‐positron emission tomography neuroimaging: Practical and bioethical considerations
Authors: Witte Michael M. , Foster Norman L. , Fleisher Adam S. , Williams Monique M. , Quaid Kimberly , Wasserman Michael , Hunt Gail , Roberts J. Scott , Rabinovici Gil D. , Levenson James L. , Hake Ann Marie , Hunter Craig A. , Van Campen Luann E. , Pontecorvo Michael J. , Hochstetler Helen M. , Tabas Linda B. , Trzepacz Paula T. 
Published: July 2015

AbstractUntil recently, estimation of β‐amyloid plaque density as a key element for identifying Alzheimer's disease (AD) pathology as the cause of cognitive impairment was only possible at autopsy. Now with amyloid‐positron emission tomography (amyloid‐PET) neuroimaging, this AD hallmark can be detected antemortem. Practitioners and patients need to better understand potential diagnostic benefits and limitations of amyloid‐PET and the complex practical, ethical, and social implications surrounding this new technology. To complement the practical considerations, Eli Lilly and Company sponsored a Bioethics Advisory Board to discuss ethical issues that might arise from clinical use of amyloid‐PET neuroimaging with patients being evaluated for causes of cognitive decline. To best address the multifaceted issues associated with amyloid‐PET neuroimaging, we recommend this technology be used only by experienced imaging and treating physicians in appropriately selected patients and only in the context of a comprehensive clinical evaluation with adequate explanations before and after the scan.
BioCluster: Tool for Identification and Clustering of Enterobacteriaceae Based on Biochemical Data
Authors: Abdullah Ahmed , Sabbir Alam S.M. , Sultana Munawar , Hossain M. Anwar 
Published: July 2015

Abstract
Presumptive identification of different Enterobacteriaceae species is routinely achieved based on biochemical properties. Traditional practice includes manual comparison of each biochemical property of the unknown sample with known reference samples and inference of its identity based on the maximum similarity pattern with the known samples. This process is labor-intensive, time-consuming, error-prone, and subjective. Therefore, automation of sorting and similarity in calculation would be advantageous. Here we present a MATLAB-based graphical user interface (GUI) tool named BioCluster. This tool was designed for automated clustering and identification of Enterobacteriaceae based on biochemical test results. In this tool, we used two types of algorithms, i.e., traditional hierarchical clustering (HC) and the Improved Hierarchical Clustering (IHC), a modified algorithm that was developed specifically for the clustering and identification of Enterobacteriaceae species. IHC takes into account the variability in result of 1–47 biochemical tests within this Enterobacteriaceae family. This tool also provides different options to optimize the clustering in a user-friendly way. Using computer-generated synthetic data and some real data, we have demonstrated that BioCluster has high accuracy in clustering and identifying enterobacterial species based on biochemical test data. This tool can be freely downloaded at http://microbialgen.du.ac.bd/biocluster/.
Dementia incidence declined in African‐Americans but not in Yoruba
Authors: Gao Sujuan , Ogunniyi Adesola , Hall Kathleen S. , Baiyewu Olusegun , Unverzagt Frederick W. , Lane Kathleen A. , Murrell Jill R. , Gureje Oye , Hake Ann M. , Hendrie Hugh C. 
Published: July 2015

AbstractIntroductionTo compare dementia incidence of African‐American and Yoruba cohorts aged ≥70 years enrolled in 1992 and 2001.MethodsAfrican‐Americans residing in Indianapolis and Yoruba in Ibadan, Nigeria without dementia were enrolled in 1992 and 2001 and evaluated every 2–3 years until 2009. The cohorts consist of 1440 African‐Americans, 1774 Yoruba in 1992 and 1835 African‐Americans and 1895 Yoruba in the 2001 cohorts aged ≥70 years.ResultsIn African‐Americans, dementia and Alzheimer's disease (AD) incidence rates were significantly lower in 2001 than 1992 for all age groups except the oldest group. The overall standardized annual dementia incidence rates were 3.6% (95% confidence interval [CI], 3.2%–4.1%) in the 1992 cohort and 1.4% (95% CI, 1.2%–1.7%) in the 2001 cohort. There was no significant difference in dementia or AD incidence between the Yoruba cohorts.DiscussionFuture research is needed to explore the reasons for the differential changes in incidence rates in these two populations.
Linking business strategy to service failures and financial performance: Empirical evidence from the U.S. domestic airline industry
Authors: Mellat‐Parast Mahour , Golmohammadi Davood , McFadden Kathleen L. , Miller Jason W. 
Published: July 2015

AbstractDeveloping an understanding of the relationship between service quality and profitability is of central importance to operations management scholars. In this study we seek to reconcile inconsistencies between extant theory and empirical findings regarding the relationship between service quality and profitability in the airline industry. More specifically, we draw on theories from strategic management, operations strategy, and economics to explain why the relationship between measures of service quality and profitability will be moderated by an airline's competitive strategy. We test our hypotheses by fitting mixed‐effects models to longitudinal data obtained from several governmental databases in the context of the U.S. domestic airline industry. We find that airline strategy moderates the relationship between some service failures and profitability. Specifically, we find that mishandled baggage and customer complaints more negatively affect the profitability of focused than non‐focused airlines. We also find the relationship between arrival delays on profitability is universally negative for focused airlines, but displays an inverted U‐shaped relationship for non‐focused airlines. Our findings provide significant contributions to the existing body of knowledge in service quality and operations strategy. We further outline the implications of these findings for practice and future research.
“I’m not hoarding, I’m just stocking up before the hoarders get here.”
Authors: Sterman John D. , Dogan Gokhan 
Published: July 2015

AbstractWhen suppliers are unable to fill orders, delivery delays increase and customers receive less than they desire. Customers often respond by seeking larger safety stocks (hoarding) and by ordering more than they need to meet demand (phantom ordering). Such actions cause still longer delivery times, creating positive feedbacks that intensify scarcity and destabilize supply chains. Hoarding and phantom ordering can be rational when customers compete for limited supply in the presence of uncertainty or capacity constraints. But they may also be behavioral and emotional responses to scarcity. To address this question we extend Croson et al.’s (2014) experimental study with the Beer Distribution Game. Hoarding and phantom ordering are never rational in the experiment because there is no horizontal competition, randomness, or capacity constraint; further, customer demand is constant and participants have common knowledge of that fact. Nevertheless 22% of participants place orders more than 25 times greater than the known, constant demand. We generalize the ordering heuristic used in prior research to include the possibility of endogenous hoarding and phantom ordering. Estimation results strongly support the hypothesis, with hoarding and phantom ordering particularly strong for the outliers who placed extremely large orders. We discuss psychiatric and neuroanatomical evidence showing that environmental stressors can trigger the impulse to hoard, overwhelming rational decision‐making. We speculate that stressors such as large orders, backlogs or late deliveries trigger hoarding and phantom ordering for some participants even though these behaviors are irrational. We discuss implications for supply chain design and behavioral operations research.
How analytic reasoning style and global thinking relate to understanding stocks and flows
Authors: Weinhardt Justin M. , Hendijani Rosa , Harman Jason L. , Steel Piers , Gonzalez Cleotilde 
Published: July 2015

AbstractUnderstanding stock‐flow relationships is fundamental to the management of operational systems. In their most basic form, stock‐flow systems consist of resources that accumulate and flows that change their level. Managing stock‐flow systems is an indispensable part of operations management, including supply chain, inventory, and capacity planning. Previous studies have shown that most people, even experts and well‐educated individuals, make persistent errors when inferring the behavior of accumulation (i.e., stock) over time. However, little is known about what individual characteristics make a decision maker better or worse at understanding stock‐flows. In this paper, we report the results of investigating the relationship between analytical‐intuitive thinking and global‐local processing on performance in a simple stock‐flow problem.We find that individuals with an analytical thinking style, rather than an intuitive one, perform significantly better on a stock‐flow problem; whereas individuals with a global, rather than a local, thinking style do not necessarily perform better. However, even individuals who exhibit analytical thinking have a poor understanding of stock‐flow problems. Analytical thinking may be related to understanding stock and flows, but more work is needed to better understand what cognitive abilities are required to solve these problems.
Cost‐sharing in directed networks: Experimental study of equilibrium choice and system dynamics
Authors: Liu Caiyun , Mak Vincent , Rapoport Amnon 
Published: July 2015

AbstractThis study reports the results of an experiment on directed networks with positive externalities induced by cost‐sharing. Subjects participated in a network game in which they had to choose between private and public transportations. If a player chose public transportation, then she shared the travel cost equally with other players making the same choice, whereas if she chose private transportation, then her travel cost was fixed. Travel costs on the private route were manipulated across the two experimental conditions. In one condition, these costs were homogeneous among players; in the other condition, they were heterogeneous among players and only privately known. We found that half (none) of the player groups in the homogeneous (heterogeneous) condition converged toward the efficient equilibrium. Examination of the system dynamics shows that convergence toward efficiency was facilitated by: (1) the existence of an intermediate equilibrium choice; and (2) strategic teaching by which a farsighted player chooses strategies with poor short‐term payoff in order to shift group decisions to the efficient equilibrium and thereby increase her own long‐term benefit.